BACKGROUND Mesonephric-like adenocarcinoma(MLA)is a rare and highly malignant disease that occurs in the uterine body or ovaries.We report a case of a MLA that was considered to have originated in the fallopian tube a...BACKGROUND Mesonephric-like adenocarcinoma(MLA)is a rare and highly malignant disease that occurs in the uterine body or ovaries.We report a case of a MLA that was considered to have originated in the fallopian tube and presented with malignant peritonitis.CASE SUMMARY A 57-year-old female presented with a chief complaint of abdominal pain that began 2 months prior.Cancerous peritonitis was suspected.During exploratory laparoscopy,the right fallopian tube was found to be enlarged,with widespread disseminated lesions extending from the pelvic cavity to the upper abdomen.Histopathological examination of the peritoneal tissue obtained by biopsy showed tumor cells with a high nuclear/cellular ratio and proliferation of papillary tubular to pedunculated solid nests.Immunohistochemical testing was positive for GATA-binding protein 3,thyroid transcription factor 1,cluster of differentiation 10,and paired box protein-8,and negative for estrogen receptor,Wilms’tumor 1,and wild-type p53,leading to the diagnosis of MLA.Subsequently,debulking surgery was performed,and no macroscopic residual tumors were identified.The pathological diagnosis was right tubal carcinoma,mesonephric adenocarcinoma(International Federation of Gynecology and Obstetrics stage IIIC),and pT3cNXM0.Adjuvant chemotherapy was administered postoperatively;however,recurrence was noted,and the patient died 1 year and 6 months after the initial treatment.CONCLUSION MLA is a very rare disease with poor prognosis.Further studies are necessary to identify effective treatment options.展开更多
Tumor cell-intrinsic programmed death-ligand 1(PD-L1)signals mediate tumor initiation,progression and metastasis,but their effects in ameloblastoma(AM)have not been reported.In this comprehensive study,we observed mar...Tumor cell-intrinsic programmed death-ligand 1(PD-L1)signals mediate tumor initiation,progression and metastasis,but their effects in ameloblastoma(AM)have not been reported.In this comprehensive study,we observed marked upregulation of PD-L1 in AM tissues and revealed the robust correlation between elevated PD-L1 expression and increased tumor growth and recurrence rates.Notably,we found that PD-L1 overexpression markedly increased self-renewal capacity and promoted tumorigenic processes and invasion in hTERT^(+)-AM cells,whereas genetic ablation of PD-L1 exerted opposing inhibitory effects.By performing highresolution single-cell profiling and thorough immunohistochemical analyses in AM patients,we delineated the intricate cellular landscape and elucidated the mechanisms underlying the aggressive phenotype and unfavorable prognosis of these tumors.Our findings revealed that hTERT^(+)-AM cells with upregulated PD-L1 expression exhibit increased proliferative potential and stem-like attributes and undergo partial epithelial-mesenchymal transition.This phenotypic shift is induced by the activation of the PI3KAKT-mTOR signaling axis;thus,this study revealed a crucial regulatory mechanism that fuels tumor growth and recurrence.Importantly,targeted inhibition of the PD-L1-PI3K-AKT-mTOR signaling axis significantly suppressed the growth of AM patientderived tumor organoids,highlighting the potential of PD-L1 blockade as a promising therapeutic approach for AM.展开更多
在法医学检案中,经常要对尸体上的损伤进行检验以确定生前伤或死后伤,并要鉴定损伤时间.损伤超过8小时者一般用常规组织学方法可以解决,但损伤后经过时间较短,单用组织学方法不能解决,如利用酶活性反应方法和利用在组织内细胞内进行特...在法医学检案中,经常要对尸体上的损伤进行检验以确定生前伤或死后伤,并要鉴定损伤时间.损伤超过8小时者一般用常规组织学方法可以解决,但损伤后经过时间较短,单用组织学方法不能解决,如利用酶活性反应方法和利用在组织内细胞内进行特异、灵敏、稳定的抗原抗体反应,可以较准确鉴定损伤时间.Perper J. A. Raek Allio、Tanaka、Fatteh等报导用组织化学方法鉴定损伤时间,祝家镇、刘世仓教授近年来也有报道,但用免疫组化学方法来鉴定损伤后早期时间,就作者所知,国内、外未见报道,而FN在创伤愈合过程中的作用国内外已有报道.展开更多
The immunohistochemical localization of IAA and the comparison of their relative levels were carried out for the first time in the anthers of Nongken 58S and its wild type Nongken 58 (Oryza sativa subsp. japonica) af...The immunohistochemical localization of IAA and the comparison of their relative levels were carried out for the first time in the anthers of Nongken 58S and its wild type Nongken 58 (Oryza sativa subsp. japonica) after long_day and short_day treatments. The distribution of free_IAA in anthers and its dynamic variation could be reflected by this method. The results showed that the IAA level in the anthers of Nongken 58S after long_day treatment was much lower than that in short_day_treated Nongken 58S and those in wild type Nongken 58 in five stages from pistil and stamen primordia formation to late uninucleate stage. The possible reasons for IAA deficiency in Nongken 58S_LD anthers and its relationship with fertility alteration were also discussed.展开更多
AIM: To improve the clinical diagnosis and recognition of hepatic epithelioid angiomyolipoma(HEAML).METHODS: Four cases of primary HEAML were confirmed based on the pathology archive system in our hospital from Januar...AIM: To improve the clinical diagnosis and recognition of hepatic epithelioid angiomyolipoma(HEAML).METHODS: Four cases of primary HEAML were confirmed based on the pathology archive system in our hospital from January 2009 to November 2015. The general state, clinical symptoms, imaging manifestations, histological results and immunohistochemistry of these patients were retrospectively reviewed and analyzed. Studies of HEAML published in the last 15 years were collected from Pub Med and MEDLINE to summarize the clinical symptoms, imaging characteristics, pathological features and management of HEAML.RESULTS: Four cases of primary HEAML were retrieved from our archives. These included three female patients and one male patient, with a mean age of 41.8 ± 11.5 years(ranging from 31 to 56 years). The meantumor size was 7.3 ± 5.5 cm(ranging from 3.0 to 15 cm). In the contrast-enhanced imaging, the tumor was obviously enhanced in the arterial phase, but enhanced continuously or exhibited a slow-density masse during the venous and delayed phases. Histologically, the tumors mainly consisted of epithelioid cells that comprised approximately 95% of the total neoplastic mass. Although no metastases occurred in our patients, pathological studies revealed necrosis, mitotic figures and liver invasion in two patients, which indicates aggressive behavior. Immunohistochemical staining revealed that human melanoma black 45(HMB-45) and Melan-A were positive in 4 cases. We only identified 81 cases with primary HEAML, including our present patients, from 26 articles available from Pub Med and MEDLINE. The majority of the papers were published as case reports. Only 5(5/75, 6%) cases were associated with tuberous sclerosis complex(TSC). More than half(35/66) were discovered incidentally upon physical examination. Approximately 65%(22/34) of the patients were misdiagnosed with HCC or other tumors before surgery. Approximately 10%(8/81) of the patients with HEAML had recurrence or metastasis after surgery, which was a very high and alarming rate.CONCLUSION: HEAML is a very rare primary hepatic tumor that is often misdiagnosed before surgery. Patients should be followed closely after surgery because of its malignant potential.展开更多
Background: Esophageal squamous cell carcinoma(ESCC) is an aggressive malignancy, with a high incidence and poor prognosis. In the past several decades, hundreds of proteins have been reported to be associated with th...Background: Esophageal squamous cell carcinoma(ESCC) is an aggressive malignancy, with a high incidence and poor prognosis. In the past several decades, hundreds of proteins have been reported to be associated with the prognosis of ESCC, but none has been widely accepted to guide clinical care. This study aimed to identify proteins with great potential for predicting prognosis of ESCC.Methods: We conducted a systematic review on immunohistochemical(IHC) prognostic markers of ESCC according to the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA) Guidelines. Literature related to IHC prognostic markers of ESCC were searched from PubMed, Embase, Web of Science, and Cochrane Library until January 30 th, 2017. The risk of bias of these original studies was evaluated using the Quality in Prognosis Studies(QUIPS) tool.Results: We identified 11 emerging IHC markers with reproducible results, including eight markers [epidermal growth factor receptor(EGFR), Cyclin D1, vascular endothelial growth factor(VEGF), Survivin, Podoplanin, Fascin,phosphorylated mammalian target of rapamycin(p-mTOR), and pyruvate kinase M2(PKM2)] indicating unfavorable prognosis and 3 markers(P27, P16, and E-cadherin) indicating favorable prognosis of ESCC.Conclusion: Strong evidence supports that these 11 emerging IHC markers or their combinations may be useful in predicting prognosis and aiding personalized therapy decision-making for ESCC patients.展开更多
AIM To further study the role of bcl 2 protein expression in gastric carcinogenesis and tumor progression. METHODS Using immunohistochemical staining, the bcl 2 protein expression in 50 cases of gastric carcinoma...AIM To further study the role of bcl 2 protein expression in gastric carcinogenesis and tumor progression. METHODS Using immunohistochemical staining, the bcl 2 protein expression in 50 cases of gastric carcinoma and its relation to clinical status and pathomorphological parameters were observed. RESULTS Forty one (82%) cases were positive for bcl 2 protein staining which was located in the cytoplasm and nuclear membrane of tumor cells. The rate of bcl 2 protein expression was not correlated with the patient, sex, tumor size, lymph node status or clinical stages ( P >0 05). It was strongly associated with intestinal type tumors and poorly differentiated tumors ( P <0 05 and P <0 01). CONCLUSION Aberrant bcl 2 protein expression appears to be specifically associated with development of intestinal type gastric carcinoma, bcl 2 protein expression might play an important role in the early development/promotion and phenotypic differentiation of gastric carcinomas, but not in tumor progression.展开更多
AIM: To retrospectively evaluate the computed tomography (CT)/magnetic resonance imaging (MRI) imaging features of epithelioid angiomyolipoma of the liver (Epi-HAML), with pathology as a reference. METHODS: Th...AIM: To retrospectively evaluate the computed tomography (CT)/magnetic resonance imaging (MRI) imaging features of epithelioid angiomyolipoma of the liver (Epi-HAML), with pathology as a reference. METHODS: The CT/MRI findings (number, diameter, lobar location, and appearance of lesions) in a series of 10 patients with 12 pathologically proven epithelioid angiomyolipomas of the liver were retrospectively analyzed. The imaging features, including attenuation/ signal intensity characteristics, presence of fat, hypervascular, outer rim, and vessels within lesion, were evaluated and compared with that of non-Epi- HAML in 11 patients (13 lesions). The Fisher exact test was used to compare difference in probability of imaging features between the two types. RESULTS: For 21 patients, CT images of 15 patients and MR images of six patients were available. No patient underwent two examinations. For the 15 patients with a CT scan, all HAML lesions in the two groups (10 Epi-HAML and seven non-Epi-HAML) manifested as hypoattenuation. For the six patients with MRI, all lesions (two Epi-HAML and six non-Epi- HAML) were hypointense on TlWI (fat suppression) and hyperintense on T2WI. There were 10 non-Epi-HAML, but only two Epi-HAML lesions showed the presence of fat, which significantly different between the two types (P = 0.005). On the dynamic contrast enhancement (DCE) imaging, eight Epi-HAML, and 13 non-Epi lesions manifested as hypervascular. Punctate or curved vessels were displayed in 10 Epi-HAML as well as in nine non- Epi lesions and outer rim enhancement could be found with eight Epi-HAML as well as six non-Epi lesions. CONCLUSION: Little or no presence of adipose tissue was found to be an imaging feature of Epi- HAML, compared with the non-Epi type. In addition, hypervascularity with opacification of central punctiform or filiform vessels on DCE would be a characteristic enhancement pattern for Epi-HAML.展开更多
BACKGROUND Intrahepatic sarcomatoid chonalgiocarcinoma(s-CCC) is an extremely rare disease, accounting for less than 1% of hepatobiliary system malignancies, and its pathophysiology is not well known. On the hypothesi...BACKGROUND Intrahepatic sarcomatoid chonalgiocarcinoma(s-CCC) is an extremely rare disease, accounting for less than 1% of hepatobiliary system malignancies, and its pathophysiology is not well known. On the hypothesis that its clinical, serologic,or radiologic diagnosis are not fully understood and its prognosis is poor, we investigated the distinguishing features of s-CCC compared with those of intrahepatic bile duct adenocarcinoma [cholangiocellular carcinoma(CCC)] in patients from a single center.AIM To analyze the clinical, serologic, imaging, and histopathologic characteristics of intrahepatic s-CCC patients diagnosed in a single center.METHODS The clinical, serologic, imaging, and histopathologic features of 227 patients diagnosed with intrahepatic cholangiocarcinoma(IHCC) in a single medical center during the last 17 years were analyzed. The characteristics of 11 patients with s-CCC were compared with those of 216 patients with CCC.RESULTS The number of patients with s-CCC who presented fever and abdominal pain and past history of chronic viral hepatitis or liver cirrhosis(LC) was higher than that of patients with CCC. In imaging studies, patients with s-CCC showed relatively aggressive features. However, no clear distinction was observed between s-CCC and CCC based on other clinical, serologic or radiologic examination results. An accurate diagnosis could be made only via a histopathologic examination through immunohistochemical staining. The clinical course of s-CCC was generally aggressive, and patients had a relatively poor prognosis.CONCLUSION In patients with s-CCC, early diagnosis through biopsy and aggressive treatment,including surgical resection, are important.展开更多
AIM:To investigate semaphorin 4D(Sema4D)and hypoxia-inducible factor-1α(HIF-1α)expression in colorectal carcinoma and evaluate their clinicopathological and prognostic significance.METHODS:Eighty-six curatively rese...AIM:To investigate semaphorin 4D(Sema4D)and hypoxia-inducible factor-1α(HIF-1α)expression in colorectal carcinoma and evaluate their clinicopathological and prognostic significance.METHODS:Eighty-six curatively resected colorectal carcinoma patients at different stages of disease were randomly selected from the group of patients who underwent surgery,and none of them received preoperative radiochemotherapy.Normal proximal adjacent bowel tissue,which served as an internal control,was obtained from 52 randomly selected patients.Immunohistochemistry was performed to analyze the expression of Sema4D and the tumor angiogenesisrelated protein HIF-1αin normal colorectal tissues and colorectal carcinoma tissues.The relationships between the expression and clinical characters and prognosis were analyzed.RESULTS:HIF-1αand Sema4D were positively expressed in 58%and 60%of colorectal carcinoma tissues,respectively.Significantly lower expression levels were observed in normal mucosa(8%and 12%,respectively).HIF-1αand Sema4D expression was closely correlated with histological tumor type,tumornode-metastasis(TNM)stage,and lymphatic metastasis(P<0.05),but not with age or tumor size(P>0.05).HIF-1αand Sema4D protein expression was significantly correlated with prognosis of colorectal carcinoma,as determined by Spearman rank correlation analysis(r=0.567;P<0.01).Multivariate Cox analysis revealed that only Sema4D expression played a significant role in predicting patient prognosis(P<0.05).CONCLUSION:These findings suggest that HIF-1αand Sema4D expression correlates with histological tumor type,TNM stage,and lymphatic metastasis in colorectal carcinoma and that Sema4D is a prognostic indicator of colorectal carcinoma.展开更多
Objective:To explore the mechanism of Buyang Huanwu Tang (补阳还五汤 Decoction Invigorating Yang for Recuperation) combined with bone marrow mesenchymal stem cells (MSCs) transplantation in protecting nerves of cerebr...Objective:To explore the mechanism of Buyang Huanwu Tang (补阳还五汤 Decoction Invigorating Yang for Recuperation) combined with bone marrow mesenchymal stem cells (MSCs) transplantation in protecting nerves of cerebral ischemic injury. Methods: Local cerebral ischemia-reperfusion rat model was established with modified Zea-Longa thread-occlusion method, and MSCs were injected into the caudal vein, and Buyang Huanwu Tang(补阳还五汤)was administrated. Vascular endothelial growth factor (VEGF) and Ki-67 expression in the ischemic side of the brain in the cerebral ischemic-reperfusion rat were detected with immuno-histochemical staining method. Results: VEGF and Ki-67 expressions were significantly up-regulated in the MSCs group and the combination group, with significant differences as compared with the model group and the sham operation group (P<0.05), and with the most strongest effect in the combination group. Conclusion: Buyang Huanwu Tang(补阳还五汤)combined with MSCs transplantation repairs the injured blood vessels and lesion tissues possibly by up-regulation of VEGF and Ki-67 expression.展开更多
Hepatocellular carcinoma(HCC) accounts for over 90% of all primary liver cancers. With an ever increasing incidence trend year by year,it has become the third most common cause of death from cancer worldwide. Hepatic ...Hepatocellular carcinoma(HCC) accounts for over 90% of all primary liver cancers. With an ever increasing incidence trend year by year,it has become the third most common cause of death from cancer worldwide. Hepatic resection is generally considered to be one of the most effective therapies for HCC patients,however,there is a high risk of recurrence in postoperativeHCC. In clinical practice,there exists an urgent need for valid prognostic markers to identify patients with prognosis,hence the importance of studies on prognostic markers in improving the prediction of HCC prognosis. This review focuses on the most promising immunohistochemical prognostic markers in predicting the postoperative survival of HCC patients.展开更多
AIM:To clarify the clinicopathologic significance of COX-2 expression in human colorectal cancer.METHODS:A total of 128 surgically resected colorectal cancer specimens were immunohistochemically analyzed with the use ...AIM:To clarify the clinicopathologic significance of COX-2 expression in human colorectal cancer.METHODS:A total of 128 surgically resected colorectal cancer specimens were immunohistochemically analyzed with the use of anti-COX-2,anti-VEGF and anti-MMP-2 antibodies.The relationship between the cyclooxygenase-2 expression in primary lesions of colorectal cancer and clinicopathoiogic parameters was evaluated by chi-square test.RESULTS:Among 128 cases of colorectal cancer,87(67.9%)were positive for cyclooxygenase-2.The expression of cyclooxygenase-2 was significantly correlated with the depth of invasion,stage of disease,and metastasis(lymph node and liver).Patients in T3-T4,stagesⅢ-Ⅳand with metastasis had much higher expression of cyclooxygenase-2 than ones in T1-T2,stagesⅠ-Ⅱand without metastasis(P<0.05).Among 45 cases of colorectal cancer with lymph node metastasis,the COX-2-positive rate was 86.7%(39/45)for primary lesions and diffuse cytoplasmic staining for COX-2 protein was detected in cancer cells in 100%of metastatic lesions of the lymph nodes.VEGF expression was detected in 49 tumors(38.3%),and VEGF expression was closely correlated with COX-2 expression.The positive expression rate of VEGF(81.6%)in the cyclooxygenase-2-positive group was higher than that in the cyclooxygenase-2-negative group(18.4%,P<0.05).MMP-2 expression was detected in 88 tumors(68.8%),and MMP-2 expression was closely correlated with COX-2 expression.The positive expression rate of MMP-2(79.6%)in the positive COX-2 group was higher than that in the negative COX-2 group(20.4%,P<0.05).CONCLUSION:Cyclooxygenase-2 may be associated with tumor progression by modulating the angiogenesis and cancer cell motility and invasive potential in colorectal cancer and it can be used as a possible biomarker.展开更多
Objective:To investigate the expression and significance of MMP-3 in synovium of knee joint at different stage in osteoarthritis(OA)patients.Methods:Knee synovial tissue were collected in90 OA patients(the OA group).P...Objective:To investigate the expression and significance of MMP-3 in synovium of knee joint at different stage in osteoarthritis(OA)patients.Methods:Knee synovial tissue were collected in90 OA patients(the OA group).Patients in the OA group was divided into 3 subgroups:gradeⅠsubgroup(n=30),gradeⅡsubgroup(n=30),gradeⅢsubgroup(n=30).Thirty patients served as control group,lmmunohistochemical assay was used to detect the expression of MMP-3 protein in the knee synovial tissue.Results:MMP-3 protein was detected in all knee synovial tissue.The expression of MMP-3 protein in the OA group was significantly higher that in the normal synovium(P<0.05),and the MMP-3 protein was mainly located in the cytoplasm.There was significant difference in the expression of MMP-3 protein between the gradeⅢsubgroup and the gradeⅠ,gradeⅡsubgroups(all P<0.05).The expression of MMP-3 protein was positively related to the severity of OA(r=0.912,P<0.05).Conclusions:The expression of MMP-3 protein are closely related to pathogenic mechanism of OA.It may be an important indicator of early diagnosis and the activity of the disease of osteoarthritis.展开更多
Cytomegalovirus(CMV) infection is common in humans.The virus then enters a "latency phase" and can reactivate to different stimuli such as immunosuppression.The clinical significance of CMV infection in infl...Cytomegalovirus(CMV) infection is common in humans.The virus then enters a "latency phase" and can reactivate to different stimuli such as immunosuppression.The clinical significance of CMV infection in inflammatory bowel disease is different in Crohn's disease(CD) and ulcerative colitis(UC).CMV does not interfere in the clinical course of CD.However,CMV reactivation is frequent in severe or steroid-resistant UC.It is not known whether the virus exacerbates the disease or simply appears as a bystander of a severe disease.Different methods are used to diagnose CMV colitis.Diagnosis is classically based on histopathological identification of viral-infected cells or CMV antigens in biopsied tissues using haematoxylin-eosin or immunohistochemistry,other tests on blood or tissue samples are currently being investigated.Polymerase chain reaction performed in colonic mucosa has a high sensitivity and a positive result could be associated with a worse prognosis disease;further studies are needed to determine the most appropriate strategy with positive CMV-DNA in colonic mucosa.Specific endoscopic features have not been described in active UC and CMV infection.CMV colitis is usually treated with ganciclovir for several weeks,there are different opinions about whether or not to stop immunosuppressive therapy.Other antiviral drugs may be used.Multicenter controlled studies would needed to determine which subgroup of UC patients would benefit from early antiviral treatment.展开更多
AIM: To investigate the expression of Neurensin-2 (NRSN2) in hepatocellular carcinoma (HCC) and its prognostic values in predicting survival. METHODS: The expression and prognostic significance of NRSN2 in HCC w...AIM: To investigate the expression of Neurensin-2 (NRSN2) in hepatocellular carcinoma (HCC) and its prognostic values in predicting survival. METHODS: The expression and prognostic significance of NRSN2 in HCC was examined by performing immunohistochemical analysis using a total of 110 HCC clinical tissue samples, and Western blotting analysis to further confirm the result. RESULTS: Decreased NRSN2 expression was shown in 70.9% cases. Loss of NRSN2 expression in HCC was significantly related to tumor size (P = 0.006). Larger tumor size was related to negative expression of NRSN2. Patients showing negative NRSN2 expression had a significantly shorter overall survival than those with positive expression (P = 0.008). Multivariate Cox regression analysis indicated that NRSN2 expression level was an independent factor of survival (P = 0.013). Western blotting analysis further confirmed decreased expression of NRSN2 in tumor tissues compared with non-tumorous tissues. CONCLUSION: Our study indicated that NRSIV2 could be a tumor suppressor gene for HCC and a candidate biomarker for long-term survival in HCC.展开更多
AIM: To study the expressions of p27^kip1 protein and p27mRNA, the hypermethylation of p27^kip1 and the relation between them in various stages of hepatocarcinogenesis. METHODS: p27 protein and p27mRNA were detected...AIM: To study the expressions of p27^kip1 protein and p27mRNA, the hypermethylation of p27^kip1 and the relation between them in various stages of hepatocarcinogenesis. METHODS: p27 protein and p27mRNA were detected by immunohistochemical staining and in situ hybridization respectively in 68 cases of normal liver, liver cirrhosis, pericancerous cirrhosis and hepatocellular carcinoma (HCC). The hypermethylation of p27^kip1 was detected by methylation-specific PCR (MSP) in 44 cases of normal liver, liver cirrhosis, and HCC. RESULTS: The positive rate of p27 protein was 66.7% (4/6) in normal liver, 60.0% (6/10) in liver cirrhosis, 50.0% (12/24) in pericancerous cirrhosis and 21.4% (6/28) in HCC. There were no statistical differences in normal liver, liver cirrhosis and pericancerous cirrhosis, but the positive rate of p27 protein significantly decreased in HCC compared to that in the other groups (P = 0.006, %2 = 7.664). The positive rate of p27^kip1 mRNA was 83.3% (5/6) in normal liver, 70.0% (7/10) in liver cirrhosis, 75.0% (18/24) in pericancerous cirrhosis and 25.0% (7/28) in HCC. There were no statistical differences in normal liver, liver cirrhosis and pericancerous cirrhosis, but the positive rate of p27^kip1 mRNA also significantly decreased in HCC compared to that in the other groups (P = 0.000, %2 = 16.600). In addition, there was a significant correlation between the expression of p27 protein and p27mRNA in the integrated group of normal liver and liver cirrhosis. However, no significant correlation was found between pericancerous cirrhosis and HCC. Using MSP, we found that 1 HCC in 44 cases (including 6 cases of normal liver, 10 cases of liver cirrhosis and 28 cases of HCC) was methylated, whose p27 protein and p27mRNA were negative. CONCLUSION: The reduction or loss of p27 protein and p27mRNA are potentially involved in hepatocarcinogenesis. The hypermethylation of p27 might lead to the loss of p27mRNA transcription.展开更多
Objective: To study the relationship between lymph node metastases in esophageal carcinoma and its prognosis. Methods: We obtained 1500 resected lymph nodes from the specimen of 86 patients with resected esophageal ca...Objective: To study the relationship between lymph node metastases in esophageal carcinoma and its prognosis. Methods: We obtained 1500 resected lymph nodes from the specimen of 86 patients with resected esophageal carcinoma and checked these lymph nodes by routine histopathology. Additiionally, frozen tissue sections of 540 lymph nodes classified as tumor-free by routine histopathology were screened for micrometastases by immunohistology with the monoclonal antibody Ber-EP4. Results: Forty-two patients (49%) had pN0 disease, and 61 patients (71%) had lymph node micrometastases detected by immunohistochemistry, skip metastases detected by routine histopathology were present in 26%(11/42) of pN0 and 41%(18/44) of pN1 patients. Skipping of micrometastases detected by immunohistochemistry was found in 71%(61/86). Twenty-six of 42 patients (62%) with tumor staged as pN0 and 35 of 44 patients (80%) with stage pN1 had nodal micrometastasis. The presence of micrometastases was associated with a significantly decreased relapse-free time and overall survival (P<0.0001 and P=0.004, respectively). Conclusion: Lymph node skip metastases are a frequent event in esophageal carcinoma. Extensive lymph node sampling, in conjunction with immunohistochemical detection, will lead to accurate staging and prognosis.展开更多
文摘BACKGROUND Mesonephric-like adenocarcinoma(MLA)is a rare and highly malignant disease that occurs in the uterine body or ovaries.We report a case of a MLA that was considered to have originated in the fallopian tube and presented with malignant peritonitis.CASE SUMMARY A 57-year-old female presented with a chief complaint of abdominal pain that began 2 months prior.Cancerous peritonitis was suspected.During exploratory laparoscopy,the right fallopian tube was found to be enlarged,with widespread disseminated lesions extending from the pelvic cavity to the upper abdomen.Histopathological examination of the peritoneal tissue obtained by biopsy showed tumor cells with a high nuclear/cellular ratio and proliferation of papillary tubular to pedunculated solid nests.Immunohistochemical testing was positive for GATA-binding protein 3,thyroid transcription factor 1,cluster of differentiation 10,and paired box protein-8,and negative for estrogen receptor,Wilms’tumor 1,and wild-type p53,leading to the diagnosis of MLA.Subsequently,debulking surgery was performed,and no macroscopic residual tumors were identified.The pathological diagnosis was right tubal carcinoma,mesonephric adenocarcinoma(International Federation of Gynecology and Obstetrics stage IIIC),and pT3cNXM0.Adjuvant chemotherapy was administered postoperatively;however,recurrence was noted,and the patient died 1 year and 6 months after the initial treatment.CONCLUSION MLA is a very rare disease with poor prognosis.Further studies are necessary to identify effective treatment options.
基金supported by the postdoctoral fellowship program of CPSF(GZC20241270)the China Postdoctoral Science Foundation(2024M762496).
文摘Tumor cell-intrinsic programmed death-ligand 1(PD-L1)signals mediate tumor initiation,progression and metastasis,but their effects in ameloblastoma(AM)have not been reported.In this comprehensive study,we observed marked upregulation of PD-L1 in AM tissues and revealed the robust correlation between elevated PD-L1 expression and increased tumor growth and recurrence rates.Notably,we found that PD-L1 overexpression markedly increased self-renewal capacity and promoted tumorigenic processes and invasion in hTERT^(+)-AM cells,whereas genetic ablation of PD-L1 exerted opposing inhibitory effects.By performing highresolution single-cell profiling and thorough immunohistochemical analyses in AM patients,we delineated the intricate cellular landscape and elucidated the mechanisms underlying the aggressive phenotype and unfavorable prognosis of these tumors.Our findings revealed that hTERT^(+)-AM cells with upregulated PD-L1 expression exhibit increased proliferative potential and stem-like attributes and undergo partial epithelial-mesenchymal transition.This phenotypic shift is induced by the activation of the PI3KAKT-mTOR signaling axis;thus,this study revealed a crucial regulatory mechanism that fuels tumor growth and recurrence.Importantly,targeted inhibition of the PD-L1-PI3K-AKT-mTOR signaling axis significantly suppressed the growth of AM patientderived tumor organoids,highlighting the potential of PD-L1 blockade as a promising therapeutic approach for AM.
文摘在法医学检案中,经常要对尸体上的损伤进行检验以确定生前伤或死后伤,并要鉴定损伤时间.损伤超过8小时者一般用常规组织学方法可以解决,但损伤后经过时间较短,单用组织学方法不能解决,如利用酶活性反应方法和利用在组织内细胞内进行特异、灵敏、稳定的抗原抗体反应,可以较准确鉴定损伤时间.Perper J. A. Raek Allio、Tanaka、Fatteh等报导用组织化学方法鉴定损伤时间,祝家镇、刘世仓教授近年来也有报道,但用免疫组化学方法来鉴定损伤后早期时间,就作者所知,国内、外未见报道,而FN在创伤愈合过程中的作用国内外已有报道.
文摘The immunohistochemical localization of IAA and the comparison of their relative levels were carried out for the first time in the anthers of Nongken 58S and its wild type Nongken 58 (Oryza sativa subsp. japonica) after long_day and short_day treatments. The distribution of free_IAA in anthers and its dynamic variation could be reflected by this method. The results showed that the IAA level in the anthers of Nongken 58S after long_day treatment was much lower than that in short_day_treated Nongken 58S and those in wild type Nongken 58 in five stages from pistil and stamen primordia formation to late uninucleate stage. The possible reasons for IAA deficiency in Nongken 58S_LD anthers and its relationship with fertility alteration were also discussed.
文摘AIM: To improve the clinical diagnosis and recognition of hepatic epithelioid angiomyolipoma(HEAML).METHODS: Four cases of primary HEAML were confirmed based on the pathology archive system in our hospital from January 2009 to November 2015. The general state, clinical symptoms, imaging manifestations, histological results and immunohistochemistry of these patients were retrospectively reviewed and analyzed. Studies of HEAML published in the last 15 years were collected from Pub Med and MEDLINE to summarize the clinical symptoms, imaging characteristics, pathological features and management of HEAML.RESULTS: Four cases of primary HEAML were retrieved from our archives. These included three female patients and one male patient, with a mean age of 41.8 ± 11.5 years(ranging from 31 to 56 years). The meantumor size was 7.3 ± 5.5 cm(ranging from 3.0 to 15 cm). In the contrast-enhanced imaging, the tumor was obviously enhanced in the arterial phase, but enhanced continuously or exhibited a slow-density masse during the venous and delayed phases. Histologically, the tumors mainly consisted of epithelioid cells that comprised approximately 95% of the total neoplastic mass. Although no metastases occurred in our patients, pathological studies revealed necrosis, mitotic figures and liver invasion in two patients, which indicates aggressive behavior. Immunohistochemical staining revealed that human melanoma black 45(HMB-45) and Melan-A were positive in 4 cases. We only identified 81 cases with primary HEAML, including our present patients, from 26 articles available from Pub Med and MEDLINE. The majority of the papers were published as case reports. Only 5(5/75, 6%) cases were associated with tuberous sclerosis complex(TSC). More than half(35/66) were discovered incidentally upon physical examination. Approximately 65%(22/34) of the patients were misdiagnosed with HCC or other tumors before surgery. Approximately 10%(8/81) of the patients with HEAML had recurrence or metastasis after surgery, which was a very high and alarming rate.CONCLUSION: HEAML is a very rare primary hepatic tumor that is often misdiagnosed before surgery. Patients should be followed closely after surgery because of its malignant potential.
基金supported by the National Key R&D Program of China (No.2016YFC1303200)the National Natural Science Foundation of China (No. 81502060)Institutional Basic Research Funding (No.NCC2016YKY-06, JK2014B14)
文摘Background: Esophageal squamous cell carcinoma(ESCC) is an aggressive malignancy, with a high incidence and poor prognosis. In the past several decades, hundreds of proteins have been reported to be associated with the prognosis of ESCC, but none has been widely accepted to guide clinical care. This study aimed to identify proteins with great potential for predicting prognosis of ESCC.Methods: We conducted a systematic review on immunohistochemical(IHC) prognostic markers of ESCC according to the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA) Guidelines. Literature related to IHC prognostic markers of ESCC were searched from PubMed, Embase, Web of Science, and Cochrane Library until January 30 th, 2017. The risk of bias of these original studies was evaluated using the Quality in Prognosis Studies(QUIPS) tool.Results: We identified 11 emerging IHC markers with reproducible results, including eight markers [epidermal growth factor receptor(EGFR), Cyclin D1, vascular endothelial growth factor(VEGF), Survivin, Podoplanin, Fascin,phosphorylated mammalian target of rapamycin(p-mTOR), and pyruvate kinase M2(PKM2)] indicating unfavorable prognosis and 3 markers(P27, P16, and E-cadherin) indicating favorable prognosis of ESCC.Conclusion: Strong evidence supports that these 11 emerging IHC markers or their combinations may be useful in predicting prognosis and aiding personalized therapy decision-making for ESCC patients.
文摘AIM To further study the role of bcl 2 protein expression in gastric carcinogenesis and tumor progression. METHODS Using immunohistochemical staining, the bcl 2 protein expression in 50 cases of gastric carcinoma and its relation to clinical status and pathomorphological parameters were observed. RESULTS Forty one (82%) cases were positive for bcl 2 protein staining which was located in the cytoplasm and nuclear membrane of tumor cells. The rate of bcl 2 protein expression was not correlated with the patient, sex, tumor size, lymph node status or clinical stages ( P >0 05). It was strongly associated with intestinal type tumors and poorly differentiated tumors ( P <0 05 and P <0 01). CONCLUSION Aberrant bcl 2 protein expression appears to be specifically associated with development of intestinal type gastric carcinoma, bcl 2 protein expression might play an important role in the early development/promotion and phenotypic differentiation of gastric carcinomas, but not in tumor progression.
文摘AIM: To retrospectively evaluate the computed tomography (CT)/magnetic resonance imaging (MRI) imaging features of epithelioid angiomyolipoma of the liver (Epi-HAML), with pathology as a reference. METHODS: The CT/MRI findings (number, diameter, lobar location, and appearance of lesions) in a series of 10 patients with 12 pathologically proven epithelioid angiomyolipomas of the liver were retrospectively analyzed. The imaging features, including attenuation/ signal intensity characteristics, presence of fat, hypervascular, outer rim, and vessels within lesion, were evaluated and compared with that of non-Epi- HAML in 11 patients (13 lesions). The Fisher exact test was used to compare difference in probability of imaging features between the two types. RESULTS: For 21 patients, CT images of 15 patients and MR images of six patients were available. No patient underwent two examinations. For the 15 patients with a CT scan, all HAML lesions in the two groups (10 Epi-HAML and seven non-Epi-HAML) manifested as hypoattenuation. For the six patients with MRI, all lesions (two Epi-HAML and six non-Epi- HAML) were hypointense on TlWI (fat suppression) and hyperintense on T2WI. There were 10 non-Epi-HAML, but only two Epi-HAML lesions showed the presence of fat, which significantly different between the two types (P = 0.005). On the dynamic contrast enhancement (DCE) imaging, eight Epi-HAML, and 13 non-Epi lesions manifested as hypervascular. Punctate or curved vessels were displayed in 10 Epi-HAML as well as in nine non- Epi lesions and outer rim enhancement could be found with eight Epi-HAML as well as six non-Epi lesions. CONCLUSION: Little or no presence of adipose tissue was found to be an imaging feature of Epi- HAML, compared with the non-Epi type. In addition, hypervascularity with opacification of central punctiform or filiform vessels on DCE would be a characteristic enhancement pattern for Epi-HAML.
文摘BACKGROUND Intrahepatic sarcomatoid chonalgiocarcinoma(s-CCC) is an extremely rare disease, accounting for less than 1% of hepatobiliary system malignancies, and its pathophysiology is not well known. On the hypothesis that its clinical, serologic,or radiologic diagnosis are not fully understood and its prognosis is poor, we investigated the distinguishing features of s-CCC compared with those of intrahepatic bile duct adenocarcinoma [cholangiocellular carcinoma(CCC)] in patients from a single center.AIM To analyze the clinical, serologic, imaging, and histopathologic characteristics of intrahepatic s-CCC patients diagnosed in a single center.METHODS The clinical, serologic, imaging, and histopathologic features of 227 patients diagnosed with intrahepatic cholangiocarcinoma(IHCC) in a single medical center during the last 17 years were analyzed. The characteristics of 11 patients with s-CCC were compared with those of 216 patients with CCC.RESULTS The number of patients with s-CCC who presented fever and abdominal pain and past history of chronic viral hepatitis or liver cirrhosis(LC) was higher than that of patients with CCC. In imaging studies, patients with s-CCC showed relatively aggressive features. However, no clear distinction was observed between s-CCC and CCC based on other clinical, serologic or radiologic examination results. An accurate diagnosis could be made only via a histopathologic examination through immunohistochemical staining. The clinical course of s-CCC was generally aggressive, and patients had a relatively poor prognosis.CONCLUSION In patients with s-CCC, early diagnosis through biopsy and aggressive treatment,including surgical resection, are important.
基金Supported by Scientific Research Foundation of Shandong Province for Outstanding Young Scientist Award,No.2009GG20002037
文摘AIM:To investigate semaphorin 4D(Sema4D)and hypoxia-inducible factor-1α(HIF-1α)expression in colorectal carcinoma and evaluate their clinicopathological and prognostic significance.METHODS:Eighty-six curatively resected colorectal carcinoma patients at different stages of disease were randomly selected from the group of patients who underwent surgery,and none of them received preoperative radiochemotherapy.Normal proximal adjacent bowel tissue,which served as an internal control,was obtained from 52 randomly selected patients.Immunohistochemistry was performed to analyze the expression of Sema4D and the tumor angiogenesisrelated protein HIF-1αin normal colorectal tissues and colorectal carcinoma tissues.The relationships between the expression and clinical characters and prognosis were analyzed.RESULTS:HIF-1αand Sema4D were positively expressed in 58%and 60%of colorectal carcinoma tissues,respectively.Significantly lower expression levels were observed in normal mucosa(8%and 12%,respectively).HIF-1αand Sema4D expression was closely correlated with histological tumor type,tumornode-metastasis(TNM)stage,and lymphatic metastasis(P<0.05),but not with age or tumor size(P>0.05).HIF-1αand Sema4D protein expression was significantly correlated with prognosis of colorectal carcinoma,as determined by Spearman rank correlation analysis(r=0.567;P<0.01).Multivariate Cox analysis revealed that only Sema4D expression played a significant role in predicting patient prognosis(P<0.05).CONCLUSION:These findings suggest that HIF-1αand Sema4D expression correlates with histological tumor type,TNM stage,and lymphatic metastasis in colorectal carcinoma and that Sema4D is a prognostic indicator of colorectal carcinoma.
基金supported by Henan Province Higher Learning Institution Outstanding Scientific Research Talent Innovation Engineering Project (2007KYCX007)Henan Province Outstanding Youth Project (08100510015)
文摘Objective:To explore the mechanism of Buyang Huanwu Tang (补阳还五汤 Decoction Invigorating Yang for Recuperation) combined with bone marrow mesenchymal stem cells (MSCs) transplantation in protecting nerves of cerebral ischemic injury. Methods: Local cerebral ischemia-reperfusion rat model was established with modified Zea-Longa thread-occlusion method, and MSCs were injected into the caudal vein, and Buyang Huanwu Tang(补阳还五汤)was administrated. Vascular endothelial growth factor (VEGF) and Ki-67 expression in the ischemic side of the brain in the cerebral ischemic-reperfusion rat were detected with immuno-histochemical staining method. Results: VEGF and Ki-67 expressions were significantly up-regulated in the MSCs group and the combination group, with significant differences as compared with the model group and the sham operation group (P<0.05), and with the most strongest effect in the combination group. Conclusion: Buyang Huanwu Tang(补阳还五汤)combined with MSCs transplantation repairs the injured blood vessels and lesion tissues possibly by up-regulation of VEGF and Ki-67 expression.
文摘Hepatocellular carcinoma(HCC) accounts for over 90% of all primary liver cancers. With an ever increasing incidence trend year by year,it has become the third most common cause of death from cancer worldwide. Hepatic resection is generally considered to be one of the most effective therapies for HCC patients,however,there is a high risk of recurrence in postoperativeHCC. In clinical practice,there exists an urgent need for valid prognostic markers to identify patients with prognosis,hence the importance of studies on prognostic markers in improving the prediction of HCC prognosis. This review focuses on the most promising immunohistochemical prognostic markers in predicting the postoperative survival of HCC patients.
基金Supported by Hubei Province Natural Science Foundation,No.2000J054
文摘AIM:To clarify the clinicopathologic significance of COX-2 expression in human colorectal cancer.METHODS:A total of 128 surgically resected colorectal cancer specimens were immunohistochemically analyzed with the use of anti-COX-2,anti-VEGF and anti-MMP-2 antibodies.The relationship between the cyclooxygenase-2 expression in primary lesions of colorectal cancer and clinicopathoiogic parameters was evaluated by chi-square test.RESULTS:Among 128 cases of colorectal cancer,87(67.9%)were positive for cyclooxygenase-2.The expression of cyclooxygenase-2 was significantly correlated with the depth of invasion,stage of disease,and metastasis(lymph node and liver).Patients in T3-T4,stagesⅢ-Ⅳand with metastasis had much higher expression of cyclooxygenase-2 than ones in T1-T2,stagesⅠ-Ⅱand without metastasis(P<0.05).Among 45 cases of colorectal cancer with lymph node metastasis,the COX-2-positive rate was 86.7%(39/45)for primary lesions and diffuse cytoplasmic staining for COX-2 protein was detected in cancer cells in 100%of metastatic lesions of the lymph nodes.VEGF expression was detected in 49 tumors(38.3%),and VEGF expression was closely correlated with COX-2 expression.The positive expression rate of VEGF(81.6%)in the cyclooxygenase-2-positive group was higher than that in the cyclooxygenase-2-negative group(18.4%,P<0.05).MMP-2 expression was detected in 88 tumors(68.8%),and MMP-2 expression was closely correlated with COX-2 expression.The positive expression rate of MMP-2(79.6%)in the positive COX-2 group was higher than that in the negative COX-2 group(20.4%,P<0.05).CONCLUSION:Cyclooxygenase-2 may be associated with tumor progression by modulating the angiogenesis and cancer cell motility and invasive potential in colorectal cancer and it can be used as a possible biomarker.
基金supported by Zhejiang Provincial Administration of Traditional Chinese Medicine(20132a039)
文摘Objective:To investigate the expression and significance of MMP-3 in synovium of knee joint at different stage in osteoarthritis(OA)patients.Methods:Knee synovial tissue were collected in90 OA patients(the OA group).Patients in the OA group was divided into 3 subgroups:gradeⅠsubgroup(n=30),gradeⅡsubgroup(n=30),gradeⅢsubgroup(n=30).Thirty patients served as control group,lmmunohistochemical assay was used to detect the expression of MMP-3 protein in the knee synovial tissue.Results:MMP-3 protein was detected in all knee synovial tissue.The expression of MMP-3 protein in the OA group was significantly higher that in the normal synovium(P<0.05),and the MMP-3 protein was mainly located in the cytoplasm.There was significant difference in the expression of MMP-3 protein between the gradeⅢsubgroup and the gradeⅠ,gradeⅡsubgroups(all P<0.05).The expression of MMP-3 protein was positively related to the severity of OA(r=0.912,P<0.05).Conclusions:The expression of MMP-3 protein are closely related to pathogenic mechanism of OA.It may be an important indicator of early diagnosis and the activity of the disease of osteoarthritis.
文摘Cytomegalovirus(CMV) infection is common in humans.The virus then enters a "latency phase" and can reactivate to different stimuli such as immunosuppression.The clinical significance of CMV infection in inflammatory bowel disease is different in Crohn's disease(CD) and ulcerative colitis(UC).CMV does not interfere in the clinical course of CD.However,CMV reactivation is frequent in severe or steroid-resistant UC.It is not known whether the virus exacerbates the disease or simply appears as a bystander of a severe disease.Different methods are used to diagnose CMV colitis.Diagnosis is classically based on histopathological identification of viral-infected cells or CMV antigens in biopsied tissues using haematoxylin-eosin or immunohistochemistry,other tests on blood or tissue samples are currently being investigated.Polymerase chain reaction performed in colonic mucosa has a high sensitivity and a positive result could be associated with a worse prognosis disease;further studies are needed to determine the most appropriate strategy with positive CMV-DNA in colonic mucosa.Specific endoscopic features have not been described in active UC and CMV infection.CMV colitis is usually treated with ganciclovir for several weeks,there are different opinions about whether or not to stop immunosuppressive therapy.Other antiviral drugs may be used.Multicenter controlled studies would needed to determine which subgroup of UC patients would benefit from early antiviral treatment.
文摘AIM: To investigate the expression of Neurensin-2 (NRSN2) in hepatocellular carcinoma (HCC) and its prognostic values in predicting survival. METHODS: The expression and prognostic significance of NRSN2 in HCC was examined by performing immunohistochemical analysis using a total of 110 HCC clinical tissue samples, and Western blotting analysis to further confirm the result. RESULTS: Decreased NRSN2 expression was shown in 70.9% cases. Loss of NRSN2 expression in HCC was significantly related to tumor size (P = 0.006). Larger tumor size was related to negative expression of NRSN2. Patients showing negative NRSN2 expression had a significantly shorter overall survival than those with positive expression (P = 0.008). Multivariate Cox regression analysis indicated that NRSN2 expression level was an independent factor of survival (P = 0.013). Western blotting analysis further confirmed decreased expression of NRSN2 in tumor tissues compared with non-tumorous tissues. CONCLUSION: Our study indicated that NRSIV2 could be a tumor suppressor gene for HCC and a candidate biomarker for long-term survival in HCC.
基金Supported by the Natural Science Foundation of Yunnan Province, China, No. 2000C0058M, and Scientific Research Foundation of the Education Department of Yunnan Province, No. 0011010
文摘AIM: To study the expressions of p27^kip1 protein and p27mRNA, the hypermethylation of p27^kip1 and the relation between them in various stages of hepatocarcinogenesis. METHODS: p27 protein and p27mRNA were detected by immunohistochemical staining and in situ hybridization respectively in 68 cases of normal liver, liver cirrhosis, pericancerous cirrhosis and hepatocellular carcinoma (HCC). The hypermethylation of p27^kip1 was detected by methylation-specific PCR (MSP) in 44 cases of normal liver, liver cirrhosis, and HCC. RESULTS: The positive rate of p27 protein was 66.7% (4/6) in normal liver, 60.0% (6/10) in liver cirrhosis, 50.0% (12/24) in pericancerous cirrhosis and 21.4% (6/28) in HCC. There were no statistical differences in normal liver, liver cirrhosis and pericancerous cirrhosis, but the positive rate of p27 protein significantly decreased in HCC compared to that in the other groups (P = 0.006, %2 = 7.664). The positive rate of p27^kip1 mRNA was 83.3% (5/6) in normal liver, 70.0% (7/10) in liver cirrhosis, 75.0% (18/24) in pericancerous cirrhosis and 25.0% (7/28) in HCC. There were no statistical differences in normal liver, liver cirrhosis and pericancerous cirrhosis, but the positive rate of p27^kip1 mRNA also significantly decreased in HCC compared to that in the other groups (P = 0.000, %2 = 16.600). In addition, there was a significant correlation between the expression of p27 protein and p27mRNA in the integrated group of normal liver and liver cirrhosis. However, no significant correlation was found between pericancerous cirrhosis and HCC. Using MSP, we found that 1 HCC in 44 cases (including 6 cases of normal liver, 10 cases of liver cirrhosis and 28 cases of HCC) was methylated, whose p27 protein and p27mRNA were negative. CONCLUSION: The reduction or loss of p27 protein and p27mRNA are potentially involved in hepatocarcinogenesis. The hypermethylation of p27 might lead to the loss of p27mRNA transcription.
文摘Objective: To study the relationship between lymph node metastases in esophageal carcinoma and its prognosis. Methods: We obtained 1500 resected lymph nodes from the specimen of 86 patients with resected esophageal carcinoma and checked these lymph nodes by routine histopathology. Additiionally, frozen tissue sections of 540 lymph nodes classified as tumor-free by routine histopathology were screened for micrometastases by immunohistology with the monoclonal antibody Ber-EP4. Results: Forty-two patients (49%) had pN0 disease, and 61 patients (71%) had lymph node micrometastases detected by immunohistochemistry, skip metastases detected by routine histopathology were present in 26%(11/42) of pN0 and 41%(18/44) of pN1 patients. Skipping of micrometastases detected by immunohistochemistry was found in 71%(61/86). Twenty-six of 42 patients (62%) with tumor staged as pN0 and 35 of 44 patients (80%) with stage pN1 had nodal micrometastasis. The presence of micrometastases was associated with a significantly decreased relapse-free time and overall survival (P<0.0001 and P=0.004, respectively). Conclusion: Lymph node skip metastases are a frequent event in esophageal carcinoma. Extensive lymph node sampling, in conjunction with immunohistochemical detection, will lead to accurate staging and prognosis.