AIM: To further characterize the possible relationship between the molecular changes and prognosis of ESC and to elucidate the possible mechanisms involved.METHODS: 114 specimens of ESC were collected from Linzhou cit...AIM: To further characterize the possible relationship between the molecular changes and prognosis of ESC and to elucidate the possible mechanisms involved.METHODS: 114 specimens of ESC were collected from Linzhou city, and all patients were followed up for more than 5 years after resection. Histopathological analysis and immunohistochemical staining (ABC) were employed to detect the alteration of MUC1.RESULTS: The positive immunostaining rate for MUC1 was 79 % (90/114), and the high-expression rate was 63 %(72/114). The mean survival periods (months) of those with high- and low-expression rates of MUC1 were 41 (95 % CI:35, 47) and 52 (95 % CI: 45, 59), respectively. Patients in the low-expression group obviously survived longer than those in high-expression group, and the difference was significant (P＜0.05). The expression of MUC1 protein in the esophageal carcinoma specimens with metastasis was stronger than those without metastasis, the difference was also significant (P＜0.05). The stepwise multivariate analysis showed that 'differentiation', 'expression of MUC1' and 'TNM staging' were the most important factors affecting the prognosis of esophageal carcinoma patients (P＜0.05).CONCLUSION: A good correlation between the alteration of MUC1 and the regional lymph node metastasis was observed. Furthermore, high-expression of MUC1 was associated with poor prognosis for esophageal cancer patients. These results indicated that MUC1 is a promising biomarker for predicting lymph node metastasis and prognosis in esophageal cancer.展开更多
AIM: To characterize the alteration and significance of p53and PCNA in cancer and adjacent tissues of concurrent cancersfrom the esophagus and gastric cardia in the same patient.METHODS: P53 and PCNA protein accumulat...AIM: To characterize the alteration and significance of p53and PCNA in cancer and adjacent tissues of concurrent cancersfrom the esophagus and gastric cardia in the same patient.METHODS: P53 and PCNA protein accumulation in 25patients with concurrent cancers from the esophagus andgastric cardia (CC, concurrent carcinomas of esophagealsquamous cell carcinoma and gastric cardia adenocarcinoma)were detected by immunohistochemical method (ABC).RESULTS: In CC patients, both esophageal squamous cellcarcinoma (SCC) and gastric cardia adenocarcinoma (GCA)tissues showed different positive immunostaining extent ofp53 and PCNA protein (P＞0.05). The positive immunostainingrates for p53 and PCNA were 60 % (15/25) and 92 % (23/25), respectively in SCC; and 40 % (10/25) and 88 % (22/25), respectively in GCA. 'Diffuse' immunostaining patternwas frequently observed in both p53 and PCNA. Highcoincidence rates for p53 and PCNA positive staining wereobserved in SCC and GCA from the same patients, andaccounted for 56 % and 96 %. In SCC patients, with thelesions progressed from normal esophageal epithelium (NOR)to basal cell hyperplasia (BCH) to dysplasia (DYS) tocarcinomain situ (CIS) to SCC, the positive rates for p53were 27 %, 50 %, 50 %, 29 % and 72 %, and 55 %, 70 %,75 %, 71% and 93 % for PCNA, respectively. In GCA, withthe lesions progressed from normal gastric cardia epitheliumto DYS to CIS to GCA, the positive rates of p53 expressionwere 44 %, 27 %, 22 % and 36 % respectively, the differencewas not significant; the positive rates of PCNA proteinexpression were 67 %, 64 %, 67 % and 86 %, respectively.The x2 test, Fisher's Exact Test, Mantel-Haenszel x2 Testand Kappa Test were used for the statistics.CONCLUSION: The high coincident alterations for P53 andPCNA in SCC and GCA from the same patient indicate thepossibility of similar molecular basis, which providesimportant molecular basis and etiological clue for similargeographic distribution and risk factors in SCC and GCA.展开更多
AIM: To characterize the protein files in blood from same patients with esophageal squamous cell carcinoma (ESCC) before and after operation at Me high-incidence area for ESCC in Henan Province, China. METHODS: Two-di...AIM: To characterize the protein files in blood from same patients with esophageal squamous cell carcinoma (ESCC) before and after operation at Me high-incidence area for ESCC in Henan Province, China. METHODS: Two-dimensional electrophoresis, silver staining and ImageMaster 2-DE analysis software were applied to the determination of protein files in the blood obtained from normal controls and ESCC patients before and after operation. RESULTS: A total of 655, 662 and 677 protein spots were identified, respectively, from the normal controls and ESCC patients before and after operation. No significant difference in the number of protein spots was observed between Me normal group and ESCC patients. A total of seven protein spots were identified wi~ a dramatic difference among the samples before and after operation. Six protein spots were up-regulated and one protein spot was down-regulated in the group after operation compared with those in normal and before operation. Three protein spots were further characterized by matrix-assisted laser desorption/ionization time of flying mass spectrometry (MALDI-TOF-MS). The proteins from these three spots were identified as serum amyloid A (SAA), amyloid related serum protein and haptoglobin. CONCLUSION: Serum amyloid A, amyloid related serum protein and haptoglobin may be related with ESCC and/or surgery. The significance of ~ese proteins needs to be further characterized. The present study provides informative data for Me establishment of serum protein profiles related with ESCC.展开更多
Gastric cardia adenocarcinoma (GCA) is an under-studied subject. The pathogenesis, molecular changes in the early stage of carcinogenesis and related risk factors have not been well characterized. There is evidence, h...Gastric cardia adenocarcinoma (GCA) is an under-studied subject. The pathogenesis, molecular changes in the early stage of carcinogenesis and related risk factors have not been well characterized. There is evidence, however, that GCA differs from cancer of the rest of the stomach in terms of natural history and histopathogenesis. Adenocarcinomas of the lower esophagus, esophagogastric junction (EGJ)and gastric cardia have been given much attention because of their increasing incidences in the past decades, which is in striking contrast with the steady decrease in distal stomach adenocarcinoma. In China, epidemiologically, GCA shares very similar geographic distribution with esophageal squamous cell carcinoma (SCC), especially in Linzhou (formerly Linxian County), Henan Province, North China,the highest incidence area of esophageal SCC in the world.Historically, both GCA and SCC in these areas were referred to as esophageal cancer (EC) by the public because of the common syndrome of dysphagia. In Western countries,Barrett's esophagus is very common and has been considered as an important precancerous lesion of adenocarcinoma at EGJ. Because of the low incidence of Barrett's esophagus in China, it is unlikely to be an important factor in early stage of EGJ adenocarcinoma development.However, Z line up-growth into lower esophagus may be one of the characteristic changes in these areas in early stage of GCA development. Whether intestinal metaplasia (IM) is a premalignant lesion for GCA is still not clear. Higher frequency of IM observed at adjacent GCA tissues in Henan suggests the possibility of IM as a precancerous lesion for GCA in these areas. Molecular information on GCA,especially in early stage, is very limited. The accumulated data about the changes of tumor suppressor gene, such as p53 mutation, and ontogeny, such as C-erbB2, especially the similar alterations in GCA and SCC in the same patient,indicated that there might be some similar risk factors,such as nitrosamine, involved in both GCA and SCC in Henan population. The present observations also suggest that GCA should be considered as a distinct entity.展开更多
AIM: To characterize cytochrome P4501A1 (CYPIA1), glutathione S-transferases (GSTs) and microsomal epoxide hydrolase (mEH) polymorphisms in Chinese esophageal cancer patients. METHODS: Multiplex polymerase chain react...AIM: To characterize cytochrome P4501A1 (CYPIA1), glutathione S-transferases (GSTs) and microsomal epoxide hydrolase (mEH) polymorphisms in Chinese esophageal cancer patients. METHODS: Multiplex polymerase chain reaction (PCR) and PCR based restriction fragment length polymorphisms (PCRRFLP) were used to detect polymorphism changes of CYP,GSTs and mEH on esophageal cancerous and precancerous lesions as well as in case control group. All the examination samples were obtained from Linzhou (formerly Linxian), Henan Province, the highest incidence area for esophageal. RESULTS: The frequency of CYP1A1 3'' polymorphism in case control group (26/38, 68 %) was significantly higher than in esophageal squamous cell carcinoma^roup (ESCC) (29/62, 47 %) (P<0.05). A significant difference in the incidence of mEH slow allele variant was observed between case control group (15/38, 39 %) and esophageal dysplasiagroup (22/32, 69 %) or ESCC group (39/62, 63 %) (P<0.05). However, no significant difference was observed among different groups in the polymorphisms of CYPIA1 exon 7, GSTM1, GSTT1, GSTP1 and mEH fast allele. CONCLUSION: The present results suggest that CYPIA1 3'' polymorphism may be one of the promising protectivef actors and its wild gene type may be an indicator for higher susceptibility to esophageal cancer, mEH slow allele variant,associated with the progression of esophageal precancerous lesions, may conthbute to the high susceptibility to esophageal carcinoma.展开更多
AIM: Microsatellites are the repeated DNA sequences scattered widely within the genomes and closely linked with many important genes. This study was designed to characterize the changes of microsatellite DNA loss of h...AIM: Microsatellites are the repeated DNA sequences scattered widely within the genomes and closely linked with many important genes. This study was designed to characterize the changes of microsatellite DNA loss of heterozygosity (LOH) in esophageal carcinogenesis. METHODS: Allelic deletions in 32 cases of matched precancerous, cancerous and normal tissues were examined by syringe microdissection under an anatomic microscope and microsatellite polymorphism analysis using 15 polymorphic markers on chromosomes 3p, 5q, 6p, 9p, 13q,17p, 17q and 18q.RESULTS: Microsatellite DNA LOH was observed in precancerous and cancerous tissues, except D9S1752. The rate of LOH increased remarkably with the lesions progressed from basal cell hyperplasia (BCH) to squamous cell carcinoma (SCC) (P＜0.05). Three markers, D9S171, D13S260 and TP53, showed the highest incidence of LOH (＞60%). LOH loci were different in precancerous and cancerous tissues. LOH in D3S1234 and TP53 was the common event in different lesions from the same patients. CONCLUSION: Microsatellite DNA LOH occurs in early stage of human esophageal carcinogenesis, even in BCH. With the lesion progressed, gene instability increases, the accumulation of this change may be one of the important mechanisms driving precancerous lesions to cancer.展开更多
基金National Outstanding Young Scientist Award of China ,NO.30025016NCI CA65871(U.S.A.)
文摘AIM: To further characterize the possible relationship between the molecular changes and prognosis of ESC and to elucidate the possible mechanisms involved.METHODS: 114 specimens of ESC were collected from Linzhou city, and all patients were followed up for more than 5 years after resection. Histopathological analysis and immunohistochemical staining (ABC) were employed to detect the alteration of MUC1.RESULTS: The positive immunostaining rate for MUC1 was 79 % (90/114), and the high-expression rate was 63 %(72/114). The mean survival periods (months) of those with high- and low-expression rates of MUC1 were 41 (95 % CI:35, 47) and 52 (95 % CI: 45, 59), respectively. Patients in the low-expression group obviously survived longer than those in high-expression group, and the difference was significant (P＜0.05). The expression of MUC1 protein in the esophageal carcinoma specimens with metastasis was stronger than those without metastasis, the difference was also significant (P＜0.05). The stepwise multivariate analysis showed that 'differentiation', 'expression of MUC1' and 'TNM staging' were the most important factors affecting the prognosis of esophageal carcinoma patients (P＜0.05).CONCLUSION: A good correlation between the alteration of MUC1 and the regional lymph node metastasis was observed. Furthermore, high-expression of MUC1 was associated with poor prognosis for esophageal cancer patients. These results indicated that MUC1 is a promising biomarker for predicting lymph node metastasis and prognosis in esophageal cancer.
基金National Outstanding Young Scientist Award of China, No.30025016Foundation of Henan Education Committee
文摘AIM: To characterize the alteration and significance of p53and PCNA in cancer and adjacent tissues of concurrent cancersfrom the esophagus and gastric cardia in the same patient.METHODS: P53 and PCNA protein accumulation in 25patients with concurrent cancers from the esophagus andgastric cardia (CC, concurrent carcinomas of esophagealsquamous cell carcinoma and gastric cardia adenocarcinoma)were detected by immunohistochemical method (ABC).RESULTS: In CC patients, both esophageal squamous cellcarcinoma (SCC) and gastric cardia adenocarcinoma (GCA)tissues showed different positive immunostaining extent ofp53 and PCNA protein (P＞0.05). The positive immunostainingrates for p53 and PCNA were 60 % (15/25) and 92 % (23/25), respectively in SCC; and 40 % (10/25) and 88 % (22/25), respectively in GCA. 'Diffuse' immunostaining patternwas frequently observed in both p53 and PCNA. Highcoincidence rates for p53 and PCNA positive staining wereobserved in SCC and GCA from the same patients, andaccounted for 56 % and 96 %. In SCC patients, with thelesions progressed from normal esophageal epithelium (NOR)to basal cell hyperplasia (BCH) to dysplasia (DYS) tocarcinomain situ (CIS) to SCC, the positive rates for p53were 27 %, 50 %, 50 %, 29 % and 72 %, and 55 %, 70 %,75 %, 71% and 93 % for PCNA, respectively. In GCA, withthe lesions progressed from normal gastric cardia epitheliumto DYS to CIS to GCA, the positive rates of p53 expressionwere 44 %, 27 %, 22 % and 36 % respectively, the differencewas not significant; the positive rates of PCNA proteinexpression were 67 %, 64 %, 67 % and 86 %, respectively.The x2 test, Fisher's Exact Test, Mantel-Haenszel x2 Testand Kappa Test were used for the statistics.CONCLUSION: The high coincident alterations for P53 andPCNA in SCC and GCA from the same patient indicate thepossibility of similar molecular basis, which providesimportant molecular basis and etiological clue for similargeographic distribution and risk factors in SCC and GCA.
基金Supported by National Science Fund for Outstanding Young Scholars of China,No.30025016State Basic Research Development Program of China,No.G 1998051206Foundation of Henan Education Committee,No.1999125 and the US NIH Grant,No.CA65871
文摘AIM: To characterize the protein files in blood from same patients with esophageal squamous cell carcinoma (ESCC) before and after operation at Me high-incidence area for ESCC in Henan Province, China. METHODS: Two-dimensional electrophoresis, silver staining and ImageMaster 2-DE analysis software were applied to the determination of protein files in the blood obtained from normal controls and ESCC patients before and after operation. RESULTS: A total of 655, 662 and 677 protein spots were identified, respectively, from the normal controls and ESCC patients before and after operation. No significant difference in the number of protein spots was observed between Me normal group and ESCC patients. A total of seven protein spots were identified wi~ a dramatic difference among the samples before and after operation. Six protein spots were up-regulated and one protein spot was down-regulated in the group after operation compared with those in normal and before operation. Three protein spots were further characterized by matrix-assisted laser desorption/ionization time of flying mass spectrometry (MALDI-TOF-MS). The proteins from these three spots were identified as serum amyloid A (SAA), amyloid related serum protein and haptoglobin. CONCLUSION: Serum amyloid A, amyloid related serum protein and haptoglobin may be related with ESCC and/or surgery. The significance of ~ese proteins needs to be further characterized. The present study provides informative data for Me establishment of serum protein profiles related with ESCC.
基金National Distinguished Young Scientist Foundation of China,No.30025016Foundation of Henan Education Committee.No.1999125
文摘Gastric cardia adenocarcinoma (GCA) is an under-studied subject. The pathogenesis, molecular changes in the early stage of carcinogenesis and related risk factors have not been well characterized. There is evidence, however, that GCA differs from cancer of the rest of the stomach in terms of natural history and histopathogenesis. Adenocarcinomas of the lower esophagus, esophagogastric junction (EGJ)and gastric cardia have been given much attention because of their increasing incidences in the past decades, which is in striking contrast with the steady decrease in distal stomach adenocarcinoma. In China, epidemiologically, GCA shares very similar geographic distribution with esophageal squamous cell carcinoma (SCC), especially in Linzhou (formerly Linxian County), Henan Province, North China,the highest incidence area of esophageal SCC in the world.Historically, both GCA and SCC in these areas were referred to as esophageal cancer (EC) by the public because of the common syndrome of dysphagia. In Western countries,Barrett's esophagus is very common and has been considered as an important precancerous lesion of adenocarcinoma at EGJ. Because of the low incidence of Barrett's esophagus in China, it is unlikely to be an important factor in early stage of EGJ adenocarcinoma development.However, Z line up-growth into lower esophagus may be one of the characteristic changes in these areas in early stage of GCA development. Whether intestinal metaplasia (IM) is a premalignant lesion for GCA is still not clear. Higher frequency of IM observed at adjacent GCA tissues in Henan suggests the possibility of IM as a precancerous lesion for GCA in these areas. Molecular information on GCA,especially in early stage, is very limited. The accumulated data about the changes of tumor suppressor gene, such as p53 mutation, and ontogeny, such as C-erbB2, especially the similar alterations in GCA and SCC in the same patient,indicated that there might be some similar risk factors,such as nitrosamine, involved in both GCA and SCC in Henan population. The present observations also suggest that GCA should be considered as a distinct entity.
基金National Outstanding Young Scientist Award of China 30025016(China)State Key Project for Basic Research G 1998051206(China)+1 种基金Foundation of Henan Education Committee 1999125the U.S.NIH Grant CA65871
文摘AIM: To characterize cytochrome P4501A1 (CYPIA1), glutathione S-transferases (GSTs) and microsomal epoxide hydrolase (mEH) polymorphisms in Chinese esophageal cancer patients. METHODS: Multiplex polymerase chain reaction (PCR) and PCR based restriction fragment length polymorphisms (PCRRFLP) were used to detect polymorphism changes of CYP,GSTs and mEH on esophageal cancerous and precancerous lesions as well as in case control group. All the examination samples were obtained from Linzhou (formerly Linxian), Henan Province, the highest incidence area for esophageal. RESULTS: The frequency of CYP1A1 3'' polymorphism in case control group (26/38, 68 %) was significantly higher than in esophageal squamous cell carcinoma^roup (ESCC) (29/62, 47 %) (P<0.05). A significant difference in the incidence of mEH slow allele variant was observed between case control group (15/38, 39 %) and esophageal dysplasiagroup (22/32, 69 %) or ESCC group (39/62, 63 %) (P<0.05). However, no significant difference was observed among different groups in the polymorphisms of CYPIA1 exon 7, GSTM1, GSTT1, GSTP1 and mEH fast allele. CONCLUSION: The present results suggest that CYPIA1 3'' polymorphism may be one of the promising protectivef actors and its wild gene type may be an indicator for higher susceptibility to esophageal cancer, mEH slow allele variant,associated with the progression of esophageal precancerous lesions, may conthbute to the high susceptibility to esophageal carcinoma.
基金Supported by National Outstanding Young Scientist Foundation of China, No. 30025016 State Basic Research Development Program of China, No. G1998051206 Foundation of Henan Education Committee, No. 1999125 and the US NIH Grant, No. CA65871
文摘AIM: Microsatellites are the repeated DNA sequences scattered widely within the genomes and closely linked with many important genes. This study was designed to characterize the changes of microsatellite DNA loss of heterozygosity (LOH) in esophageal carcinogenesis. METHODS: Allelic deletions in 32 cases of matched precancerous, cancerous and normal tissues were examined by syringe microdissection under an anatomic microscope and microsatellite polymorphism analysis using 15 polymorphic markers on chromosomes 3p, 5q, 6p, 9p, 13q,17p, 17q and 18q.RESULTS: Microsatellite DNA LOH was observed in precancerous and cancerous tissues, except D9S1752. The rate of LOH increased remarkably with the lesions progressed from basal cell hyperplasia (BCH) to squamous cell carcinoma (SCC) (P＜0.05). Three markers, D9S171, D13S260 and TP53, showed the highest incidence of LOH (＞60%). LOH loci were different in precancerous and cancerous tissues. LOH in D3S1234 and TP53 was the common event in different lesions from the same patients. CONCLUSION: Microsatellite DNA LOH occurs in early stage of human esophageal carcinogenesis, even in BCH. With the lesion progressed, gene instability increases, the accumulation of this change may be one of the important mechanisms driving precancerous lesions to cancer.
