AIM To determine the expression and clinicalsignificance of chromogranin A and cathepsin Din hepatocellular carcinoma(HCC).METHODS Double immunofluorescence stain-ing techniques combined with laser confocalscanning mi...AIM To determine the expression and clinicalsignificance of chromogranin A and cathepsin Din hepatocellular carcinoma(HCC).METHODS Double immunofluorescence stain-ing techniques combined with laser confocalscanning microscopy(LSCM)was used toinvestigate chromogranin A and cathepsin Dexpressions in 85 HCC patients.RESULTS Cathepsin D was expressed in :3normal liver tissues,while in HCC the stainingshowed regional variation and the fraction ofstrongly stained cells increased as the tumorsbecame less differentiated and usually clinicallymore malignant.Cells which showed strongpositivity for cathepsin D were present in 71/85(83.5%)cases.Strong expression of cathepsinD in cancer cells was related tohistopathological features.They were morecommon in grade 3-4(26/28,92.9%)and grade2(46/53,86.8%)tumors than in grade 1 tumors(1/4,25.0%)(P【0.01).No significantcorrelation was found between age andcathepsin D expression.In patients with positivecathepsin D reaction,the mean age was 52.1±2.8 years(range 32-68 years)and in the groupwith negative reaction,the mean age was 51.3±4.5 years(range 28-71 years).No obvious relationship was observed between CgAexpression in cancer cells and thehistopathological features.The CgA positiverate was 75.0%(3/4)in grade 1,71.7%(38/53)in grade 2,and 71.4%(20/28)in grade 3-4(P】0.05)tumors.The coexpression of CgA andcathepsin D was found by double labeledimmunofluorescence staining techniques.Theprocessing of cathepsin D was disturbed in HCCcells and accumulated in the cells.Cathepsin Dhad proteolytic activity and autocrine mitogeniceffect,suggesting their functions in invasion.These findings demonstrated that the expressionof cathepsin D in HCC had prognostic value.CONCLUSION Chromogranin A and cathepsin Dare expressed in a high proportion of HCC andthe existence of cathepsin D in HCC might berelated to processing of CgA.This is clearly asubject for further studies because of itspotential clinical applications.展开更多
OBJECTIVE:To explore the mechanism by which Qinghua decoction(清化饮)regulates neuroendocrine inflammation in chronic nonbacterial prostatitis(CNP)model rats and provide an experimental basis for clinical treatment.ME...OBJECTIVE:To explore the mechanism by which Qinghua decoction(清化饮)regulates neuroendocrine inflammation in chronic nonbacterial prostatitis(CNP)model rats and provide an experimental basis for clinical treatment.METHODS:The rats were randomly divided into six groups:normal control,model,Qianlie Tongyu capsule,low-dose Qinghua decoction,medium-dose Qinghua decoction,and high-dose Qinghua decoction group with six rats in each group.Rats in each group were sacrificed on the 29th day of treatment,and blood and prostate tissues were collected.Serum levels of tumor necrosis factor-alpha and interleukins 1-beta,6,8,and 10(TNF-αand IL-1β,-6,-8,and-10,respectively)were measured using enzyme-linked immunosorbent assay.The pathological changes in the rat prostate tissue in each group were observed under a light microscope.The expression levels of chromogranin A(CgA),nerve growth factor(NGF),and tyrosine kinase A(TrkA)were detected using reverse transcription quantitative polymerase chain reaction.Western blotting was used to detect protein expression of CgA,NGF,and TrkA.RESULTS:In the model group,the prostate capsule membrane and stroma were significantly dilated with more inflammatory cells infiltrating the stroma and perivessels.TNF-α,IL-1β,-6,and-8,CgA,NGF,and TrkA levels increased,whereas the content of IL-10 decreased,which was statistically significant compared to that in the normal control group(P<0.05).Prostate tissue cells in the high-dose group were neatly arranged with no obvious inflammatory cell infiltration.When compared with the model group,the high-dose Qinghua decoction group showed a significant improvement in these indices(P<0.05).CONCLUSION:Qinghua decoction led to inhibition of pathological changes in the prostate tissue of rats with CNP,regulation of inflammatory cytokine expression,and inhibition in the expression of CgA,NGF,and TrkA.This mechanism may be primarily related to regulation of the CgA/NGF/TrkA signaling pathway mediated by various inflammatory factors.展开更多
We aimed to investigate the prognostic value of chromogranin A （CgA） in castration-resistant prostate cancer （CRPC）. We conducted a systematic literature search of PubMed, Web of Science, and EMBASE for citations ...We aimed to investigate the prognostic value of chromogranin A （CgA） in castration-resistant prostate cancer （CRPC）. We conducted a systematic literature search of PubMed, Web of Science, and EMBASE for citations published prior to September 2017 that described CgA and CRPC and performed a standard meta-analysis on survival outcomes. Our meta-analysis included eight eligible studies with 686 patients. The results were as follows： progression-free survival （PFS） was associated with CgA level （hazard ratio [HR] = 2.47, 95% confidence interval [CI]： 1.47-4.14, P = 0.0006）; PFS was relative to CgA change （HR = 9.22, 95% Ch 3.03-28.05, P〈 0.0001）; and overall survival （OS） was relative to CgA level （HR = 1.47, 95% Ch 1.15-1.87, P= 0.002）. When we divided the patients into two groups according to therapy status, the result for OS relative to CgA level was an HR of 1.26 （95% CI： 1.09-1.45, P = 0.001） in the first-line hormonal therapy group, and an HR of 2.33 （95% Ch 1.40-3.89, P = 0.001） in the second-line hormonal therapy or chemotherapy group. This meta-analysis indicated that a high CgA level had a negative influence on OS and PFS in CRPC patients. In addition, CRPC patients with a rising CgA had a shorter PFS. Further studies are needed to verify the prognostic value of CgA in CRPC.展开更多
Burning mouth syndrome (BMS) is a poorly understood oral pain disorder characterized by a painful burning sensation in the oral cavity without any mucosal abnormalities. In this study, we evaluated the salivary cortis...Burning mouth syndrome (BMS) is a poorly understood oral pain disorder characterized by a painful burning sensation in the oral cavity without any mucosal abnormalities. In this study, we evaluated the salivary cortisol and chromogranin A (CgA) levels of patients with BMS in comparison with age-matched controls. Subjects (n = 114) included 81 BMS patients and 33 controls. Patients with BMS were further classified into a subgroup of subjects who occasionally feel a burning sensation (BMS 1), and a subgroup of subjects who always feel a burning sensation (BMS 2). Salivary cortisol and CgA levels were measured using ELISA kits. All individuals with BMS had significantly higher cortisol and CgA levels than the controls did. Furthermore, when comparing the controls with each BMS subgroup, salivary levels of cortisol were significantly higher in both subgroups than controls. In contrast, the level of CgA was significantly higher in the BMS 2 subgroup only. Multiple regression analysis revealed a significant independent association between salivary levels of cortisol and BMS even after adjustment for gender, antidepressant or antianxiety drug use and hypertension (drug-treated). The study revealed that a significant association was observed between salivary cortisol levels and BMS.展开更多
Chromogranin A, due to its primary expression throughout the neuroendocrine system, is a widely accepted biomarker for the assessment of neuro-endocrine tumors. It has been traditionally used in the management of pati...Chromogranin A, due to its primary expression throughout the neuroendocrine system, is a widely accepted biomarker for the assessment of neuro-endocrine tumors. It has been traditionally used in the management of patients with tumors of gastro-enteropancreatic origin. Lately, it has also been implicated in various conditions and diseases, both benign and malignant. However, the paucity of data of adequate strength, as well as its relation with common physiologic conditions and its interaction with commonly prescribed medications, limit its clinical use in only a narrow spectrum. Herein, we present a thorough review to the most frequent conditions where its levels are affected, focusing specifically on its potential use as a prognostic and predictive biomarker in oncology.展开更多
Aim:Prostate cancer(PCa)is the second most prevalent male cancer worldwide and designated the sixth most frequent male cancer in Arab countries.Although prostate specific antigen(PSA)has become the best and most valua...Aim:Prostate cancer(PCa)is the second most prevalent male cancer worldwide and designated the sixth most frequent male cancer in Arab countries.Although prostate specific antigen(PSA)has become the best and most valuable biomarker for screening of PCa,elevated levels of PSA can reflect the presence of malignant cells but can overlap with benign prostatic diseases.There is a necessity to develop and improve current tools for early detection and diagnosis of PCa.This study was done to evaluate the validation of serum insulin-like growth factor-1(IGF-1),IGF binding protein-3(IGFBP-3),chromogranin A(CgA)and combination with PSA in treatment of benign prostatic hyperplasia(BPH)and PCa patients.Methods:The study included 72 patients with PCa,70 BPH patients and 56 healthy male subjects of matched age.Full history and clinical data were recorded for all subjects.Results:Serum PSA attained sensitivity of 84%at 82%specificity with an accuracy of 83%,although IGF-1,IGFBP-3 and CgA did not recognize PCa patients.Conclusion:Combinations of IGF-1 and IGFBP-3 biomarkers with PSA were effectively differentiated between PCa and control groups as well as improving the overall value of sensitivity,specificity and diagnostic accuracy of PCa to 85%and 86%for IGF-1/PSA and IGFP-3/PSA respectively.展开更多
Chromogranin A (CgA) is a kind of acidic protein originally isolated from the chromaffin cells of the ox adrenal gland medulla. It was found that the CgA was also widely distributed in the neuroendocrine cells besides...Chromogranin A (CgA) is a kind of acidic protein originally isolated from the chromaffin cells of the ox adrenal gland medulla. It was found that the CgA was also widely distributed in the neuroendocrine cells besides the adrenal medulla. The physiological function of the CgA is not yet elucidated, but it was presumed to be involved in organizing the granule matrix and regulating the processing of the prohormones. Besides, CgA is also the precursor of some peptide hormones such展开更多
目的:胃肝样腺癌(hepatoid adenocarcinoma of the stomach,HAS)是一种罕见的胃癌亚型,其形态学类似肝细胞癌。部分病例可伴有神经内分泌标志物的免疫组织化学表达,其中少数病例表达显著。本研究旨在通过回顾性分析具有显著神经内分泌...目的:胃肝样腺癌(hepatoid adenocarcinoma of the stomach,HAS)是一种罕见的胃癌亚型,其形态学类似肝细胞癌。部分病例可伴有神经内分泌标志物的免疫组织化学表达,其中少数病例表达显著。本研究旨在通过回顾性分析具有显著神经内分泌免疫组织化学特征HAS患者的临床资料,为提高此类患者的临床诊断水平提供帮助。方法:纳入苏州大学附属第一医院收治的具有显著神经内分泌免疫组织化学特征的HAS患者。患者均具有典型的HAS病理特征,且至少表达神经内分泌免疫组织化学指标突触素(synaptophysin,Syn)和嗜铬粒蛋白A(chromogranin A,CgA)中的1种。对患者的一般临床资料,以及肿瘤组织的大体形态、HE染色结果、免疫组织化学染色结果进行回顾性分析。结果:纳入患者13例,其中男11例,女2例,年龄55~79(67.9±8.8)岁。患者血清甲胎蛋白(alpha fetoprotein,AFP)水平为14.73~902.54μg/L。肿瘤部位:贲门5例,胃底2例,胃角2例,胃窦4例。肿瘤最大径2.5~10.0 cm,切面呈灰白色。1例为隆起型(Borrman I型),12例为溃疡型(Borrman Ⅲ型)。肿瘤细胞部分呈弥漫、片状分布,部分呈结节状分布,间质血窦丰富。细胞呈多边形,体积中等或偏大,细胞质呈嗜酸性、嗜碱性或透明,核分裂象易见,部分管腔内或细胞内可见嗜伊红物质。在13例HAS患者中,婆罗双树样基因4(spalt-like transcription factor 4,SALL4)阳性11例,AFP阳性6例,磷脂酰肌醇蛋白聚糖3(glypican-3,GPC3)阳性4例,Syn阳性13例,CgA阳性12例,CD56阳性7例,胰岛素瘤相关蛋白1(insulinoma-associated protein 1,INSM1)阳性7例,细胞角蛋白(cytokeratin,CK)7阳性4例。Ki-67增殖指数为60%~90%。人表皮生长因子受体-2(human epidermal growth factor receptor 2,HER-2)表达为0的有9例,1+的有4例。1例患者接受术前新辅助化疗和术后化疗,8例只接受了术后化疗,4例未进行化疗。随访时间3~57个月,7例患者因肿瘤死亡,6例存活。结论:HAS可表现为显著的神经内分泌免疫组织化学特征,预后较差。明确HAS可具有显著神经内分泌免疫组织化学特征,有助于加深对此类肿瘤的认识,减少误诊、漏诊的发生。展开更多
BACKGROUND Pancreatic neuroendocrine microtumors(PNEMTs)are small(<5 mm),nonfunctioning,well-differentiated neuroendocrine neoplasms.Although they are rare,they are not invariably benign.PNEMTs are typically discov...BACKGROUND Pancreatic neuroendocrine microtumors(PNEMTs)are small(<5 mm),nonfunctioning,well-differentiated neuroendocrine neoplasms.Although they are rare,they are not invariably benign.PNEMTs are typically discovered incidentally during autopsy.However,data regarding the occurrence of PNEMTs in the elderly population,particularly those identified incidentally in cadaveric studies,remain limited.AIM To investigate the prevalence and histopathological characteristics of PNEMTs in elderly individuals by analyzing cadaveric pancreatic tissues.METHODS We conducted a retrospective analysis of 85 pancreatic specimens(age range:58-109 years)obtained from cadavers for anatomical education and research at the Department of Life Dentistry,Nippon Dental University.Paraffin sections of the pancreatic head,body,and tail were prepared for histological and immunohistochemical analysis.RESULTS Five cases with PNEMTs(5/85,5.9%;male,n=33;female,n=52;mean age:85.8±12.1 years)were identified.The tumors were solitary,well circumscribed,and located within the pancreatic parenchyma(body:n=4;tail:n=1),and all were<5 mm(range:0.54-2.20 mm)in size.All tumors showed strong chromogranin A and synaptophysin positivity,and were predominantly glucagon(GLU)-positive.Ki-67 immunostaining indicated minimal proliferative activity;therefore,these tumors were considered non-functioning,GLU-producing,well-differentiated grade 1 PNEMTs.CONCLUSION Small,predominantly low-grade,GLU-secreting PNEMTs were present in 5.9%of elderly individuals,highlighting the prevalence of subclinical PNEMTs and the need for careful follow-up.展开更多
基金the Foundation of Chinese PLA 117 Hospital,No.98009
文摘AIM To determine the expression and clinicalsignificance of chromogranin A and cathepsin Din hepatocellular carcinoma(HCC).METHODS Double immunofluorescence stain-ing techniques combined with laser confocalscanning microscopy(LSCM)was used toinvestigate chromogranin A and cathepsin Dexpressions in 85 HCC patients.RESULTS Cathepsin D was expressed in :3normal liver tissues,while in HCC the stainingshowed regional variation and the fraction ofstrongly stained cells increased as the tumorsbecame less differentiated and usually clinicallymore malignant.Cells which showed strongpositivity for cathepsin D were present in 71/85(83.5%)cases.Strong expression of cathepsinD in cancer cells was related tohistopathological features.They were morecommon in grade 3-4(26/28,92.9%)and grade2(46/53,86.8%)tumors than in grade 1 tumors(1/4,25.0%)(P【0.01).No significantcorrelation was found between age andcathepsin D expression.In patients with positivecathepsin D reaction,the mean age was 52.1±2.8 years(range 32-68 years)and in the groupwith negative reaction,the mean age was 51.3±4.5 years(range 28-71 years).No obvious relationship was observed between CgAexpression in cancer cells and thehistopathological features.The CgA positiverate was 75.0%(3/4)in grade 1,71.7%(38/53)in grade 2,and 71.4%(20/28)in grade 3-4(P】0.05)tumors.The coexpression of CgA andcathepsin D was found by double labeledimmunofluorescence staining techniques.Theprocessing of cathepsin D was disturbed in HCCcells and accumulated in the cells.Cathepsin Dhad proteolytic activity and autocrine mitogeniceffect,suggesting their functions in invasion.These findings demonstrated that the expressionof cathepsin D in HCC had prognostic value.CONCLUSION Chromogranin A and cathepsin Dare expressed in a high proportion of HCC andthe existence of cathepsin D in HCC might berelated to processing of CgA.This is clearly asubject for further studies because of itspotential clinical applications.
基金Hebei Administration of Traditional Chinese Medicine Project:Study on the Neuroendocrine Mechanism of Chronic Prostatitis Rats Regulated by the Method of Clearing heat and Dampness,Activating Blood and Removing Stasis(No.2019087)Hebei Provincial Department of Education for Postgraduate Innovation Ability Training Project:the Mechanism of Improving Pulmonary Function of COPD Rats with Lung Qi Deficiency by Regulating Intestinal Bacteria with Peitu Shengjin Formula(No.CXZZBS2020151)Provincial Universities Basic Research Funds Special Project:Study on the Mechanism of Shenling Baizhu Powder Based on Lung Intestine Axis to Interfere with the Deficiency of Lung and Spleen in Experimental COPD(YJZ2019010)。
文摘OBJECTIVE:To explore the mechanism by which Qinghua decoction(清化饮)regulates neuroendocrine inflammation in chronic nonbacterial prostatitis(CNP)model rats and provide an experimental basis for clinical treatment.METHODS:The rats were randomly divided into six groups:normal control,model,Qianlie Tongyu capsule,low-dose Qinghua decoction,medium-dose Qinghua decoction,and high-dose Qinghua decoction group with six rats in each group.Rats in each group were sacrificed on the 29th day of treatment,and blood and prostate tissues were collected.Serum levels of tumor necrosis factor-alpha and interleukins 1-beta,6,8,and 10(TNF-αand IL-1β,-6,-8,and-10,respectively)were measured using enzyme-linked immunosorbent assay.The pathological changes in the rat prostate tissue in each group were observed under a light microscope.The expression levels of chromogranin A(CgA),nerve growth factor(NGF),and tyrosine kinase A(TrkA)were detected using reverse transcription quantitative polymerase chain reaction.Western blotting was used to detect protein expression of CgA,NGF,and TrkA.RESULTS:In the model group,the prostate capsule membrane and stroma were significantly dilated with more inflammatory cells infiltrating the stroma and perivessels.TNF-α,IL-1β,-6,and-8,CgA,NGF,and TrkA levels increased,whereas the content of IL-10 decreased,which was statistically significant compared to that in the normal control group(P<0.05).Prostate tissue cells in the high-dose group were neatly arranged with no obvious inflammatory cell infiltration.When compared with the model group,the high-dose Qinghua decoction group showed a significant improvement in these indices(P<0.05).CONCLUSION:Qinghua decoction led to inhibition of pathological changes in the prostate tissue of rats with CNP,regulation of inflammatory cytokine expression,and inhibition in the expression of CgA,NGF,and TrkA.This mechanism may be primarily related to regulation of the CgA/NGF/TrkA signaling pathway mediated by various inflammatory factors.
文摘We aimed to investigate the prognostic value of chromogranin A （CgA） in castration-resistant prostate cancer （CRPC）. We conducted a systematic literature search of PubMed, Web of Science, and EMBASE for citations published prior to September 2017 that described CgA and CRPC and performed a standard meta-analysis on survival outcomes. Our meta-analysis included eight eligible studies with 686 patients. The results were as follows： progression-free survival （PFS） was associated with CgA level （hazard ratio [HR] = 2.47, 95% confidence interval [CI]： 1.47-4.14, P = 0.0006）; PFS was relative to CgA change （HR = 9.22, 95% Ch 3.03-28.05, P〈 0.0001）; and overall survival （OS） was relative to CgA level （HR = 1.47, 95% Ch 1.15-1.87, P= 0.002）. When we divided the patients into two groups according to therapy status, the result for OS relative to CgA level was an HR of 1.26 （95% CI： 1.09-1.45, P = 0.001） in the first-line hormonal therapy group, and an HR of 2.33 （95% Ch 1.40-3.89, P = 0.001） in the second-line hormonal therapy or chemotherapy group. This meta-analysis indicated that a high CgA level had a negative influence on OS and PFS in CRPC patients. In addition, CRPC patients with a rising CgA had a shorter PFS. Further studies are needed to verify the prognostic value of CgA in CRPC.
文摘Burning mouth syndrome (BMS) is a poorly understood oral pain disorder characterized by a painful burning sensation in the oral cavity without any mucosal abnormalities. In this study, we evaluated the salivary cortisol and chromogranin A (CgA) levels of patients with BMS in comparison with age-matched controls. Subjects (n = 114) included 81 BMS patients and 33 controls. Patients with BMS were further classified into a subgroup of subjects who occasionally feel a burning sensation (BMS 1), and a subgroup of subjects who always feel a burning sensation (BMS 2). Salivary cortisol and CgA levels were measured using ELISA kits. All individuals with BMS had significantly higher cortisol and CgA levels than the controls did. Furthermore, when comparing the controls with each BMS subgroup, salivary levels of cortisol were significantly higher in both subgroups than controls. In contrast, the level of CgA was significantly higher in the BMS 2 subgroup only. Multiple regression analysis revealed a significant independent association between salivary levels of cortisol and BMS even after adjustment for gender, antidepressant or antianxiety drug use and hypertension (drug-treated). The study revealed that a significant association was observed between salivary cortisol levels and BMS.
文摘Chromogranin A, due to its primary expression throughout the neuroendocrine system, is a widely accepted biomarker for the assessment of neuro-endocrine tumors. It has been traditionally used in the management of patients with tumors of gastro-enteropancreatic origin. Lately, it has also been implicated in various conditions and diseases, both benign and malignant. However, the paucity of data of adequate strength, as well as its relation with common physiologic conditions and its interaction with commonly prescribed medications, limit its clinical use in only a narrow spectrum. Herein, we present a thorough review to the most frequent conditions where its levels are affected, focusing specifically on its potential use as a prognostic and predictive biomarker in oncology.
文摘Aim:Prostate cancer(PCa)is the second most prevalent male cancer worldwide and designated the sixth most frequent male cancer in Arab countries.Although prostate specific antigen(PSA)has become the best and most valuable biomarker for screening of PCa,elevated levels of PSA can reflect the presence of malignant cells but can overlap with benign prostatic diseases.There is a necessity to develop and improve current tools for early detection and diagnosis of PCa.This study was done to evaluate the validation of serum insulin-like growth factor-1(IGF-1),IGF binding protein-3(IGFBP-3),chromogranin A(CgA)and combination with PSA in treatment of benign prostatic hyperplasia(BPH)and PCa patients.Methods:The study included 72 patients with PCa,70 BPH patients and 56 healthy male subjects of matched age.Full history and clinical data were recorded for all subjects.Results:Serum PSA attained sensitivity of 84%at 82%specificity with an accuracy of 83%,although IGF-1,IGFBP-3 and CgA did not recognize PCa patients.Conclusion:Combinations of IGF-1 and IGFBP-3 biomarkers with PSA were effectively differentiated between PCa and control groups as well as improving the overall value of sensitivity,specificity and diagnostic accuracy of PCa to 85%and 86%for IGF-1/PSA and IGFP-3/PSA respectively.
文摘Chromogranin A (CgA) is a kind of acidic protein originally isolated from the chromaffin cells of the ox adrenal gland medulla. It was found that the CgA was also widely distributed in the neuroendocrine cells besides the adrenal medulla. The physiological function of the CgA is not yet elucidated, but it was presumed to be involved in organizing the granule matrix and regulating the processing of the prohormones. Besides, CgA is also the precursor of some peptide hormones such
基金Supported by Grant-in-Aid for Scientific Research from the Ministry of Education,Culture,Sports,Science and Technology of Japan,No.25K10147.
文摘BACKGROUND Pancreatic neuroendocrine microtumors(PNEMTs)are small(<5 mm),nonfunctioning,well-differentiated neuroendocrine neoplasms.Although they are rare,they are not invariably benign.PNEMTs are typically discovered incidentally during autopsy.However,data regarding the occurrence of PNEMTs in the elderly population,particularly those identified incidentally in cadaveric studies,remain limited.AIM To investigate the prevalence and histopathological characteristics of PNEMTs in elderly individuals by analyzing cadaveric pancreatic tissues.METHODS We conducted a retrospective analysis of 85 pancreatic specimens(age range:58-109 years)obtained from cadavers for anatomical education and research at the Department of Life Dentistry,Nippon Dental University.Paraffin sections of the pancreatic head,body,and tail were prepared for histological and immunohistochemical analysis.RESULTS Five cases with PNEMTs(5/85,5.9%;male,n=33;female,n=52;mean age:85.8±12.1 years)were identified.The tumors were solitary,well circumscribed,and located within the pancreatic parenchyma(body:n=4;tail:n=1),and all were<5 mm(range:0.54-2.20 mm)in size.All tumors showed strong chromogranin A and synaptophysin positivity,and were predominantly glucagon(GLU)-positive.Ki-67 immunostaining indicated minimal proliferative activity;therefore,these tumors were considered non-functioning,GLU-producing,well-differentiated grade 1 PNEMTs.CONCLUSION Small,predominantly low-grade,GLU-secreting PNEMTs were present in 5.9%of elderly individuals,highlighting the prevalence of subclinical PNEMTs and the need for careful follow-up.
