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Immunohistochemical analysis of the Wnt/β-catenin signaling pathway in pancreatic neuroendocrine neoplasms

World Journal of Gastrointestinal Oncology 2016年第8期8卷 615-622页

作者： Vivian Weiss Julie Dueber Jesse P Wright Justin Cates Frank Revetta Alexander A Parikh nipun b merchant Chanjuan Shi Department of Pathology Microbiology and Immunology Vanderbilt University Medical Center Department of Surgery Surgical Oncology Vanderbilt University Medical Center Department of Surgery Surgical Oncology University of Miami Hospital

AIM: To investigate the role of the Wnt/β-catenin pathway in pancreatic neuroendocrine neoplasms(PanN ENs). METHODS: Tissue microarrays containing 88 PanN ENs were immunohistochemically labeled with antibodies to β-catenin, E-cadherin, adenomatous polyposis coli(APC), chromogranin and synaptophysin. One case had only metastatic tumors resected, whereas others(n = 87) received pancreatectomy with or without partial hepatectomy. Pathology slides, demographic, clinicopathologic, and follow up data were reviewed. Patients' demographics, clinicopathologic features, and immunohistochemical results from 87 primary tumors were compared between patients with low stage(stage Ⅰ/Ⅱ) and high stage(stage Ⅲ/Ⅳ) tumors. In addition, correlation of immunohistochemical results from primary tumors with disease-specific survival(DSS) was evaluated. RESULTS: Strong membranous β-catenin staining in the primary tumor was observed in all 13 stage Ⅲ/Ⅳ Pan NENs as compared to 47%(35/74) of stage Ⅰ/Ⅱtumors(P branous β-catenin staining was unassociated with tumor grade or DSS. Decreased membranous β-catenin staining was associated with decreased membranous E-cadherin labeling. Nuclear β-catenin staining was seen in 15%(2/13) of stage Ⅲ/Ⅳ Pan NENs as compared to 0%(0/74) of stage Ⅰ/Ⅱ tumors(P = 0.02). The case with metastasectomy only also showed nuclear β-catenin staining. Two of the three cases with nuclear β-catenin staining were familial adenomatous polyposis(FAP) patients. Lack of APC expression was seen in 70%(57/81) of the cases, including the 3 cases with nuclear β-catenin staining. Expression of E-cadherin and APC in primary tumor was not correlated with tumor grade, tumor stage, or disease specific survival. CONCLUSION: The Wnt/β-catenin pathway was altered in some PanN ENs, but did not Impact DSS. PanN ENs in FAP patients demonstrated nuclear β-catenin accumulation and loss of APC.

关键词： β-catenin Familial adenomatous polyposis Pancreatic neuroendocrine neoplasm Adenomatous polyposis coli E-cadherin

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Lymph node ratio and preoperative CA 19-9 levels predict overall survival and recurrence-free survival in patients with resected pancreatic adenocarcinoma

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World Journal of Gastrointestinal Oncology 2012年第10期4卷 207-215页

作者： Sabrina C Wentz Zhi-Guo Zhao Yu Shyr Chan-Juan Shi Kay Washington nipun b merchant Fen Xia A bapsi Chakravarthy Department of Pathology The Johns Hopkins HospitalBaltimoreMD 21201United States Department of biostatistics Vanderbilt University Medical CenterNashvilleTN 37215United States Department of Pathology Vanderbilt University Medical CenterNashvilleTN 37215United States Department of Surgery Vanderbilt University Medical CenterNashvilleTN 37215United States Department of Radiation Oncology Vanderbilt University Medical CenterNashvilleTN 37215United States

AIM:Clinicopathologic factors predicting overall survival (OS) would help identify a subset to benefit from adjuvant therapy. METHODS: One hundred and sixty-nine patients patients from 1984 to 2009 with curative resections for pancreatic adenocarcinoma were included. Tumors were staged by American Joint Committee on Cancer 7th edition criteria. Univariate and multivariable analyses were performed using Kaplan-Meier methodology or Cox proportional hazard models. Log-rank tests were performed. Statistical inferences were assessed by two-sided 5% significance level. RESULTS: Median age was 67.1 (57.2-73.0) years with equal gender distribution. Tumors were in the head (89.3%) or body/tail (10.7%). On univariate analysis, adjuvant therapy, lymph node (LN) ratio, histologic grade, negative margin status, absence of peripancreatic extension, and T stage were associated with improved OS. Adjuvant therapy, LN ratio, histologic grade, number of nodes examined, negative LN status, and absence of peripancreatic extension were associated with improved recurrence-free survival (RFS). On multivariable analysis, LN ratio and carbohydrate antigen (CA) 19-9 levels were associated with OS. LN ratio was associated with RFS. CONCLUSION: The LN ratio and CA 19-9 levels are independent prognostic factors following curative resections of pancreatic cancer.

关键词： Pancreatic adenocarcinoma Lymph node ratio Carbohydrate antigen 19-9 Recurrence-free survival Overall survival

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A pilot study of radiologic measures of abdominal adiposity:weighty contributors to early pancreatic carcinogenesis worth evaluating?

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Cancer biology & Medicine 2017年第1期14卷 66-73页

作者： Jennifer b.Permuth Jung W.Choi Dung-Tsa Chen Kun Jiang Gina DeNicola Jian-Nong Li Domenico Coppola barbara A.Centeno Anthony Magliocco Yoganand balagurunathan nipun merchant Jose G.Trevino Daniel Jeong Departments of Cancer Epidemiology Gastrointestinal Oncology Diagnostic Imaging and Interventional Radiology biostatistics and bioinformatics Anatomic Pathology Cancer Imaging and Metabolism Moffitt Cancer Center and Research InstituteTamPa 33612FLUSA Department of Surgery Sylvester Comprehensive Cancer Center at the University of Miami Miller School of MedicineMiami 33136FLUSA Department of Surgery Division of General SurgeryUniversity of Florida Health Sciences CenterGainesville 32611FLUSA

Objective:Intra-abdominal fat is a risk factor for pancreatic cancer(PC),but little is known about its contribution to PC precursors known as intraductal papillary mucinous neoplasms(IPMNs).Our goal was to evaluate quantitative radiologic measures of abdominal/visceral obesity as possible diagnostic markers of IPMN severity/***:In a cohort of 34 surgically-resected,pathologically-confirmed IPMNs(17 benign;17 malignant) with preoperative abdominal computed tomography(CT) images,we calculated body mass index(bMI) and four radiologic measures of obesity:total abdominal fat(TAF) area,visceral fat area(VFA),subcutaneous fat area(SFA),and visceral to subcutaneous fat ratio(V/S).Measures were compared between groups using Wilcoxon two-sample exact tests and other ***:Mean bMI for individuals with malignant IPMNs(28.9 kg/m^2) was higher than mean bMI for those with benign IPMNs(25.8 kg/m^2)(P=0.045).Mean VFA was higher for patients with malignant IPMNs(199.3 cm^2) compared to benign IPMNs(120.4cm^2),P=0.092.V/S was significantly higher(P=0.013) for patients with malignant versus benign IPMNs(1.25 vs.0.69 cm^2),especially among *** accuracy,sensitivity,specificity,and positive and negative predictive value of V/S in predicting malignant IPMN pathology were 74%,71%,76%,75%,and 72%,***:Preliminary findings suggest measures of visceral fat from routine medical images may help predict IPMN pathology,acting as potential noninvasive diagnostic adjuncts for management and targets for intervention that may be more biologically-relevant than *** investigation of gender-specific associations in larger,prospective IPMN cohorts is warranted to validate and expand upon these observations.

关键词： Abdominal obesity pre-malignant lesions pancreatic cancer computed tomography

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