Histomolecular Phenotypes and Outcome in Adenocarcinoma of the Ampulla of Vater
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Published:2013-04-01
Issue:10
Volume:31
Page:1348-1356
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ISSN:0732-183X
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Container-title:Journal of Clinical Oncology
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language:en
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Short-container-title:JCO
Author:
Chang David K.1, Jamieson Nigel B.1, Johns Amber L.1, Scarlett Christopher J.1, Pajic Marina1, Chou Angela1, Pinese Mark1, Humphris Jeremy L.1, Jones Marc D.1, Toon Christopher1, Nagrial Adnan M.1, Chantrill Lorraine A.1, Chin Venessa T.1, Pinho Andreia V.1, Rooman Ilse1, Cowley Mark J.1, Wu Jianmin1, Mead R. Scott1, Colvin Emily K.1, Samra Jaswinder S.1, Corbo Vincenzo1, Bassi Claudio1, Falconi Massimo1, Lawlor Rita T.1, Crippa Stefano1, Sperandio Nicola1, Bersani Samantha1, Dickson Euan J.1, Mohamed Mohamed A.A.1, Oien Karin A.1, Foulis Alan K.1, Musgrove Elizabeth A.1, Sutherland Robert L.1, Kench James G.1, Carter C. Ross1, Gill Anthony J.1, Scarpa Aldo1, McKay Colin J.1, Biankin Andrew V.1
Affiliation:
1. David K. Chang, Amber L. Johns, Christopher J. Scarlett, Marina Pajic, Angela Chou, Mark Pinese, Jeremy L. Humphris, Marc D. Jones, Christopher Toon, Adnan M. Nagrial, Lorraine A. Chantrill, Venessa T. Chin, Andreia V. Pinho, Ilse Rooman, Mark J. Cowley, Jianmin Wu, R. Scott Mead, Emily K. Colvin, Elizabeth A. Musgrove, Robert L. Sutherland, James G. Kench, Anthony J. Gill, and Andrew V. Biankin, Kinghorn Cancer Centre and Garvan Institute of Medical Research; David K. Chang and Andrew V. Biankin,...
Abstract
Purpose Individuals with adenocarcinoma of the ampulla of Vater demonstrate a broad range of outcomes, presumably because these cancers may arise from any one of the three epithelia that converge at that location. This variability poses challenges for clinical decision making and the development of novel therapeutic strategies. Patients and Methods We assessed the potential clinical utility of histomolecular phenotypes defined using a combination of histopathology and protein expression (CDX2 and MUC1) in 208 patients from three independent cohorts who underwent surgical resection for adenocarcinoma of the ampulla of Vater. Results Histologic subtype and CDX2 and MUC1 expression were significant prognostic variables. Patients with a histomolecular pancreaticobiliary phenotype (CDX2 negative, MUC1 positive) segregated into a poor prognostic group in the training (hazard ratio [HR], 3.34; 95% CI, 1.69 to 6.62; P < .001) and both validation cohorts (HR, 5.65; 95% CI, 2.77 to 11.5; P < .001 and HR, 2.78; 95% CI, 1.25 to 7.17; P = .0119) compared with histomolecular nonpancreaticobiliary carcinomas. Further stratification by lymph node (LN) status defined three clinically relevant subgroups: one, patients with histomolecular nonpancreaticobiliary (intestinal) carcinoma without LN metastases who had an excellent prognosis; two, those with histomolecular pancreaticobiliary carcinoma with LN metastases who had a poor outcome; and three, the remainder of patients (nonpancreaticobiliary, LN positive or pancreaticobiliary, LN negative) who had an intermediate outcome. Conclusion Histopathologic and molecular criteria combine to define clinically relevant histomolecular phenotypes of adenocarcinoma of the ampulla of Vater and potentially represent distinct diseases with significant implications for current therapeutic strategies, the ability to interpret past clinical trials, and future trial design.
Publisher
American Society of Clinical Oncology (ASCO)
Subject
Cancer Research,Oncology
Cited by
134 articles.
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