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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 5/2013

01-05-2013 | Hepatobiliary Tumors

Regional Differences in Gallbladder Cancer Pathogenesis: Insights from a Comparison of Cell Cycle-Regulatory, PI3K, and Pro-Angiogenic Protein Expression

Authors: Jean M. Butte, MD, Javiera Torres, MD, Emanuela F. Veras, MD, Kenichi Matsuo, MD, Mithat Gönen, PhD, Michael I. D’Angelica, MD, Enrique Waugh, MD, Manuel Meneses, MD, Yoshiyaki Inayama, MD, Yuman Fong, MD, Ronald P. DeMatteo, MD, Hernan De La Fuente, MD, Itaru Endo, MD, David S. Klimstra, MD, William R. Jarnagin, MD

Published in: Annals of Surgical Oncology | Issue 5/2013

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Abstract

Background

The variable incidence of gallbladder cancer (GBCA) suggests regional pathogenetic differences. This study compares cell cycle-regulatory, angiogenesis-related, and PI3K pathway protein expression in GBCAs from three continents.

Methods

Immunohistochemical expression of several proteins was assessed, correlated with clinicopathologic variables, and compared among centers from Chile (Fundación Arturo López Pérez [FALP]), Japan (Yokohama City University [YCU]), and the United States (Memorial Sloan-Kettering Cancer Center [MSKCC]). Hierarchical clustering was used to partition the data based on protein-expression and treatment center.

Results

Tissue from 117 patients (MSKCC = 76; FALP = 22; YCU = 19) was analyzed. Mdm2 overexpression was seen only at MSKCC (p < 0.0001). Absence of p21 (p = 0.03) and VEGFR2 (p = 0.018) were more common and p27 expression was less frequent (p = 0.047) in tumors from YCU. Ki-67 labeling index in YCU tumors (median = 10) was two-thirds lower than at other centers. On hierarchical clustering analysis, all YCU patients (p = 0.017) and those with early tumors (p = 0.017) clustered separately from MSKCC. Median disease-specific survival after curative intent (R0) resection was 27 months and was similar among centers (p = 0.9). Median disease-specific survival of patients with early tumors was 28.4 months and was higher at YCU (not reached, p = 0.06).

Conclusions

Cell cycle-regulatory protein expression patterns of YCU tumors differed from those treated at FALP and MSKCC. The differential clustering of protein expression and survival in patients with early tumors suggest regional differences in pathogenesis and disease biology.
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Metadata
Title
Regional Differences in Gallbladder Cancer Pathogenesis: Insights from a Comparison of Cell Cycle-Regulatory, PI3K, and Pro-Angiogenic Protein Expression
Authors
Jean M. Butte, MD
Javiera Torres, MD
Emanuela F. Veras, MD
Kenichi Matsuo, MD
Mithat Gönen, PhD
Michael I. D’Angelica, MD
Enrique Waugh, MD
Manuel Meneses, MD
Yoshiyaki Inayama, MD
Yuman Fong, MD
Ronald P. DeMatteo, MD
Hernan De La Fuente, MD
Itaru Endo, MD
David S. Klimstra, MD
William R. Jarnagin, MD
Publication date
01-05-2013
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 5/2013
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-012-2761-0

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