Regional differences in gallbladder cancer pathogenesis: Insights from a comparison of cell cycle-regulatory, PI3K, and pro-angiogenic protein expression Journal Article


Authors: Butte, J. M.; Torres, J.; Veras, E. F.; Matsuo, K.; Gonen, M.; D'Angelica, M. I.; Waugh, E.; Meneses, M.; Inayama, Y.; Fong, Y.; DeMatteo, R. P.; de la Fuente, H.; Endo, I.; Klimstra, D. S.; Jarnagin, W. R.
Article Title: Regional differences in gallbladder cancer pathogenesis: Insights from a comparison of cell cycle-regulatory, PI3K, and pro-angiogenic protein expression
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. © 2012 Society of Surgical Oncology.
Journal Title: Annals of Surgical Oncology
Volume: 20
Issue: 5
ISSN: 1068-9265
Publisher: Springer  
Date Published: 2013-05-01
Start Page: 1470
End Page: 1481
Language: English
DOI: 10.1245/s10434-012-2761-0
PROVIDER: scopus
PUBMED: 23212762
PMCID: PMC4048130
DOI/URL:
Notes: --- - "Export Date: 1 August 2013" - "CODEN: ASONF" - "Source: Scopus"
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MSK Authors
  1. Ronald P DeMatteo
    637 DeMatteo
  2. Mithat Gonen
    1028 Gonen
  3. Kenichi Matsuo
    5 Matsuo
  4. Emanuela Fernandes Tavora Veras
    20 Veras
  5. David S Klimstra
    978 Klimstra
  6. William R Jarnagin
    903 Jarnagin
  7. Yuman Fong
    775 Fong
  8. John Paul Torres
    6 Torres