Regional differences in gallbladder cancer pathogenesis

Insights from a comparison of cell cycle-regulatory, PI3K, and pro-angiogenic protein expression

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1470-1481
Number of pages12
JournalAnnals of Surgical Oncology
Volume20
Issue number5
DOIs
StatePublished - May 2013
Externally publishedYes

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Angiogenic Proteins
Gallbladder Neoplasms
Phosphatidylinositol 3-Kinases
Cell Cycle
Neoplasms
Cluster Analysis
Survival
Proteins
Cell Cycle Proteins
Chile

ASJC Scopus subject areas

  • Surgery
  • Oncology

Cite this

Regional differences in gallbladder cancer pathogenesis : Insights from a comparison of cell cycle-regulatory, PI3K, and pro-angiogenic protein expression. / Butte, Jean M.; Torres, Javiera; Veras, Emanuela F.; Matsuo, Kenichi; Gönen, Mithat; D'Angelica, Michael I.; Waugh, Enrique; Meneses, Manuel; Inayama, Yoshiyaki; Fong, Yuman; Dematteo, Ronald P.; De La Fuente, Hernan; Endo, Itaru; Klimstra, David S.; Jarnagin, William R.

In: Annals of Surgical Oncology, Vol. 20, No. 5, 05.2013, p. 1470-1481.

Research output: Contribution to journalArticle

Butte, JM, Torres, J, Veras, EF, Matsuo, K, Gönen, M, D'Angelica, MI, Waugh, E, Meneses, M, Inayama, Y, Fong, Y, Dematteo, RP, De La Fuente, H, Endo, I, Klimstra, DS & Jarnagin, WR 2013, 'Regional differences in gallbladder cancer pathogenesis: Insights from a comparison of cell cycle-regulatory, PI3K, and pro-angiogenic protein expression', Annals of Surgical Oncology, vol. 20, no. 5, pp. 1470-1481. https://doi.org/10.1245/s10434-012-2761-0
Butte, Jean M. ; Torres, Javiera ; Veras, Emanuela F. ; Matsuo, Kenichi ; Gönen, Mithat ; D'Angelica, Michael I. ; Waugh, Enrique ; Meneses, Manuel ; Inayama, Yoshiyaki ; Fong, Yuman ; Dematteo, Ronald P. ; De La Fuente, Hernan ; Endo, Itaru ; Klimstra, David S. ; Jarnagin, William R. / Regional differences in gallbladder cancer pathogenesis : Insights from a comparison of cell cycle-regulatory, PI3K, and pro-angiogenic protein expression. In: Annals of Surgical Oncology. 2013 ; Vol. 20, No. 5. pp. 1470-1481.
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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 (Fundaci{\'o}n Arturo L{\'o}pez P{\'e}rez [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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T1 - Regional differences in gallbladder cancer pathogenesis

T2 - Insights from a comparison of cell cycle-regulatory, PI3K, and pro-angiogenic protein expression

AU - Butte, Jean M.

AU - Torres, Javiera

AU - Veras, Emanuela F.

AU - Matsuo, Kenichi

AU - Gönen, Mithat

AU - D'Angelica, Michael I.

AU - Waugh, Enrique

AU - Meneses, Manuel

AU - Inayama, Yoshiyaki

AU - Fong, Yuman

AU - Dematteo, Ronald P.

AU - De La Fuente, Hernan

AU - Endo, Itaru

AU - Klimstra, David S.

AU - Jarnagin, William R.

PY - 2013/5

Y1 - 2013/5

N2 - 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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