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Immunohistochemical demonstration of c‐Kit protooncogene product in gallbladder cancer
Author(s) -
Tanaka Shogo,
Tanaka Hiromu,
Yamamoto Takatsugu,
Shuto Taichi,
Takemura Shigekazu,
Hai Seikan,
Sakabe Katsu,
Uenishi Takahiro,
Hirohashi Kazuhiro,
Kubo Shoji
Publication year - 2006
Publication title -
journal of hepato‐biliary‐pancreatic surgery
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.63
H-Index - 60
eISSN - 1868-6982
pISSN - 0944-1166
DOI - 10.1007/s00534-005-1074-0
Subject(s) - gallbladder , cytokeratin , pathology , gallbladder cancer , carcinoma , immunohistochemistry , medicine , cd34 , immunostaining , adenocarcinoma , cancer , gastroenterology , biology , stem cell , genetics
Background/Purpose Although some gallbladder carcinomas are immunoreactive for c‐Kit, the reasons for the c‐Kit expression and its clinicopathologic implications are unknown. Methods We investigated the prevalence of c‐Kit immunoreactivity, its clinicopathologic correlates (including microvessel density and postoperative outcome), and the possible mechanisms of c‐Kit expression. We reviewed retrospectively, the clinicopathologic records of 47 patients who had undergone macroscopically complete gallbladder carcinoma resection. The numbers of patients at pathologic stages I to IV, according to current TNM‐based staging, were 10, 5, 18, and 14, respectively. For immunohistochemical examination, we used monoclonal antibodies against c‐Kit and CD 34 (progenitor cell markers), cytokeratin 7 and cytokeratin 19 (cholangiocyte markers), and OCH1E5 (a hepatocyte marker). Control tissue samples were from five gallbladder specimens each with chronic cholecystitis, polyp, and adenoma. Results Cytoplasmic immunostaining for c‐Kit was detected in 21 of the 47 gallbladder carcinomas (45%), and in 1 of the 15 control specimens (diagnosis, chronic cholecystitis). Young age was significantly associated with c‐Kit positivity; however, there were no significant differences in the incidence of c‐Kit positivity among other variables, including tumor stage and outcome. However, microvessel density was significantly higher in c‐Kit‐positive gallbladder carcinoma compared with c‐Kit‐negative gallbladder carcinoma. None of the 47 cancer specimens or the 15 control specimens were stained for CD34 and OCH1E5, but all 47 cancer specimens were stained for cytokeratins 7 and 19. Conclusions Gallbladder carcinomas positive for c‐Kit are unlikely to arise from immature cells, but may be associated with neovascularization. Angiogenesis inhibitors, such as tyrosine kinase inhibitors, therefore, may suppress the growth of some gallbladder cancers.