Immunohistochemical demonstration of c-Kit protooncogene product in gallbladder cancer.

OBJECTIVE

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.