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Tsutomu Ishikubo, Kiwamu Akagi, Masafumi Kurosumi, Kensei Yamaguchi, Takahiro Fujimoto, Hirohiko Sakamoto, Yoichi Tanaka, Atsushi Ochiai, Immunohistochemical and Mutational Analysis of c-kit in Gastrointestinal Neuroendocrine Cell Carcinoma, Japanese Journal of Clinical Oncology, Volume 36, Issue 8, August 2006, Pages 494–498, https://doi.org/10.1093/jjco/hyl061
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Abstract
Background: Gastrointestinal neuroendocrine cell carcinoma (NEC) is a highly aggressive tumor with poor prognosis, for which an effective therapy is highly desirable. Recently, use of a c-kit inhibitor achieved excellent results against gastrointestinal stromal tumor (GIST) that showed c-kit overexpression and mutation in most cases. According to recent studies, 17–44% of pulmonary NEC also expressed c-kit and the antitumor effect of c-kit inhibitor was demonstrated in vitro against small cell carcinoma of the lung. As gastrointestinal NECs are clinicopathologically similar to pulmonary NECs, we investigated c-kit expression and mutation in gastrointestinal NEC.
Methods: Surgically resected gastrointestinal NEC was examined for c-kit expression by immunohistochemistry and RT–PCR. Mutation of the c-kit gene was also investigated by means of single-strand conformation polymorphisms (SSCP).
Results: Twenty-six percent (6 out of 23 patients) of gastrointestinal NEC expressed c-kit protein. c-kit protein expression was demonstrated in 1 out of 4 colorectal, 1 out of 2 duodenal, 4 out of 16 gastric and no esophageal (sample size of 1) NECs. The results of immunohistochemistry for c-kit were consistent with the RT–PCR. No c-kit gene mutation was found in gastrointestinal NEC.
Conclusion: The frequency of c-kit expression in gastrointestinal NEC was similar to that previously reported for pulmonary NEC. These findings suggest that c-kit inhibitor may be effective against some gastrointestinal NECs.
