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Japanese Journal of Clinical Oncology Advance Access originally published online on July 14, 2006
Japanese Journal of Clinical Oncology 2006 36(8):494-498; doi:10.1093/jjco/hyl061
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© 2006 Foundation for Promotion of Cancer Research

Immunohistochemical and Mutational Analysis of c-kit in Gastrointestinal Neuroendocrine Cell Carcinoma

Tsutomu Ishikubo1, Kiwamu Akagi1, Masafumi Kurosumi2, Kensei Yamaguchi1, Takahiro Fujimoto1, Hirohiko Sakamoto3, Yoichi Tanaka3 and Atsushi Ochiai4

1 Division of Molecular Diagnosis and Cancer Prevention, 2 Division of Pathology, 3 Division of Gastroenterological Surgery, Saitama Cancer Center, Kitaadachigun, Saitama and 4 Pathology Division, Innovative Medical Research Center, National Cancer Center Hospital East, Chiba, Japan

For reprints and all correspondence: Kiwamu Akagi, Division of Molecular Diagnosis and Cancer Prevention, Saitama Cancer Center, 818 Komuro Ina, Kitaadachigun, Saitama 362-0806, Japan. E-mail: Akagi{at}cancer-c.pref.saitama.jp

Received December 16, 2005; accepted May 10, 2006

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.

Key Words: c-kit • gastrointestinal neuroendocrine cell carcinoma • c-kit inhibitor


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