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Japanese Journal of Clinical Oncology Advance Access published online on July 14, 2006
Japanese Journal of Clinical Oncology, doi:10.1093/jjco/hyl061
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© 2006 Foundation for Promotion of Cancer Research
Received December 16, 2005
Accepted May 10, 2006

Original Article

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

Tsutomu Ishikubo 1, Kiwamu Akagi 1 *, Masafumi Kurosumi 2, Kensei Yamaguchi 1, Takahiro Fujimoto 1, Hirohiko Sakamoto 3, Yoichi Tanaka 3, and Atsushi Ochiai 4

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

* To whom correspondence should be addressed.
Kiwamu Akagi, E-mail: Akagi{at}cancer-c.pref.saitama.jp


  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.

Keywords: c-kit; gastrointestinal neuroendocrine cell carcinoma; c-kit inhibitor.
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