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Immunohistochemical and mutational analysis of c-kit in gastrointestinal neuroendocrine cell carcinoma
Tsutomu Ishikubo1, Kiwamu Akagi, Masafumi Kurosumi
1Division of Molecular Diagnosis and Cancer Prevention, Saitama Cancer Center, Kitaadachigun, Saitama 362-0806, Japan.
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.
Insights
Gastrointestinal neuroendocrine cell carcinoma (NEC) shows c-kit expression, similar to lung NEC. This suggests c-kit inhibitors may offer a new therapy for these aggressive gastrointestinal tumors.
Area of Science:
- Oncology
- Gastroenterology
- Molecular Biology
Background:
- Gastrointestinal neuroendocrine cell carcinoma (NEC) is an aggressive malignancy with limited therapeutic options.
- Gastrointestinal stromal tumors (GIST) respond well to c-kit inhibitors, with frequent c-kit mutations.
- Pulmonary NEC also expresses c-kit, showing sensitivity to c-kit inhibitors in vitro.
Purpose of the Study:
- To investigate the expression and mutation status of c-kit in gastrointestinal NEC.
- To determine if c-kit targeted therapy could be a viable treatment option for gastrointestinal NEC.
Main Methods:
- Analysis of surgically resected gastrointestinal NEC samples.
- Immunohistochemistry and RT-PCR to assess c-kit protein and gene expression.
- Single-strand conformation polymorphism (SSCP) to detect c-kit gene mutations.
Main Results:
- c-kit protein was expressed in 26% (6/23) of gastrointestinal NEC cases.
- Expression varied by tumor location: 25% colorectal, 50% duodenal, 25% gastric.
- No c-kit gene mutations were detected in any gastrointestinal NEC samples.
Conclusions:
- Gastrointestinal NEC exhibits c-kit expression frequencies comparable to pulmonary NEC.
- The findings support the potential efficacy of c-kit inhibitors for treating a subset of gastrointestinal NEC.
- Further research into c-kit targeted therapies for gastrointestinal NEC is warranted.
