Gastrointestinal Stromal Tumors, Identification of C-Kit Mutation and Differential Diagnosis

Abstract

Background: Prior to the recognition of C-Kit mutations, GIST were most commonly classified as leiomyoma, leiomyosarcoma, leiomyoblastoma or Autonomic nervous system gastrointestinal tumor. This is why, for the accurate histologic diagnosis of these tumors, it is necessary to record the C-Kit mutation and to identify some other molecular markers that help in differential diagnosis. C-Kit mutation detection is a criterion for morphologic diagnosis and also it serves as a predictive factor for determining the therapy with Imatinib (Glivec) if it is present in these tumors.Objectives: Evaluation of 49 cases of C-Kit mutations and differential diagnosis assessment by IHC examinations.Material and Methods: The study is a retrospective cohort type. 49 patients was evaluated the C-Kit mutation and further IHC examinations for differential diagnosis with other similar lesions. For this purpose the immunoreactivity for CD117, CD34, Actin, Desmin, S100 was evaluated. In these cases, the proliferative index with Ki67 was also evaluated as a prognostic factor together with the tumor diameter and presence or not of necrosis.Results: In the cases studied the presence of c-kit mutation (CD117 positive) was detected in 97% of the examined cases, CD34 was found positive in 77% of the examined cases, SMA was found positive in 34% of the examined cases, Desmin was found positive in 17% of the examined cases, S100 was found positive in 7% of the examined cases. Ki67 resulted to be on average 17.6% in cases with mitotic index> 5/50 HPF and on average 5.7% in cases with mitotic index <5/50% HPF Conclusions: Most of the mesenchymal tumors in the gastrointestinal system are Gastrointestinal Stromal type. This tumor is diagnosed in most cases if C-Kit mutation (positive immunoreactivity for CD117) is identified. Other immunostains like CD34, SMA, Desmin,  S100, help in the diagnose by differentiating this tumor from other histologically similar lesions. Proliferative index determination by Ki67 serves for the differentiation of these tumors into two prognostic categories.

Keywords: GIST, C-KIT mutations, differential diagnosis, malignant behavior