Clinical implications of C-kit gene mutation in patients with large gastrointestinal stromal tumors.

BACKGROUND AND AIM: To evaluate the clinical implications of C-kit gene mutation in patients with gastrointestinal stromal tumors (GIST) greater than 10 cm in size. METHODS: All cases of pathologically diagnosed GIST with positive CD117 immunostaining from one hospital were retrospectively reviewed. Tissue from the 25 patients with tumors greater than 10 cm in diameter were collected and DNA was extracted. Exons 9, 11, and 13 of the C-kit gene were analyzed and the mutations compared with the clinical and pathological characteristics of the corresponding tumors. RESULTS: Of the 25 tumors studied, 16 had C-kit gene mutations and nine did not. Of the 16 with mutations, there were four with exon 9 mutations, 12 with exon 11 mutations, and none with exon 13 mutations. Gene mutations were more frequent in male than female patients (12/13, 92% vs 4/12, 33%). There were no significant differences in age, resectability, recurrence rate, tumor characteristics (ulceration, necrosis, hemorrhage and mitotic counts), or survival in patients with or without gene mutations. CONCLUSIONS: C-kit gene mutations were frequently found in patients with large GIST, more commonly in men than in women. However, the presence of a mutation was not predictive of prognosis in patients with large GIST.

Clinical manifestations and prognostic factors in patients with gastrointestinal stromal tumors.

AIM: To investigate the incidence of CD117-positive immunohistochemical staining in previously diagnosed gastrointestinal (GI) tract stromal tumors (GIST) and to analyze the tumors' clinical manifestations and prognostic factors. METHODS: We retrospectively reviewed 91 cases with a previous diagnosis of GI stromal tumor, leiomyoma, or leiomyosarcoma. Tissue samples were assessed with CD117, CD34, SMA and S100 immunohistochemical staining. Clinical and pathological characteristics were analyzed for prognostic factors. RESULTS: CD117 was positive in 81 (89%) of 91 tissue samples. There were 59 cases (72.8%) positive for CD34, 13 (16%) positive for SMA, and 12 (14.8%) positive for S100. There was no gender difference in patients with CD117-positive GIST. Their mean age was 65 years. There were 44 (54%) tumors located in the stomach and 29 (36%) in the small intestine. The most frequent presenting symptoms were abdominal pain and GI bleeding. The mean tumor size was 7.5 +/- 5.7 cm. There were 35 cases (43.2%) with tumors >5 cm. The tumor size correlated significantly with tumor mitotic count and resectability. Tumor size, mitotic count, and resectability correlated significantly with tumor recurrence and survival. There was recurrent disease in 39% of our patients, and their mean survival after recurrence was 16.6 months. Most recurrences were at the primary site or metastatic to the liver. Twenty-six percent of our patients died of their disease. CONCLUSION: Traditional histologic criteria are not specific enough to diagnose GIST. This diagnosis must be confirmed with CD117 immunohistochemical staining. Prognosis is dependent on tumor size, mitotic count, and resectability.