Prognostic Relevance of p53 Overexpression in Gastrointestinal Stromal Tumors of the Small Intestine: Potential Implication for Adjuvant Treatment with Imatinib.

ABSTRACT

PURPOSE: Although genetic p53 aberrations are correlated with the prognosis of various types of cancer, their prognostic relevance is currently unclear in patients with gastrointestinal stromal tumors (GISTs) of the small intestine. METHODS: Between 1994 and 2008, 113 patients with resected localized GISTs of the small intestine were included in this analysis. Patients who received pre- and/or postoperative chemotherapy were excluded. p53 overexpression was assessed by immunohistochemical staining and defined as expression in >10 % of tumor cells. RESULTS: p53 overexpression was identified in 38 patients (34 %) and was significantly associated with epithelioid histology (p = 0.040) and high cellularity (p = 0.004). Relapse-free survival (RFS) significantly differed according to p53 overexpression (5-year RFS rates, 57 vs. 78 %; p = 0.005). By multivariate analysis, which included tumor necrosis, tumor size, mitotic count, and primary genotype, p53 overexpression significantly affected RFS with a hazard ratio of 3.50 (95 % confidence interval 1.48-8.25; p = 0.004). CONCLUSIONS: p53 overexpression is an independent prognostic factor in patients with small intestinal GISTs. This suggests that p53 expression can be used to further stratify recurrence risk in patients with resected GISTs of the small intestine.