Immunohistochemical expression of receptor-tyrosine-kinase in patients with gastric cancer: A multicenter study in Japan.

Abstract

41 Background: Treatment of HER2 positive gastric cancer (GC) with trastuzumab, receptor-tyrosine-kinase (RTK) inhibitor, has led to significant gains in overall survival. Several other targeted therapies are currently undergoing preclinical and clinical testing in some malignancies and GC, directed against diverse oncogenic RTK, therefor it is important to define the expression pattern of target RTK in GC. A multicenter retrospective study was conducted to evaluate the correlation between the expression of some RTKs, HER2, EGFR and c-KIT, and clinicopathological features in GC. Methods: A total of 153 cases with GC which was surgically resected between 2000 and 2006 were registered from nine hospitals. The neoadjuvant treatment cases were excluded. Tumors were centrally examined for HER2, EGFR and c-KIT status with immunohistochemistry (IHC) and fluorescence in-situ hybridization (FISH) for HER2. The relation between the expressions of HER2, EGFR and c-KIT and clinicopathological factors was examined by Fisher’s exact test. The hazard ratio (HR) for death was estimated, and overall survivals (OS) were compared between positive and negative cases of HER2, EGFR, and c-KIT using log-rank test. Results: The proportion of positive cases with IHC of HER2, EGFR and c-KIT was 7.8%, 14.4% and 11.1%, respectively. There was no significant correlation between the expression of HER2, EGFR and c-KIT and differentiation, location and depth. HER2-positive cases tended to be more frequent in differentiated type tumors. EGFR-positve cases were more frequent in lymph node metastasis (P=0.013). c-KIT-positive cases tended to be more frequent in T1-T2 tumors. OS in HER2-positive cases were clearly worse than in HER2-negative cases (HR 2.23 (95%CI, 1.16-4.38); P=0.014). EGFR-positive cases had a tendency to be worse than in EGFR-negative cases (HR 1.60 (95%CI, 0.94-2.71); P=0.082). c-KIT-negative cases were worse than in c-KIT-positive cases (HR 0.42 (95%CI, 0.17-1.02); P=0.048). Conclusions: This study showed that HER2 expression is a factor of poor prognosis and that EGFR-positive status and c-KIT-negative status tended to be associated with worse outcomes in resected GC.