HER-2/neu Overexpression is an Independent Prognostic Factor for Intestinal-type and Early-stage Gastric Cancer Patients

Goals: To evaluate the HER-2/neu protein level by immunohistochemistry (IHC) and its gene amplification by fluorescence in situ hybridization (FISH) in gastric cancer samples, and the relevance to the prognosis of gastric cancer patients. Study: HER-2/neu overexpression and gene amplification were examined with semiquantitative standardized IHC in 775 formalin-fixed paraffin-embedded gastric cancer samples, and 252 of these cases were analyzed with FISH. Results: Of the 775 gastric cancer samples examined by IHC, a total of 88 (11%) cases were positive for HER-2/neu overexpression at a score of 3+; another 44 (6%) cases were equivocal with a score of 2+; and the rest 643 (83%) cases were negative scored as 0/1+. Intestinal-type and early-stage cancers exhibited higher rate of HER-2/neu overexpression than those of diffuse/mixed-type and advanced cancers (P < 0.05). Intestinal-type and early-stage cancers with HER-2/neu overexpression also exhibited short 5 year survival rates (21% vs. 47%, P = 0.027; 29% vs. 60%, P = 0.037) than HER-2/neu-negative cases, but not in the diffuse/mixed-type and advanced stage cancers. By FISH analysis, it was shown that 70% (60/86) of IHC 3+ had HER-2/neu gene amplication. In contrast, only 14% (6/43) of IHC 2+ cases, and 2.5% (3) of the 120 cases with IHC 0/1+ randomly selected showed HER-2/neu gene amplification. Conclusions: HER-2/neu overexpression may be used as an independent prognostic factor for intestinal-type and early-stage gastric cancer patients. IHC 3+ and 2+ cases should be further detected by FISH to assess HER-2/neu gene status. Patients with HER-2/neu amplification also might constitute potential candidates for targeted therapy with trastuzumab.