Abstract

Background: ERBB2 expression in the primary tumor and its lymph node metastases varies in gastric cancer reflecting intratumoral heterogeneity. This finding also suggests that proliferation of a different clone in the metastatic nodes is possible. Methods: Seventy-four patients with gastric cancer who have undergone total or subtotal gastrectomy and found to have lymph node metastasis on pathologic examination were studied.47 (64%)were male and 27(34%) were female, with a median age of 58 (age range 29-87). All histologic sections were obtained from the gastrectomy and lymph node dissection specimens. ERBB2 status was evaluated by both IHC and SISH (silver in-situ hybridization). Disease-free survival and overall survival were also calculated according to ERBB2 expression. Results: SISH findings from the primary tumor were; SISH (-) n = 59 (80%), SISH (+) n = 15 (20%), while in the lymph nodes 56 (75%) patients were SISH negative and 18 (25%) patients were found to be SISH (+). In the primary tumor IHC findings were IHC 0 n = 42 (57%), IHC 1+ n = 9 (12%), IHC 2+ n = 3 (4%) and IHC 3+ in 19 patients (26%). The striking result was the discordance of ERBB2 status in 3 patients. In these three patients, ERBB2 expression was found to be positive in the metastatic lymph nodes while the primary tumor was ERBB2 –negative. Conclusion: As in breast cancer, a discrepancy of ERBB2 expression can occur between the primary tumor and its lymph node metastasis in gastric adenocarcinomas reflecting intratumoral heterogeneity. In order to predict trastuzumab benefit, ERBB2 status of lymph nodes should also be studied alongside of the primary tumor.

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