Background: This study assessed the human epidermal growth factor receptor-2 (HER2) protein expression, its relationship with gene amplification and its intra-tumoral heterogeneity in diffuse-gastric carcinoma, a subset of gastric carcinoma that might benefit from Trastuzumab in case of HER2 amplification according to recently reported ToGA trial (J Clin Oncol 27:18s, 2009 (suppl; abstr LBA4509)

Patients and methods: The study included 51 European consecutive patients who underwent surgical resection in our institution between January 1991 and December 2007 for diffuse gastric carcinoma. A tissue-microarray was constructed using paraffin-embedded tissues of gastrectomy and matched lymph nodes. HER2 were evaluated by immunohistochemistry (IHC), using the same criteria than for breast cancer. All samples with a 2+ or 3+ HER2 overexpression were evaluated by FISH.

Results: HER2 overexpression was observed in 2 (4%) tumors and there was intratumoral heterogeneity. The first tumour shows 2+/3+ immunostaining in lymph nodes with negative immunostaining in the primary tumor. The second tumor shows a focal 3+ HER2 immunostaining in the primary tumor without evidence of positive immunostaining in lymph nodes and peritoneal metastasis. Using FISH, HER2 3+ tumour areas had a gene amplification, whereas no amplification was found in 2+ tumor. The 2 HER2 positive tumors showed the same heterogeneous pattern, with adjacent 3+ positive and negative areas by both IHC and FISH. There was a 100% concordance between TMA and the tissue-sections. Despite complete resection, the 2 patients with HER2 expression died within 15 months.

Conclusions: This study showed that 4% of resected diffuse gastric carcinoma had a heterogeneous distribution of HER2 gene amplification. These findings raise the question whether HER2 testing should be realized systematically in these patients and whether Trastuzumab may benefit in tumours with heterogeneous HER2 expression.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4154.