RESUMO
BACKGROUND: Human epidermal growth factor receptor 2 (HER2) is related to the pathogenesis and poor outcome of numerous types of carcinomas, including gastric carcinoma. Gastric cancer patients with HER2 positivity have become potential candidates for targeted therapy with trastuzumab. METHODS: We investigated 208 gastric cancer specimens using immunohistochemistry (IHC), fluorescence in situ hybridization and dual in situ hybridization (ISH). We also investigated the concordance between IHC and ISH. The correlation between HER2 status and various clinicopathological findings was also investigated. RESULTS: In total, 15.9% (33/208) and 24.5% (51/208) of gastric cancers showed HER2 gene amplification and protein overexpression, respectively. A high level of concordance between ISH and IHC analyses (91.3%, κ = 0.76) was found. A significant correlation between HER2 status and intestinal-type (p < .05) and differentiated carcinomas (p < .05) was also noted. The HER2 heterogeneity was high in gastric cancers; we found 68.8% phenotypic heterogeneity and 57.6% genotypic heterogeneity. Heterogeneity in HER2 protein expression and gene amplification showed a close association with diffuse histologic type and IHC 2+. CONCLUSIONS: HER2 protein overexpression and gene amplification were detected in 24.5% and 15.9% of gastric cancer specimens, respectively. Intestinal-type showed a higher level of HER2 protein overexpression and gene amplification than diffuse type. HER2 status also showed a significant relationship with well- and moderately-differentiated carcinomas. The ratio of phenotypic and genotypic heterogeneity of HER2 was high in gastric carcinomas and was associated with HER2 IHC 2+ and diffuse histologic type.
Assuntos
Humanos , Povo Asiático , Fluorescência , Amplificação de Genes , Genes erbB-2 , Imuno-Histoquímica , Hibridização In Situ , Características da População , Receptores ErbB , Neoplasias Gástricas , TrastuzumabRESUMO
HER-2 is a biomarker participating in tumor cells biology that has been thoroughly studied in breast cancer, but it can also be overexpressed in other neoplasms like gastric cancer. In this setting there are more reported cases about HER-2 positive immunohistochemistry in intestinal subtype than in diffuse subtype; in those cases, staining is limited to basolateral membrane. Positivity may be verified through fluorescent hybridization. This case is about a 30-year-old man diagnosed with diffuse gastric carcinoma from a total gastrectomy surgical specimen, in which 3+ HER-2 immunohistochemistry is confirmed in the totality of the plasma membrane of mucosa cells and is sustained using fluorescent hybridization for HER-2.
HER-2 es un biomarcador que colabora con la biología de la célula tumoral y ha sido ampliamente estudiado en cáncer de mama, pero también puedesobreexpresarse en otras neoplasias como el cáncer gástrico. En este escenario se reportan más casos deinmunohistoquímica positiva por HER-2 en el subtipo intestinal con respecto al subtipo difuso; en dichos casos, la tinción se limita a la membrana basolateral. Los casos positivos pueden ser verificados a través de hibridación fluorescente in situ. Se presenta el casode un sujeto masculino de 30 años con diagnóstico de carcinoma gástrico difuso a través de un espécimenquirúrgico de gastrectomía total, a la cual se le confirma mediante inmunohistoquímica 3+ para HER-2 enla totalidad de la membrana celular de las células de la mucosa y corroborado utilizando la técnica hibridaciónfluorescente in situ para HER-2.