Human epidermal growth factor receptor (HER) family members and insulin-like growth factor 1 receptor (IGF1R) have received considerable attention as potential targets for cancer therapy. The aim of this study was to characterize the clinicopathological and molecular signifi cance of expression of HER family members and IGF1R in gastric cancer. We analyzed 217 formalin-fi xed, paraffi nembedded gastric cancer tissue specimens from Japanese patients who had undergone surgical treatment. Expression of HER1, HER3,HER4, IGF1R and p53 were analyzed by immunohistochemistry. The results were compared with clinicopathological and molecular characteristics including expression of HER2 and phospho-Akt, phosphatidylinositol 3-kinase, catalytic, alpha polypeptide (PIK3CA)mutations, Epstein-Barr virus (EBV) infection and microsatellite instability. HER1 expression was found in 54 (25%) of 217 cases and was signifi cantly correlated with intestinal histological type, depth of invasion, advanced stage and poor prognosis. Membranous and/or cytoplasmic HER3 expression was found in 113 cases (52%) and was signifi cantly correlated with depth of invasion, advanced stage and poor prognosis. Membranous and/or cytoplasmic HER4 expression was found in 126 cases (58%) but was not signifi cantly correlated with any parameters. Membranous IGF1R expression was found in 91 cases (42%) and was signifi cantly correlated with intestinal histological type, lymph node metastasis and advanced stage. Expression of HER3 and IGF1R was correlated with pAkt expression.Expression of HER1 and HER3 was observed less frequently in EBV+ cancers than in EBV- cancers. HER3 expression was also an independent prognostic factor. The results suggest that expression of HER1, HER3 and IGF1R plays important roles in gastric cancer.Simultaneous targeting of multiple HERs and IGF-IR may be a useful new strategy for antineoplastic treatment.
Hiroaki et al. (2017) studied this question.