Immunohistochemical analysis of RTKs expression identified HER3 as a prognostic indicator of gastric cancer

Cancer Science

Akira Ema¹  Keishi Yamashita¹  Hideki Ushiku¹  Ken Kojo¹  Naoko Minatani¹  Mariko Kikuchi¹  Hiroaki Mieno¹  Hiromitsu Moriya¹  Kei Hosoda¹  Natsuya Katada¹  Shiro Kikuchi¹ 

[1] Department of Surgery, Kitasato University School of Medicine, Minami-ku, Sagamihara, Kanagawa, Japan

关键词: Advanced gastric cancer;    HER3;    prognosis;    receptor type tyrosine kinases (RTKs);    S‐1;   

DOI  :  10.1111/cas.12556

来源: Wiley

【 摘 要 】

Abstract

Standard treatment in Japan for the 13th Japanese Gastric Cancer Association stage II/III advanced gastric cancer is postoperative adjuvant S-1 administration after curative surgery. High expression of receptor type tyrosine kinases (RTKs) has repeatedly represented poor prognosis for cancers. However it has not been demonstrated whether RTKs have prognostic relevance for stage II/III gastric cancer with standard treatment. Tumor tissues were obtained from 167 stage II/III advanced gastric cancer patients who underwent curative surgery and received postoperative S-1 chemotherapy from 2000 to 2010. Expression of the RTKs including EGFR, HER2, HER3, IGF-1R, and EphA2 was analyzed using immunohistochemistry (IHC). Analysis using a multivariate proportional hazard model identified the most significant RTKs that represented independent prognostic relevance. When tumor HER3 expression was classified into IHC 1+/2+ (n = 98) and IHC 0 (n = 69), the cumulative 5-year Relapse Free Survival (5y-RFS) was 56.5 and 82.9%, respectively (P = 0.0034). Significant prognostic relevance was similarly confirmed for IGF-1R (P = 0.014), and EGFR (P = 0.030), but not for EphA2 or HER2 expression. Intriguingly, HER3 expression was closely correlated with IGF-1R (P < 0.0001, R = 0.41), and EphA2 (P < 0.0001, R = 0.34) expression. Multivariate proportional hazard model analysis identified HER3 (IHC 1+/2+) (HR; 1.53, 95% CI, 1.11–2.16, P = 0.0078) as the sole RTK that was a poor prognostic factor independent of stage. Of the 53 patients who recurred, 40 patients (75.5%) were HER3-positive. Thus, of the RTKs studied, HER3 was the only RTK identified as an independent prognostic indicator of stage II/III advanced gastric cancer with standard treatment.

【 授权许可】

CC BY-NC-ND   
© 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

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