Open AccessImmunohistochemical analysis of RTK s expression identified HER 3 as a prognostic indicator of gastric cancer
Author(s) -
Ema Akira,
Yamashita Keishi,
Ushiku Hideki,
Kojo Ken,
Minatani Naoko,
Kikuchi Mariko,
Mieno Hiroaki,
Moriya Hiromitsu,
Hosoda Kei,
Katada Natsuya,
Kikuchi Shiro,
Watanabe Masahiko
Publication year - 2014
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12556
Subject(s) - immunohistochemistry , medicine , stage (stratigraphy) , cancer , hazard ratio , proportional hazards model , oncology , multivariate analysis , survival analysis , eph receptor a2 , gastroenterology , pathology , receptor tyrosine kinase , receptor , biology , confidence interval , paleontology
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 ( RTK s) has repeatedly represented poor prognosis for cancers. However it has not been demonstrated whether RTK s 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 RTK s including EGFR , HER 2, HER 3, IGF ‐1R, and EphA2 was analyzed using immunohistochemistry ( IHC ). Analysis using a multivariate proportional hazard model identified the most significant RTK s that represented independent prognostic relevance. When tumor HER 3 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 HER 2 expression. Intriguingly, HER 3 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 HER 3 ( 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 HER 3‐positive. Thus, of the RTK s studied, HER 3 was the only RTK identified as an independent prognostic indicator of stage II / III advanced gastric cancer with standard treatment.