Overexpression of Ephrin A2 Receptors in Cancer Stromal Cells is a Prognostic Factor for the Relapse of Gastric Cancer

Overview

Journal Gastric Cancer

Specialties Gastroenterology
Oncology

Date 2014 Jun 9

PMID 24908114

Citations 10

Authors

Shojiro Kikuchi

Nobuaki Kaibe

Koji Morimoto

Hirokazu Fukui

Hirotaka Niwa

Yoshihiro Maeyama

Masashi Takemura

Masaki Matsumoto

Shoji Nakamori

Hiroto Miwa

Seiichi Hirota

Mitsuru Sasako

Affiliations

Soon will be listed here.

Abstract

Background: Microenvironments control cancer growth and progression. We explored the prognostic impact of stromal reaction and cancer stromal cells on relapse risk and survival after curative gastrectomy in gastric cancer patients.

Methods: Tissue samples were obtained from 107 patients with gastric adenocarcinoma who underwent curative (R0) gastrectomy. Primary stromal cells isolated from gastric cancer tissue (GCSC) and normal gastric tissue (Gastric stromal cell: GSC) in each patient were cultured and subjected to comprehensive proteome (LC-MS/MS) and real-time RT-PCR analysis. Expression of Ephrin A2 receptors (EphA2) in cancers and GCSC was evaluated immunohistochemically. Intermingling of EphA2-positive cancer cells and GCSC (IC/A2+) and overexpression of EphA2 in cancer cells (Ca/A2+) in invasive parts of tumors were assessed, as were relationships of IC/A2+, Ca/A2+, and clinicopathological factors with relapse-free survival and overall survival.

Results: Proteome analysis showed that EphA2 expression was significantly higher in GCSC than GSC. Real-time RT-PCR analysis showed that levels of EphA1/A2/A3/A5 and EphB2/B4 were ≥2.0-fold higher in GCSC than GSC. Ca/A2 and IC/A2 were positive in 65 (60.7 %) and 26 (24.3 %) patients, respectively. Relapse was significantly more frequent in IC/A2-positive than in IC/A2-negative (HR, 2.12; 95 % CI, 1.16-5.41; p = 0.0207) patients. Among the 54 patients who received S-1 adjuvant chemotherapy, relapse-free survival (RFS) was significantly shorter in those who were IC/A2-positive than in those who were IC/A2-negative and Ca/A2-negative (HR, 2.83; 95 % CI, 1.12-12.12; p = 0.0339). Multivariable analysis indicated that pathological stage (p = 0.010) and IC/A2+ (p = 0.008) were independent risk factors for recurrence.

Conclusion: IC/A2+ was predictive of relapse after curative (R0) gastrectomy.

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