A Validation Study for Recurrence Risk Stratification of Stage II Colon Cancer Using the 55-Gene Classifier.

Shinto, Eiji; Oki, Eiji; Shimokawa, Mototsugu; Yamaguchi, Shigeki; Ishiguro, Megumi; Morita, Masaru; Kusumoto, Tetsuya; Tomita, Naohiro; Hashiguchi, Yojiro; Tanaka, Masafumi; Ohnuma, Shinobu; Tada, Sachiyo; Matsushima, Tomoko; Hase, Kazuo

INTRODUCTION DNA microarrays, such as the consensus molecular subtype (CMS) classification using >600 genes, are used to predict cancer patient prognosis. We recently constructed a simple 55-gene classifier (55GC) system to risk stratify colon cancer (CC). OBJECTIVE Here, we validate the 55GC specifically for stage II CC and compare it with CMS categories. METHODS Tissue sections from 232 stage II CC patients who underwent curative surgery without adjuvant chemotherapy between 2009 and 2012 were subjected to DNA microarray analysis. RESULTS Based on the 55GC, patients were classified into microsatellite instability-like (27%), chromosomal instability-like (41%), and stromal (32%) subtypes with 5-year relapse-free survival (RFS) rates of 88.5, 83.3, and 71.2%, respectively (stromal vs. others: p = 0.0049). Multivariate analysis by Cox's proportional hazard model revealed that the stromal subtype, pT4, and the number of lymph nodes examined (<12) were independent poor prognostic factors. The overall concordance rate between 55GC and CMS was 72%, and 5-year RFS rates of patients with CMS1, CMS2, CMS3, and CMS4 cancers were 100, 85.5, 92.3, and 73.0%, respectively (p = 0.0113). CONCLUSIONS We conclude that the 55GC is a useful and reproducible grading system for stage II CC recurrence risk stratification.