187P - Ribonucleotide Reductase Subunit 2 (RRM2) Predicts Shorter Survival in Resected Stage I-III Non-Small Cell Lung Cancer (NSCLC) Patients

Abstract

ABSTRACT Background Biomarkers can help in identifying patients (pts) with early-stage NSCLC with high risk of relapse and poor prognosis. The aim of this study was to investigate the relationship between the levels of expression of 7 biomarkers, various clinicopathological characteristics and their prognostic significance. Methods Tumor tissue from 82 radically resected stage I-III NSCLC pts were consecutively collected to investigate the mRNA expression and protein levels of the following biomarkers using quantitative reverse transcriptase real-time PCR (qRT-PCR) and immunohistochemistry (IHC) with a tissue microarray technique: excision repair cross-complementation group 1 (ERCC1), breast cancer 1 (BRCA1), ribonucleotide reductase subunit 1 (RRM1), RRM2, p53R2, thymidylate synthase (TS) and class III beta-tubulin (β-Tub-III). Results On a univariate analysis, p53R2 expression was significantly higher in adenocarcinoma (ADK) compared to squamous cell carcinoma (SSC) samples (p = 0.002) and in stage I compared to stage II-III (p ≤ 0.001). ERCC1 expression was significantly higher in females compared to males (p = 0.03), and β-Tub-III expression was significantly higher in ADK than in SSC (p = 0.03). Pts with lower RRM2 expression survived longer than pts with higher RRM2 expression (p = 0.069). The multivariate analysis confirmed RRM2 as an independent prognostic marker of shorter survival (p= 0.031). The comparison between survival curves with qRT-PCR and IHC showed similar results with a trend towards longer survival among ERCC1 negative pts, BRCA1 negative pts, p53R2 positive pts and among pts with low levels of RRM1 and RRM2, although the difference was not statistically significant with both methods. qRT-PCR and IHC have shown that β-Tub-III and TS had no significant impact on survival. Conclusions This is the first study that identifies RRM2 expression as a negative prognostic factor in resected stage I-III NSCLC. Moreover, we have demonstrated the differential expression of p53R2 and β-Tub-III in ADK compared to SSC and higher expression of p53R2 in pts with stage I compared to stage II-III NSCLC. Disclosure All authors have declared no conflicts of interest.