Research Article Expression of Ribonucleotide Reductase Subunit-2 and Thymidylate Synthase Correlates with Poor Prognosis in Patients with Resected Stages I–III Non-Small Cell Lung Cancer Francesco Grossi, 1 Maria Giovanna Dal Bello, 1 Sandra Salvi, 2 Roberto Puzone, 3 Ulrich Pfeffer, 4 Vincenzo Fontana, 5 Angela Alama, 1 Erika Rijavec, 1 Giulia Barletta, 1 Carlo Genova, 1 Claudio Sini, 1 Giovanni Battista Ratto, 6 Mario Taviani, 6 Mauro Truini, 2 and Domenico Franco Merlo 5 1 Lung Cancer Unit, IRCCS A.O.U San Martino IST-Istituto Nazionale per la Ricerca sul Cancro, Largo Rosanna Benzi 10, 16132 Genova, Italy 2 Pathology and Cytohistology Division, IRCCS A.O.U San Martino IST-Istituto Nazionale per la Ricerca sul Cancro, Largo Rosanna Benzi 10, 16132 Genova, Italy 3 Clinical Epidemiology Division, IRCCS A.O.U San Martino IST-Istituto Nazionale per la Ricerca sul Cancro, Largo Rosanna Benzi 10, 16132 Genova, Italy 4 Integrated Molecular Pathology Division, IRCCS A.O.U San Martino IST-Istituto Nazionale per la Ricerca sul Cancro, Largo Rosanna Benzi 10, 16132 Genova, Italy 5 Epidemiology, Biostatistics and Clinical Trials Division, IRCCS A.O.U San Martino IST-Istituto Nazionale per la Ricerca sul Cancro, Largo Rosanna Benzi 10, 16132 Genova, Italy 6 Toracic Surgery Division, IRCCS A.O.U San Martino IST-Istituto Nazionale per la Ricerca sul Cancro, Largo Rosanna Benzi 10, 16132 Genova, Italy Correspondence should be addressed to Francesco Grossi; francesco.grossi@hsanmartino.it Received 10 August 2015; Revised 5 October 2015; Accepted 7 October 2015 Academic Editor: Robert Pichler Copyright © 2015 Francesco Grossi et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Biomarkers can help to identify patients with early-stages or locally advanced non-small cell lung cancer (NSCLC) who have high risk of relapse and poor prognosis. To correlate the expression of seven biomarkers involved in DNA synthesis and repair and in cell division with clinical outcome, we consecutively collected 82 tumour tissues from radically resected NSCLC patients. Te following biomarkers were investigated using IHC and qRT-PCR: excision repair cross-complementation group 1 (ERCC1), breast cancer 1 (BRCA1), ribonucleotide reductase subunits M1 and M2 (RRM1 and RRM2), subunit p53R2, thymidylate synthase (TS), and class III beta-tubulin (TUBB3). Gene expression levels were also validated in an available NSCLC microarray dataset. Multivariate analysis identifed the protein overexpression of RRM2 and TS as independent prognostic factors of shorter overall survival (OS). Kaplan- Meier analysis showed a trend in shorter OS for patients with RRM2, TS, and ERCC1, BRCA1 overexpressed tumours. For all of the biomarkers except TUBB3, the OS trends relative to the gene expression levels were in agreement with those relative to the protein expression levels. Te NSCLC microarray dataset showed RRM2 and TS as biomarkers signifcantly associated with OS. Tis study suggests that high expression levels of RRM2 and TS might be negative prognostic factors for resected NSCLC patients. 1. Introduction Only 30–40% of new patients diagnosed with NSCLC have disease confned to the thorax. Te standard of care for patients with early-stage NSCLC is surgical resection, but 50– 60% of patients with local disease relapse within two years [1]. Te 5-year overall survival (OS) by pathologic stage is, respectively, 73% and 54% for stages IA and IB, 48% and Hindawi Publishing Corporation Disease Markers Volume 2015, Article ID 302649, 18 pages http://dx.doi.org/10.1155/2015/302649