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MCM2 Is an Independent Predictor of Survival in Patients With Non–Small-Cell Lung Cancer

From the Lung Cancer Program, Roswell Park Cancer Institute, Buffalo, NY; and Department of Surgery, University of California at Los Angeles, Los Angeles, CA.

Address reprint requests to Gerold Bepler, MD, PhD, Thoracic Oncology Program, Moffitt Cancer Center and Research Institute, MRC-MOLONC, 12902 Magnolia Dr, Tampa, FL 33612; email: beplerg{at}moffitt.usf.edu

PURPOSE: Minichromosome maintenance protein 2 (MCM2) is a component of the prereplicative complex. It is essential for eukaryotic DNA replication and is only expressed in proliferating cells. The prognostic utility of MCM2 compared with Ki-67, another marker of proliferating cells, on survival of patients with non–small-cell lung cancer (NSCLC) was studied.

PATIENTS AND METHODS: We examined the immunohistochemical expression of MCM2 and Ki-67 in primary pathologic tumor specimens from 221 NSCLC patients. For each marker, the fraction of tumor cells with positive staining was assessed as a percentage and categorized into four groups: 0% to 24%, 25% to 49%, 50% to 74%, and 75%. MCM2 and Ki-67 immunoreactivities were compared with each other, and associations with pathologic and clinical parameters predictive of survival were analyzed with the ² test. Cox regression models were used to assess associations between MCM2 and Ki-67 and survival while controlling for confounders.

RESULTS: Independent variables significantly associated with survival were tumor stage, performance status, and staining category. Patients with less than 25% MCM2 immunoreactivity had a longer median survival time than patients with 25% MCM2 immunoreactivity (46 v 31 months; P = .039) and a lower relative risk (RR) of death (RR, 0.55, 95% confidence interval, 0.34 to 0.88). There was no significant association between survival and Ki-67 expression.

CONCLUSION: Immunostaining of tumor cells for MCM2 is an independent prognostic parameter of survival for patients with NSCLC. Interpretable results can be obtained on more than 96% of paraffin-embedded specimens, and approximately 35% will be in the favorable subgroup, with less than 25% positively stained tumor cells. Whether MCM2 is predictive of response to therapy needs to be studied.

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