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Minichromosome Maintenance Protein 2 Expression in Prostate

Characterization and Association with Outcome after Therapy for Cancer¹

Departments of Urology [M. V. M., G. D. G., P. R. C.] and Pathology [T. W. M., T. D. T.], School of Medicine, and Comprehensive Cancer Center [G. D. G., V. W., P. R. C., T. D. T.], University of California San Francisco, San Francisco, California 94143-0506; Wellcome/CRC Institute [K. S.], and Departments of Pathology [G. H. W., K. S.] and Zoology [K. S.], University of Cambridge, Cambridge CB2 1QP, United Kingdom; and Royal Postgraduate Medical School, Hammersmith Hospital, London W12 0NN, United Kingdom [S. D.]

The minichromosome maintenance (MCM) proteins are highly conserved proteins essential for initiating and regulating eukaryotic DNA replication. Recent studies have demonstrated the potential use of MCM proteins as markers of proliferation. We characterized the pattern of Mcm 2 staining in benign and malignant prostate tissues and examined the role of Mcm 2 expression in disease-free survival after surgery in men with localized prostate cancer.

Tumors from 92 patients who underwent radical prostatectomy for prostate cancer (median follow-up of 54 months) were examined for Mcm 2 expression by immunohistochemistry using a monoclonal antibody. Prostate tissue from five men without histopathological evidence of prostate cancer was also stained for Mcm 2. Mcm 2 expression was quantified by calculating a labeling index, and patients were grouped according to degree of staining. An analysis of the association between Mcm 2 expression with traditional clinicopathological characteristics of prostate cancer was carried out. A Cox proportional hazards analysis was performed to determine whether Mcm 2 staining was a significant independent predictor of disease-free survival.

Mcm 2 expression is low (<2%) and limited to the basal cell layer in nonmalignant prostate glands. Mcm 2 expression is consistently increased in malignant glands and is significantly associated with disease-free survival in univariate (P = 0.002) and multivariate (P = 0.01) analyses. Patients with high Mcm 2 expression exhibited shorter disease-free survival. Mcm 2 expression was not associated with any traditional clinical or pathological factors and therefore is an independent predictor of survival in these patients with prostate cancer.

These data support evidence that Mcm 2 may serve as a novel proliferation marker in the prostate. Mcm 2 expression is an independent predictor of disease-free survival after definitive local therapy and has potential as a molecular marker for clinical outcome in prostate cancer.

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