ORIGINAL ARTICLE

DNA replication regulation protein Mcm7 as a marker of proliferation in prostate cancer

V Padmanabhan¹, P Callas², G Philips³, T D Trainer¹ and B G Beatty¹

¹ Department of Pathology, University of Vermont, Burlington, VT 05405, USA
² Department of Biostatistics, University of Vermont
³ Department of Medicine, University of Vermont

Correspondence to:
Correspondence to:
Professor T D Trainer
Department of Pathology, University of Vermont, College of Medicine, Burlington, VT 05405, USA; thomas.trainer{at}vtmednet.org

Background: Recent studies have shown that minichromosome maintenance (MCM) proteins (Mcm2–7) may be useful proliferation markers in dysplasia and cancer in various tissues.

Aims: To investigate the use of Mcm7 as a proliferation marker in 79 lymph node negative prostate cancers and compare it with Ki-67, a commonly used cell proliferation marker.

Methods: The percentage of proliferating cells (proliferation index; PI) was calculated for basal and luminal epithelial cells in benign prostate tissue, prostatic intraepithelial neoplasia (PIN), and epithelial cells in adenocarcinoma. The PI for each biomarker was correlated with the preoperative prostate specific antigen concentration, the Gleason score, surgical resection margin status, and the AJCC pT stage for each patient.

Results: The mean PIs for Ki-67 and Mcm7 were: benign luminal epithelium 0.7 and 1.2 and benign basal epithelium 0.8 and 8.2; PIN non-basal epithelium 4.9 and 10.6 and PIN basal epithelium 0.7 and 3.1; adenocarcinoma 9.8 and 22.7, respectively. Mcm7 had a significantly higher mean PI (p<0.0001) than Ki-67 for all cell categories except benign luminal epithelial cells. Mcm7 was a better discriminatory marker of proliferation between benign epithelium, PIN, and invasive adenocarcinoma (p<0.0001) than Ki-67. The drop in Mcm7 mean basal cell PI from benign epithelium to PIN epithelium was significantly larger than for Ki-67 (p<0.0001). Mcm7 had a significantly higher PI than Ki-67 at each risk level.

Conclusion: Mcm7 may be a useful proliferation marker in prostatic neoplasia and warrants further evaluation as a complementary tool in the diagnosis of PIN and prostate carcinoma.

Abbreviations: H&E, haematoxylin and eosin; MCM, minichromosome maintenance; PCNA, proliferating cell nuclear antigen; PI, proliferation index; PIN, prostatic intraepithelial neoplasia; PSA, prostate specific antigen

Keywords: prostate cancer; high grade prostatic intraepithelial neoplasia; cell proliferation; proliferation index; Mcm7; Ki-67

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