Minichromosomal maintenance proteins (MCM’s) as biomarkers for prostate cancer

Proc Amer Assoc Cancer Res, Volume 46, 2005 3163 Introduction: Prostate cancer is the most frequently occurring cancer in men accounting for 33% of cancer incidence and 10% of cancer deaths (American Cancer Society, 2004). Current diagnosis includes measurement of Prostate Specific Antigen (PSA) and digital rectal examination. These techniques provide valuable information, but are questionable with respect to sensitivity and specificity, especially since data reveals that PSA is not prostate specific and a variety of factors can alter its levels. This study aims to investigate MCMs (Mini-chromosomal maintenance proteins), as alternative markers of prostate disease. MCMs function in the ‘licensing’ of replication. Therefore, expression of these molecules is believed to increase in dysplastic and neoplastic cells. Recent work reveals that there is increased expression of MCM5 in the urine sediment of patients with bladder and prostate cancer, and that increased expression of MCM5 in tissue sections is predictive of bladder and colon cancer. Materials and Methods: Ethical approval was obtained from Northamptonshire Local Research Ethics Committee and informed consent was sought from patients undergoing investigation for prostate disease. Biopsy tissue was fixed in formalin and embedded in paraffin. Sections from 41 patients, representing the spectrum of benign and malignant disease, were examined following microwave antigen retrieval (0.01M sodium citrate buffer, pH 6.0) using immunohistochemistry with antibodies against MCM-2, -5 and -7 (Stratech, Cambridge UK). Results: This preliminary study reveals that MCM-2 and -7 proteins show little expression in non-involved or benign tissue, yet both are expressed in malignant tissue and appear to intensify as the grade and stage increases. MCM-5, like MCM-2 and -7, is hardly expressed in non-involved tissue but is expressed both in benign and malignant tissue, in which expression increases with both stage and grade. Although the localisation of staining is generally nuclear, in malignant cases cytoplasmic staining, which appears to increase with stage and grade, is also noted especially in the case of MCM-5. Discussion: There is an increasing body of evidence that MCM expression may be a valuable tool for assessing cancer. This study suggests that MCM -2, -5 and -7 are increasingly expressed correlating with the severity of prostate disease. Further analysis needs to be performed to conclude whether MCM proteins may contribute valuable information to current diagnostic strategy, and whether these molecules have potential for use in some type of non-invasive technique.