Minichromosome maintenance protein-2 as a diagnostic marker in bladder cancer

Linda Gordon, Keith Stewart, Mary McKean

Research output: Contribution to specialist publicationFeatured article

Abstract

Minichromosome Maintenance Proteins (MCMs) are important regulators of the cell cycle and highly specific for cell proliferation. They have been identified as potential tumour markers in cervical and colorectal cancers. The aim of this study was to investigate MCM-2 as a predictive marker of bladder cancer progression and as a marker of malignant cells in liquid based cytology (LBC) urine samples.

Three tissue microarrays (TMAs) were constructed: - single event/no recurrence pTa-T1 (32 patients); recurrent/non-progressive pTa-T1 (21 patients); and recurrent/progressing to muscle invasive disease pTa-T1 - T2-T4 (21 patients). The TMAs were stained with a monoclonal antibody to the MCM-2 protein and scored on a scale of 0- 4.
MCM-2 levels were determined in LBC urine samples from 56 patients who had a diagnosis of bladder cancer as determined by cystoscopy. These were compared to standard cytology and histopathology.

The mean staining scores for MCM-2 expression for progressive, recurrent and single event TMAs were 0.9, 1.1 and 0.9 respectively. In the progressive bladder cancer group MCM-2 levels also increased with disease progression.
The sensitivity of the LBC- MCM-2 test, compared to histopathology was 93%. It also showed agreement with standard urinary cytology in 91% of malignant cases and 13 suspicious/atypical cases were shown to be MCM-2 positive.

These results show that MCM-2 does have the potential to predict the progression of bladder cancer. The ability to detect MCM-2 in bladder cancer cells in urine could lead to the development of a non invasive screening and monitoring test for bladder cancer.

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