240 - Mcm as a useful biomarker for graded differentiation in urothelial cancer
|Date||28 September 2012|
|Event||ESMO Congress 2012|
|Topics|| Urothelial Cancers
N. Narine1, D.N. Rana2, G.D. Stewart3, B.M. Thottakam4, A. Donnini5, A. Wilson6, B. Turner7, W. Burrill8, K. Saeb-Parsy9, D. Harrison10
Urine cytology has been used in the diagnosis of urothelial cancer (UC) for high grade and in-situ lesions. Sensitivity for low grade carcinoma is problematic leading to both over and under diagnoses. To reduce this dilemma a number of biomarkers have been tried with varying results. Minichromsome Maintenance Proteins (MCMs) play a regulatory role in eukaryotic DNA replication and are expressed as normal cells progress from G0 into G1/S phase of the cell cycle. Over expression has been demonstrated in neoplasia in many sites including urothelium. The aim of the study was to evaluate use of MCM2 in urine cytology and tissue specimens to differentiate high grade from low grade UC.Methods
epithelial cells retrieved from urine samples of 114 patients were stained with MCM2 using an immunocytochemical technique. MCM2 was similarly applied to 13 archived urothelial tumour specimens. MCM positive cell counts were performed on all cytology specimens and results correlated to the different grades of UC. Tumor specimens were evaluated for MCM2 staining intensity, distribution and percentage of positive cells.Results
26 of 114 patients were found to have UC. In cytology specimens the MCM mean and median cell counts increased with grade of cancer (Table 1). Non cancerous urines had mean and median MCMs of 232 and 14 respectively. In urothelial solid tissue tumour specimens, MCM2 showed strong nuclear staining characteristics where the percentage of positive cells was related to tumor grade. The lowest percentage MCM stained cells was noted in grade 1 tumours, the highest percentage in grade 3. Staining distribution was predominantly in the basal zone of the urothelium in grade 1 tumours, basal and middle epithelial zones in grade 2, and more diffusely distributed in grade 3 tumours. Table 1: MCM cell count with increasing grade of urothelial cancer.
|Grade||Number of cases||Mean||Standard Deviation||Median|
MCM2 could be a useful biomarker in differentiating low grade from high grade UC both in cytology and biopsy tissue specimens.Disclosure
All authors have declared no conflicts of interest.