240 - Mcm as a useful biomarker for graded differentiation in urothelial cancer

Date 28 September 2012
Event ESMO Congress 2012
Session Publication Only
Topics Urothelial Cancers
Translational Research
Presenter Nadira Narine
Authors N. Narine1, D.N. Rana2, G.D. Stewart3, B.M. Thottakam4, A. Donnini5, A. Wilson6, B. Turner7, W. Burrill8, K. Saeb-Parsy9, D. Harrison10
  • 1Cytology Department, Csb2, Central Manchester Hospitals NHS Foundation, M13 9WL - Manchester/UK
  • 2Cytology Department, Central Manchester Hospitals NHS Foundation, M13 9WL - Manchester/UK
  • 3Department Of Urology And Edinburgh Urological Cancer Group, Western General Hospital, EH16 4SA - Edinburgh/UK
  • 4Cytosystems Ltd, AB21 9TR - ABERDEEN/UK
  • 5Research And Development, Cytosystems Ltd, AB21 9TR - ABERDEEN/UK
  • 6Department Of Computing, Robert Gordon University, AB10 1FR - Aberdeen/UK
  • 7Department Of Urology, Homerton University Hospital NHS Foundation Trust, E9 6SR - London/UK
  • 8University Of Bradford, Ethical Tissue, BD7 1DP - Bradford/UK
  • 9Department Of Urology, Addenbrooke's Hospital, CB2 0QQ - Cambridge/UK
  • 10Director Of Laboratory Medicine, Nhs Lothian, Royal Infirmary of Edinburgh, EH16 4SA - Edinburgh/UK

Abstract

Introduction

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
G1 3 3207 5026 600
G2 9 8177 15975 3000
G3 13 14795 14167 10000
CIS 1 40000 - 40000
Total 26

Conclusion

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.