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Histopathology. 2010 Dec;57(6):885-92. doi: 10.1111/j.1365-2559.2010.03725.x.

Ribonucleotide reductase M2 subunit is a novel diagnostic marker and a potential therapeutic target in bladder cancer.

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1
Department of Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan. tmorikawa-tky@umin.ac.jp

Abstract

AIMS:

To examine the immunohistochemical expression and function of ribonucleotide reductase M2 subunit (RRM2), a gemcitabine-related molecule, in bladder cancer.

METHODS AND RESULTS:

One hundred and seventeen bladder specimens on a tissue microarray were immunostained for RRM2. Positive RRM2 staining was observed in none of 14 examples of non-neoplastic urothelium, none of four low-grade urothelial carcinoma (UC), 69 of 83 (83%) high-grade UC, three of three (100%) squamous cell carcinoma and 12 of 13 (92%) lymph node metastasis of UC. RRM2 overexpression was associated significantly with muscularis propria invasion in UC patients who had undergone radical cystectomy (P=0.005). Immunohistochemistry for RRM2 was then applied to small biopsy specimens of 15 cystitis with reactive atypia cases and 25 urothelial carcinoma in-situ (CIS) cases. Positive RRM2 staining was found in one of 15 (6.7%) cystitis with reactive atypia cases and in 24 of 25 (96%) CIS cases. Finally, UM-UC-3 bladder cancer cells were transfected with RRM2 siRNAs and cell growth was evaluated. Knockdown of RRM2 protein markedly inhibited cell growth.

CONCLUSIONS:

We have shown frequent overexpression of RRM2 protein and its possible role in bladder cancer. Our results suggest that RRM2 is a novel diagnostic marker and a potential therapeutic target in bladder cancer.

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