title: Ribonucleotide reductase M2 subunit is a novel diagnostic marker and a potential therapeutic target in bladder cancer.
abstract: OBJECTIVE
  To examine the immunohistochemical expression and function of ribonucleotide reductase M2 subunit (RRM2), a gemcitabine-related molecule, in bladder cancer.
  
  
  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.
authors.affiliation: Department of Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan. tmorikawa-tky@umin.ac.jp
authors.forename: Teppei
authors.initials: T
authors.lastname: Morikawa
authors.forename: Daichi
authors.initials: D
authors.lastname: Maeda
authors.forename: Haruki
authors.initials: H
authors.lastname: Kume
authors.forename: Yukio
authors.initials: Y
authors.lastname: Homma
authors.forename: Masashi
authors.initials: M
authors.lastname: Fukayama
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D034741:RNA, Small Interfering; D012262:Ribonucleoside Diphosphate Reductase / Q000235:genetics / Q000378:metabolism*; D046888:Tissue Array Analysis; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism*; D019459:Urothelium / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D034741:RNA, Small Interfering; C093713:ribonucleotide reductase M2; D012262:Ribonucleoside Diphosphate Reductase