title: Conventional (clear cell) renal carcinoma metastases have greater bcl-2 expression than high-risk primary tumors.
abstract: Bcl-2 antagonizes p53-induced apoptosis and may contribute to chemoresistance. In renal cell carcinoma (RCC), the role of bcl-2 is not well-defined, though its expression is reportedly low in primary tumors and lacks prognostic value. This study evaluates patterns of bcl-2 expression in high-risk (pT(3)) primary tumors and in matched patient metastases. Immunohistochemical analysis of bcl-2 was performed on 149 cases of conventional (clear cell) RCC (112 pT(3) primaries, 37 metastases). Paraffin-embedded tissues were obtained from nephrectomies and metastatic resections. Median follow up was 48 months in the entire cohort and 69 months in living patients. We evaluated associations between bcl-2 expression and tumor recurrence or patient survival with the Cox regression test, and used the t-test and Pearson correlation methods to evaluate bcl-2 expression in primary and metastatic cases. Bcl-2 expression was observed at a higher frequency in metastases (21/37 cases; 57%) compared to primary tumors (24/112 cases; 21%; P < 0.001). The percentage of cells stained was greater in metastases than primary tumors (P = 0.003). This finding was also noted when expression in metastatic cases was compared with matched primaries (P = 0.05). Bcl-2 expression did not predict disease-free (P = 0.30), disease-specific (P = 0.90), or overall (P = 0.51) survival. Most RCC primary tumors have low-to-absent levels of bcl-2 protein, whereas most RCC metastases display greater protein levels. Bcl-2 expression in primary tumors does not predict clinical outcome. However, expression of bcl-2 protein occurs at a high frequency in RCC metastases when compared to primary tumors. It may be reasonable to target RCC patients displaying altered bcl-2 levels for molecular therapies, such as anti-bcl2, should metastatic disease develop.
authors.affiliation: Department of Urology, University of Michigan, 1500 E. Medical Center Drive, Box 0330, Ann Arbor, MI 49109, USA. ctlee@umich.edu
authors.forename: Cheryl T
authors.initials: CT
authors.lastname: Lee
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Genega
authors.forename: Brian
authors.initials: B
authors.lastname: Hutchinson
authors.forename: Paul A
authors.initials: PA
authors.lastname: Fearn
authors.forename: Michael W
authors.initials: MW
authors.lastname: Kattan
authors.forename: Paul
authors.initials: P
authors.lastname: Russo
authors.forename: Victor E
authors.initials: VE
authors.lastname: Reuter
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000556:secondary* / Q000601:surgery; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019254:Genes, bcl-2; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009364:Neoplasm Recurrence, Local; D009392:Nephrectomy; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2