Conventional (clear cell) renal carcinoma metastases have greater bcl-2 expression than high-risk primary tumors Journal Article


Authors: Lee, C. T.; Genega, E. M.; Hutchinson, B.; Fearn, P. A.; Kattan, M. W.; Russo, P.; Reuter, V. E.
Article 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 (pT3) primary tumors and in matched patient metastases. Immunohistochemical analysis of bcl-2 was performed on 149 cases of conventional (clear cell) RCC (112 pT3 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. © 2003 Elsevier Inc. All rights reserved.
Keywords: immunohistochemistry; adult; cancer survival; aged; aged, 80 and over; disease-free survival; middle aged; survival analysis; retrospective studies; major clinical study; protein bcl 2; metastasis; apoptosis; cohort studies; neoplasm recurrence, local; gene expression; neoplasm proteins; protein bcl xl; protein p53; kidney carcinoma; kidney neoplasms; nephrectomy; cancer resistance; cancer center; gene expression regulation, neoplastic; statistical analysis; carcinoma, renal cell; tumor recurrence; clear cell carcinoma; metastases; proto-oncogene proteins c-bcl-2; bcl-2; genes, bcl-2; humans; prognosis; human; male; female; priority journal; article; renal neoplasm
Journal Title: Seminars in Urologic Oncology
Volume: 21
Issue: 3
ISSN: 1081-0943
Publisher: W.B. Saunders Co.  
Date Published: 2003-05-01
Start Page: 179
End Page: 184
Language: English
PUBMED: 12810203
PROVIDER: scopus
DOI: 10.1016/S1078-1439(02)00236-3
DOI/URL:
Notes: Export Date: 12 September 2014 -- Source: Scopus
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MSK Authors
  1. Paul Russo
    569 Russo
  2. Victor Reuter
    1199 Reuter
  3. Paul A Fearn
    58 Fearn
  4. Michael W Kattan
    218 Kattan