RENAL CELL CARCINOMA MIB-1, BAX AND BCL-2 EXPRESSION AND PROGNOSIS

No AccessJournal of UrologyAdult Urology: Oncology: Renal/Upper Tract/Bladder1 Dec 2004RENAL CELL CARCINOMA MIB-1, BAX AND BCL-2 EXPRESSION AND PROGNOSIS JUKKA P. KALLIO, PASI HIRVIKOSKI, HEIKKI HELIN, TIINA LUUKKAALA, TEUVO L.J. TAMMELA, PIRKKO KELLOKUMPU-LEHTINEN, and PAULA M. MARTIKAINEN JUKKA P. KALLIOJUKKA P. KALLIO More articles by this author , PASI HIRVIKOSKIPASI HIRVIKOSKI More articles by this author , HEIKKI HELINHEIKKI HELIN More articles by this author , TIINA LUUKKAALATIINA LUUKKAALA More articles by this author , TEUVO L.J. TAMMELATEUVO L.J. TAMMELA More articles by this author , PIRKKO KELLOKUMPU-LEHTINENPIRKKO KELLOKUMPU-LEHTINEN More articles by this author , and PAULA M. MARTIKAINENPAULA M. MARTIKAINEN More articles by this author View All Author Informationhttps://doi.org/10.1097/01.ju.0000144334.97639.bfAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Proliferation and programmed cell death (apoptosis) are key factors in oncogenesis and tumor progression. In carcinogenesis important regulators of apoptosis are members of the Bcl-2 family. In this family the Bcl-2 gene has an inhibitory effect on apoptosis, while Bax promotes cell death. In renal cell carcinoma (RCC) the associations between Bcl-2 proteins and RCC prognosis have been controversial. We evaluated Bax and Bcl-2 levels in RCC, and their associations with prognosis, proliferation and traditional prognostic factors. Materials and Methods: Our prospective study population comprised 138 consecutive patients who underwent radical nephrectomy for RCC. Immunostaining and semiquantitative indices for Ki-67 (MIB-1), Bax and Bcl-2 were estimated. Their associations with prognosis were explored. Results: On univariate analysis according to survival statistically significant differences were achieved by Bax (positive vs negative HR 3.04, 95% CI 1.27 to 7.23), Bcl-2 (positive vs negative HR 0.43, 95% CI 0.23 to 0.81), MIB-1 (continuous HR 1.03, 95% CI 1.001 to 1.064), Fuhrman nuclear class (4 vs 1 plus 2 HR 8.15, 95% CI 3.13 to 21.20) and stage (4 vs 1 HR 60.04, 95% CI 13.99 to 257.68). Only stage (HR 47.96, 95% CI 10.85 to 212.03) and Fuhrman classification (HR 4.32, 95% CI 1.60 to 11.65) attained statistical significance on Cox regression multivariate analysis. Conclusions: In our prospective study Bax and Bcl-2 showed a statistically significant association with prognosis in RCC but did not achieve the status of independent prognostic factors. Further studies are needed to clarify the role of the apoptotic process in tumor progression and prognosis. References 1 : The role of the Bcl-2 family in the regulation of outer mitochondrial membrane permeability. Cell Death Differ2000; 7: 1182. Google Scholar 2 : Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature1990; 348: 334. Google Scholar 3 : Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell1995; 80: 293. Google Scholar 4 : Multiple Bcl-2 family members demonstrate selective dimerizations with Bax. Proc Natl Acad Sci USA1995; 92: 7834. Google Scholar 5 : P53, bcl-2, and Bax expression in renal cell carcinoma. Urology1998; 51: 1057. Google Scholar 6 : Expression of bcl-2 oncoprotein in renal cell tumours. J Pathol1995; 177: 247. Google Scholar 7 : Expression of tumour-suppressor gene Rb, apoptosis-suppressing protein Bcl-2 and c-Myc have no independent prognostic value in renal adenocarcinoma. Br J Cancer1995; 71: 863. Google Scholar 8 : Possible significance of VLA-4 (alpha 4 beta 1) for hematogenous metastasis of renal-cell cancer. Int J Cancer1995; 60: 753. Google Scholar 9 : Expression of p53 and bcl-2 in primary locally confined renal cell carcinomas: no evidence for prognostic significance. Anticancer Res1996; 16: 3807. Google Scholar 10 : Expression of genes involved in chemoresistance, proliferation and apoptosis in clinical samples of renal cell carcinoma and correlation with clinical outcome. Anticancer Res2002; 22: 121. Google Scholar 11 : Membranous location of EGFR immunostaining is associated with good prognosis in renal cell carcinoma. Br J Cancer2003; 89: 1266. Google Scholar 12 : Histone mRNA in-situ hybridization in astrocytomas: a comparison with PCNA, MIB-1 and mitoses in paraffin-embedded material. Histopathology1998; 32: 43. Google Scholar 13 : The Heidelberg classification of renal cell tumours. J Pathol1997; 183: 131. Google Scholar 14 : Prognostic significance of morphologic parameters in renal cell carcinoma. Am J Surg Pathol1982; 6: 655. Google Scholar 15 : Apoptosis of renal cell carcinoma and apoptotic related genes bcl-2 and bax. Zhonghua Wai Ke Za Zhi1998; 36: 373. Google Scholar 16 : Apoptosis suppressing protein bcl-2 is expressed in well-differentiated breast carcinomas with favourable prognosis. J Pathol1995; 177: 49. Google Scholar 17 : Enhanced apoptosis predicts shortened survival in non-small cell lung carcinoma. Cancer Res1995; 55: 5595. Google Scholar 18 : Apoptosis and expression of Bcl-2, Bcl-XL, and Bax in renal cell carcinomas. Cancer Invest2002; 20: 324. Google Scholar 19 : The von Hippel-Lindau gene product inhibits renal cell apoptosis via Bcl-2-dependent pathways. J Biol Chem2001; 276: 40599. Google Scholar 20 : Relationship between expression of Bcl-2 genes and growth factors in ischemic acute renal failure in the rat. J Am Soc Nephrol2000; 11: 454. Google Scholar From the Departments of Urology (JPK, TLJT), Pathology (HH, PMM) and Oncology (PK-L) and Research Unit (TL), Tampere University Hospital and Schools of Public Health (TL) and Medicine (TLJT, PK-L), University of Tampere, Tampere and Department of Pathology, Oulu University Hospital (PH), Oulu, Finland© 2004 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited byHirata H, Hinoda Y, Nakajima K, Kikuno N, Suehiro Y, Tabatabai Z, Ishii N and Dahiya R (2018) The bcl2 −938CC Genotype Has Poor Prognosis and Lower Survival in Renal CancerJournal of Urology, VOL. 182, NO. 2, (721-727), Online publication date: 1-Aug-2009. Volume 172Issue 6 Part 1December 2004Page: 2158-2161 Advertisement Copyright & Permissions© 2004 by American Urological Association, Inc.Keywordskidneyapoptosisgene expressioncarcinoma, renal cellprognosisMetricsAuthor Information JUKKA P. KALLIO More articles by this author PASI HIRVIKOSKI More articles by this author HEIKKI HELIN More articles by this author TIINA LUUKKAALA More articles by this author TEUVO L.J. TAMMELA More articles by this author PIRKKO KELLOKUMPU-LEHTINEN More articles by this author PAULA M. MARTIKAINEN More articles by this author Expand All Advertisement PDF downloadLoading ...