title: Lower expression levels of the transforming growth factor beta receptor type II protein are associated with a less aggressive tumor phenotype and improved survival among patients with clear cell renal cell carcinoma.
abstract: Loss of expression of the transforming growth factor beta type II receptor (TbetaRII) has been implicated as an important event in renal carcinogenesis; however, its role as a potential prognostic factor remains poorly understood. Using archived tumor samples and long-term follow-up on a cohort of 280 clear cell renal cell carcinoma (ccRCC) patients treated with surgery from 1980 to 1998, we evaluated the association of TbetaRII expression and cancer-specific survival in both a univariate and multivariate setting. Low tumor expression of TbetaRII is associated with a less aggressive tumor phenotype at time of surgery. Moreover, those patients with lower levels of TbetaRII expression experience better cancer-specific survival than patients with higher levels of TbetaRII expression (log rank P = .034). Based on a Cox proportional hazard model adjusting for age, patients with tumors showing low (hazard ratio, 0.49; 95% confidence interval, 0.27-0.88) and moderate (hazard ratio, 0.7; 95% confidence interval, 0.40-1.23) TbetaRII expression are at decreased risk of RCC death compared with patients with tumors having high levels of TbetaRII expression. Adjustment for well-known pathologic predictors of RCC outcome attenuates the association of TbetaRII expression and ccRCC survival. Of interest, the association with TbetaRII expression appears more pronounced among those patients with tumors showing less aggressive phenotypes. Data from this investigation are the first to suggest that loss of TbetaRII expression is associated with improved ccRCC patient survival, especially among those patients with less aggressive disease profiles at time of surgery.
authors.affiliation: Department of Urology, Mayo Clinic, Jacksonville, FL 32224, USA. parker.alexander@mayo.edu
authors.forename: Alexander Scott
authors.initials: AS
authors.lastname: Parker
authors.forename: Christine M
authors.initials: CM
authors.lastname: Lohse
authors.forename: Kevin
authors.initials: K
authors.lastname: Wu
authors.forename: Pamela
authors.initials: P
authors.lastname: Kreinest
authors.forename: John A
authors.initials: JA
authors.lastname: Copland
authors.forename: Tracy
authors.initials: T
authors.lastname: Hilton
authors.forename: Michael
authors.initials: M
authors.lastname: Wehle
authors.forename: John C
authors.initials: JC
authors.lastname: Cheville
authors.forename: Michael
authors.initials: M
authors.lastname: Blute
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D002292:Carcinoma, Renal Cell / Q000401:mortality / Q000503:physiopathology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000401:mortality / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis*; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D018125:Receptors, Transforming Growth Factor beta