Using tumor markers to predict the survival of patients with metastatic renal cell carcinoma

Department of Urologic Oncology, Roswell Park Cancer Institute, Buffalo, New York, USA.
The Journal of Urology (Impact Factor: 3.75). 05/2005; 173(5):1496-501. DOI: 10.1097/01.ju.0000154351.37249.f0
Source: PubMed

ABSTRACT Approximately 30% of renal cell carcinomas (RCCs) present as metastatic disease. Molecular markers have the potential to characterize accurately the biological behavior of tumors and they may be useful for determining prognosis.
A custom tissue array was constructed using clear cell RCC from 150 patients with metastatic RCC who underwent nephrectomy prior to immunotherapy. The tissue array was stained for 8 molecular markers, namely Ki67, p53, gelsolin, carbonic anhydrase (CA)9, CA12, PTEN (phosphatase and tensin homologue deleted on chromosome 10), epithelial cell adhesion molecule and vimentin. Marker status and established clinical predictors of prognosis were considered when developing a prognostic model for disease specific survival.
On univariate Cox regression analysis certain markers were statistically significant predictors of survival, namely CA9 (p <0.00001), p53 (p = 0.0072), gelsolin (p = 0.030), Ki67 (p = 0.036) and CA12 (p = 0.043). On multivariate Cox regression analysis that included all markers and clinical variables CA9 (p = 0.00002), PTEN (p <0.0001), vimentin (p = 0.0032), p53 (p = 0.028), T category (p = 0.0025) and performance status (p = 0.0013) were significant independent predictors of disease specific survival and they were used to construct a combined molecular and clinical prognostic model. The bias corrected concordance index (C-index) of this combined prognostic model was C = 0.68, which was significantly higher (p = 0.0033) than that of a multivariate clinical predictor model (C = 0.62) based on the UCLA Integrated Staging System (T category, histological grade and performance status).
In patients with clear cell RCC a prognostic model for survival that includes molecular and clinical predictors is significantly more accurate than a standard clinical model using the combination of stage, histological grade and performance status.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: The aim of this study was to investigate the expression of p21 and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in renal cell carcinoma (RCC) and to evaluate their correlation with clinicopathological variables. Materials and methods: Using immunohistochemistry, we studied the expression of p21 and PTEN in a tissue microarray of 50 cases of RCC, including different histological subtypes. Marker expression was correlated to clinicopathological variables. Results: p21 nuclear immunostaining was observed in 72% of cases. Higher p21 expression was significantly associated with higher stage RCCs (P=0.022) and with worse patient outcome (P=0.050). Higher expression of p21 was observed in metastatic RCC and in RCC with venous invasion; however, this relation was not statistically significant (P=0.330 and 0.414, respectively). PTEN was expressed in 80% of cases. Papillary RCC showed a significantly higher expression of PTEN compared with clear cell RCC (P=0.003). There was an inverse correlation between the levels of expression of p21 and PTEN, but this was not statistically significant (P=0.095). Conclusion: Assessment of p21 and PTEN expression in RCC may aid prediction of the biologic behavior of the tumor and identification of the appropriate candidates for targeted therapy. Higher p21 expression could be considered a poor prognostic factor for RCC. Papillary RCC show higher PTEN expression compared with clear cell RCC, and thus may less likely benefit from the mammalian target of rapamycin inhibitor therapy.
    07/2013; 33(1):66-75. DOI:10.1097/01.XEJ.0000429926.01489.93
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Carbonic anhydrase IX (CAIX) protein has been correlated with progression and survival in patients with renal cell carcinoma (RCC). The prognostic value of CAIX in RCC however, remains inconclusive according to published works. This study aimed to analyze CAIX as a biological marker to predict RCC patient prognosis. A literature search of the PubMed and Web of Knowledge databases was performed to retrieve original studies from their inception to December of 2013. Fifteen studies, collectively including a total of 2611 patients with renal cell carcinoma, were carefully reviewed. Standard meta-analysis methods were applied to evaluate the prognostic impact of CAIX expression on patient prognosis. The hazard ratio (HR) and its 95% confidence interval (CI) were recorded for the relationship between CAIX expression and survival, and the data were analyzed using Review Manager 5.2 software and Stata software 11.0. In patients with RCC, low CAIX expression was associated with poor disease-specific survival (HR = 1.89, 95% CI: 1.20-2.98, P = 0.006), unfavorable progression-free survival (HR = 2.62, 95% CI: 1.14-6.05, P = 0.02) and worse overall survival (HR = 2.03, 95% CI: 1.28-3.21, P = 0.002). Furthermore, low CAIX expression was significantly associated with the presence of lymph node metastases (odds ratio (OR) = 0.31, 95% CI = 0.15-0.62, P = 0.0009) and distant metastases (OR = 0.66, 95% CI = 0.46-0.96, P = 0.03) and predicted a higher tumor grade (OR = 0.41, 95% CI = 0.31-0.54, P<0.00001). Low CAIX expression most likely indicates poor prognosis in RCC patients. Moreover, low CAIX expression was significantly associated with unfavorable clinicopathological factors. To strengthen our findings, further well-designed prospective studies should be conducted to investigate the role of CAIX expression in RCC.
    PLoS ONE 11/2014; 9(11):e114096. DOI:10.1371/journal.pone.0114096 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Zinc is an indispensable trace element which is vital for the functioning of numerous cellular processes like cell replication and growth. Cellular zinc homeostasis is tightly regulated by zinc transporters involved in zinc influx and efflux processes. Notwithstanding, the association of zinc transporters with the aggressiveness of cancer, especially renal cell carcinoma (RCC), is unknown. In view of the fact, the present study was initiated to ascertain whether ZIP10 transporter expression is modulated during RCC progression. A total of 57 samples of RCC and corresponding normal renal tissue were analyzed for ZIP10 gene expression by real time PCR. We observed significantly higher expression of ZIP10 mRNA (P=0.002) in high grades clear cell RCC tissue (Grade III, IV) as compared to low grades clear cell RCC tissue (Grade I & II). A significant difference was also observed in the ZIP10 expression in different types of RCC (P=0.001). This is the first study which shows a significant correlation between ZIP10 mRNA expression with aggressiveness of RCC. Therefore, ZIP10 mRNA expression could be used as a possible biomarker for the aggressive behavior of RCC and a promising target of novel treatment strategies.
    Gene 09/2014; 552(1). DOI:10.1016/j.gene.2014.09.010 · 2.08 Impact Factor