Using Tumor Markers to Predict the Survival of Patients With Metastatic Renal Cell Carcinoma

Kim, Hyung L.; Seligson, David B.; Liu, Xueli; Janzen, Nicolette; Bui, Matthew; Hong, Yuling; Shi, Tao; Belldegrun, Arie S.; Horvath, Steve; Figlin, Robert A.

doi:10.1097/01.ju.0000154351.37249.f0

Cited by 201 publications

(132 citation statements)

References 17 publications

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“…However, most of the literature about the utility of CA-IX as a prognostic marker on ccRCC comes from series of patients with metastatic cancer (10)(11)(12), with a lack of series on non-metastatic cancer.…”

Section: Carbonic Anhydrase IX Is Not a Predictor Of Outcomes In Non-mentioning

confidence: 99%

Carbonic Anhydrase IX is Not a Predictor of Outcomes in Non-Metastatic Clear Cell Renal Cell Carcinoma - A Digital Analysis of Tissue Microarray

et al. 2013

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Introduction:The knowledge about the molecular biology of clear cell renal cell carcinoma (ccRCC) is evolving, and Carbonic Anhydrase type IX (CA-IX) has emerged as a potential prognostic marker in this challenging disease. However, most of the literature about CA-IX on ccRCC comes from series on metastatic cancer, with a lack of series on non-metastatic cancer. The objective is to evaluate the expression of CA-IX in a cohort of non-metastatic ccRCC, correlating with 1) overall survival, and 2) with established prognostic parameters (T stage, tumor size, Fuhrman nuclear grade, microvascular invasion and peri-renal fat invasion). Materials and Methods: This is a retrospective cohort study. We evaluated 95 patients with non-metastatic clear cell renal cell carcinoma, as to the expression of CA-IX. The analyzed parameters where: overall survival (OS), TNM stage, tumor size (TS), Fuhrman nuclear grade (FNG), microvascular invasion (MVI), peri-renal fat invasion (PFI). We utilized a custom built tissue microarray, and the immunoexpression was digitally quantified using the Photoshop® software. Results: The mean follow-up time was 7.9 years (range 1.9 to 19.5 years).The analysis of CA-IX expression against the selected prognostic parameters showed no correlation.

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Section: Carbonic Anhydrase IX Is Not a Predictor Of Outcomes In Non-mentioning

confidence: 99%

Carbonic Anhydrase IX is Not a Predictor of Outcomes in Non-Metastatic Clear Cell Renal Cell Carcinoma - A Digital Analysis of Tissue Microarray

et al. 2013

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“…In renal cell cancer, PTEN gene expression has been shown to be downregulated in a large percentage of cases, presumably by epigenetic silencing (Brenner et al, 2002;Velickovic et al, 2002). In particular, lack of PTEN expression has been shown to be an independent negative prognostic factor for diseasespecific survival in patients with metastatic renal cell carcinoma (Kim et al, 2005). However, in culture, most of the renal cancer cell lines remain poorly sensitive to rapalogues.…”

Section: Differential Review Of Biological Effects Of Mtor Inhibitionmentioning

confidence: 99%

mTORC1 inhibitors: is temsirolimus in renal cancer telling us how they really work?

et al. 2008

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The proof of principle that a drug targeting mTOR can improve survival has been obtained recently from a large randomised trial using temsirolimus as a first-line therapy in patients with advanced poor prognostic renal cell carcinoma. Consistent data have recently shown the important role of the PI3K/AKT/mTOR signalling pathway in the regulation of crucial metabolic and mitotic functions of cancer cells and endothelial cells allowing a better understanding of the role of mTOR in controlling cancer cell proliferation and survival as well as tumour angiogenesis. As a result, rapamycin derivatives (rapalogues) that block mTOR/Raptor complex 1 were shown to exert direct antiproliferative effects against endometrial cancers, in which cancer cells frequently lose PTEN function as well as mantle cell lymphomas, in which cancer cell proliferation appears to be driven primarily by cyclin D1 overexpression. The overall antitumour effects of rapalogues in renal cell carcinoma appear to be more complex with tumour growth inhibition resulting from direct G1/S cell cycle blockage and/or apoptotic effects in carcinoma cells along with the inhibition of downstream signalling of the HIF1a-induced VEGF/VEGFR autocrine loop in endothelial cells shutting down the maintenance of tumour angiogenesis. Despite extensive cognitive researches, it is difficult to appraise which of those mechanisms is predominant in patients. This review focuses on mechanisms of action of rapalogues focusing on antitumour effects in patients with renal cell carcinoma.

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“…While tumour biology clearly mirrors that of its histopathological features, it is suggested that the molecular profile of the tumour more accurately reflects the biological behaviour of the tumour (Kim et al, 2005). Therefore, individual biomarkers and linked molecular signatures such as those identified in our present study can clearly supplement standard clinical information to provide enhanced prognostication of RCC patients.…”

Section: Discussionmentioning

confidence: 67%

“…Therefore, individual biomarkers and linked molecular signatures such as those identified in our present study can clearly supplement standard clinical information to provide enhanced prognostication of RCC patients. To this end, two recent innovative studies have reported the development of a prognostic model that incorporates a panel of malignancy-associated biomarkers (which includes p53, CA9, Ki67, vimentin, CA12, PTEN and gelosin) with standard clinical parameters and where the resultant 'clinical/molecular marker' model, better predicts survival of patients with RCC (Kim et al, , 2005. Specifically, when ranked alongside several conventional RCC staging systems such as Fuhrman grade, TNM and ECOG-Performance Status (PS), the integrated 'clinical/molecular marker' prognostic model demonstrated superior prognostic value than either and/or that afforded by the panel of biomarkers alone.…”

Section: Discussionmentioning

confidence: 99%

Combined expression of caveolin-1 and an activated AKT/mTOR pathway predicts reduced disease-free survival in clinically confined renal cell carcinoma

et al. 2008

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We previously reported that tumour-associated caveolin-1 is a potential biomarker in renal cell carcinoma (RCC), whose overexpression predicts metastasis following surgical resection for clinically confined disease. Much attention has recently focused on the AKT/mTOR pathway in a number of malignancies, including RCC. Since caveolin-1 and the AKT/mTOR signalling cascade are independently shown to be important regulators of tumour angiogenesis, we hypothesised that caveolin-1 interacts with the AKT/ mTOR pathway to drive disease progression and metastasis in RCC. The aims of this study were to determine (i) the expression status of the activated AKT/mTOR pathway components (phosphorylated forms) in RCC and (ii) their prognostic value when combined with caveolin-1. Immunohistochemistry for caveolin-1, pAKT, pmTOR, pS6 and p4E-BP1 was performed on tissue microarrays from 174 clinically confined RCCs. Significantly decreased mean disease-free survival was observed when caveolin-1 was coexpressed with either pAKT (2.95 vs 6.14 years), pmTOR (3.17 vs 6.28 years), pS6 (1.45 vs 6.62 years) or p4E-BP1 (2.07 vs 6.09 years) than when neither or any one single biomarker was expressed alone. On multivariate analysis, the covariate of 'caveolin-1/AKT' (neither alone were influential covariates) was a significant influential indicator of poor disease-free survival with a hazard ratio of 2.13 (95% CI: 1.15 -3.92), higher than that for vascular invasion. Tumours that coexpressed caveolin-1 and activated mTOR components were more likely to be larger, higher grade and to show vascular invasion. Our results provide the first clinical evidence that caveolin-1 cooperates with an activated AKT/mTOR pathway in cancer and may play an important role in disease progression. We conclude that evaluation of the 'caveolin-1/AKT/mTOR axis' in primary kidney tumours will identify subsets of RCC patients who require greater postoperative surveillance and more intensive treatment.

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Using Tumor Markers to Predict the Survival of Patients With Metastatic Renal Cell Carcinoma

Abstract: 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.

Cited by 201 publications

References 17 publications

Carbonic Anhydrase IX is Not a Predictor of Outcomes in Non-Metastatic Clear Cell Renal Cell Carcinoma - A Digital Analysis of Tissue Microarray

Carbonic Anhydrase IX is Not a Predictor of Outcomes in Non-Metastatic Clear Cell Renal Cell Carcinoma - A Digital Analysis of Tissue Microarray

mTORC1 inhibitors: is temsirolimus in renal cancer telling us how they really work?

Combined expression of caveolin-1 and an activated AKT/mTOR pathway predicts reduced disease-free survival in clinically confined renal cell carcinoma

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