Validation of mammalian target of rapamycin biomarker panel in patients with clear cell renal cell carcinoma

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Haddad A.Q., Kapur P., Singla N., Raman J.D., Then M.T., Nuhn P., Buchner A., Bastian P., Seitz C., Shariat S.F., Bensalah K., Rioux-Leclercq N., Sagalowsky A., Lotan Y., Margulis V.

Cancer 2015 121:1 (43-50)

BACKGROUND: This was an external validation of the prognostic benefit of mammalian target of rapamycin (mTOR) marker panel in patients with clear cell renal cell carcinoma (ccRCC). METHODS: Immunohistochemistry for 5 mTOR pathway markers was performed on tissue microarrays of patients with nonmetastatic ccRCC treated surgically at 4 centers. The markers employed were phosphatase and tensin homolog (PTEN), phosphoinositide 3-kinase (PI3K), phosphorylated-mTOR (p-mTOR), phosphorylated-S6 (p-S6), and phosphorylated 4E-binding protein-1 (p-4EBP1). Cox regression was used to correlate marker status and oncologic outcomes. Discrimination of the models was determined using area under the curve and net reclassification improvement. RESULTS: Five hundred twenty-eight patients with a median follow-up of 56.5 months were included. Expression of PI3K, PTEN, p-mTOR, p-4EBP1, and p-S6 was altered in 52%, 78%, 25%, 86%, and 30% of patients, respectively…(vermás)


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