Portal de Periódicos da CAPES

Increased activated Akt expression in renal cell carcinomas and prognosis

2008; Wiley; Volume: 13; Issue: 8b Linguagem: Inglês

10.1111/j.1582-4934.2008.00488.x

1582-4934

Martina Hager, Heike Haufe, Ralf Kemmerling, Wolfgang Hitzl, Gregor Mikuz, Patrizia Moser, Christian Kolbitsch,

Cancer Mechanisms and Therapy

Abstract Renal carcinogenesis is promoted by overexpression of the activated serine/threonine kinase Akt (p‐Akt) and supposedly a concomitant reduction in phosphatase and tensin homologue deleted on chromosome 10 tumour suppressor gene (PTEN), which normally inhibits the activation of Akt. Because promising anti‐cancer therapies increasingly focus on pathways involving p‐Akt and PTEN, the present study evaluated the expression of p‐Akt in renal cell carcinomas and compared it with prognosis. P‐Akt and PTEN expression were analysed in a tissue microarray (TMA) from renal cell carcinoma ( n = 386) and adjacent uninvolved renal tissue ( n = 32) specimens. Increased p‐Akt was found more often in the nucleus than in the cytoplasm, and PTEN was concomitantly reduced in about 50% of cases. Neither tumour grade nor stage influenced p‐Akt expression, whereas the clear cell and papillary subtypes showed increased p‐Akt more often than did the chromophobe or sarcomatoid types. Increased cytoplasmic and nuclear p‐Akt levels were independent prognostic factors for diminishing patient survival. The present study found significantly increased nuclear but also cytoplasmic p‐Akt expression in renal cell carcinoma subtypes. Increased nuclear and cytoplasmic p‐Akt was an independent prognostic factor for diminishing patient survival. The considerable number of high‐grade and high‐stage RCC showing increased p‐Akt and reduced PTEN would justify further evaluation of therapeutic concepts based on inhibitors of the PI3K/p‐Akt/mTOR pathway.