title: Increased activated Akt expression in renal cell carcinomas  and prognosis.
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.
authors.affiliation: Department of Pathology, Paracelsus Medical University (PMU), Salzburg, Austria.
authors.forename: Martina
authors.initials: M
authors.lastname: Hager
authors.affiliation: Department of Pathology, Paracelsus Medical University (PMU), Salzburg, Austria.
authors.forename: Heike
authors.initials: H
authors.lastname: Haufe
authors.affiliation: Department of Pathology, Paracelsus Medical University (PMU), Salzburg, Austria.
authors.forename: Ralf
authors.initials: R
authors.lastname: Kemmerling
authors.affiliation: Department of Research (Biostatistics), Paracelsus Medical University (PMU), Salzburg, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hitzl
authors.affiliation: Department of Pathology, Innsbruck Medical University (MUI), Innsbruck, Austria.
authors.forename: Gregor
authors.initials: G
authors.lastname: Mikuz
authors.affiliation: Department of Pathology, Innsbruck Medical University (MUI), Innsbruck, Austria.
authors.forename: Patrizia L
authors.initials: PL
authors.lastname: Moser
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, Innsbruck Medical University (MUI), Innsbruck, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Kolbitsch
mesh_terms: D002292:Carcinoma, Renal Cell / Q000201:enzymology*; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000201:enzymology*; D008297:Male; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D046888:Tissue Array Analysis
chemical_list: D051057:Proto-Oncogene Proteins c-akt
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