Increased activated Akt expression in renal cell carcinomas  and prognosis.
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.
Hager
Martina
M
Department of Pathology, Paracelsus Medical University (PMU), Salzburg, Austria.
Haufe
Heike
H
Department of Pathology, Paracelsus Medical University (PMU), Salzburg, Austria.
Kemmerling
Ralf
R
Department of Pathology, Paracelsus Medical University (PMU), Salzburg, Austria.
Hitzl
Wolfgang
W
Department of Research (Biostatistics), Paracelsus Medical University (PMU), Salzburg, Austria.
Mikuz
Gregor
G
Department of Pathology, Innsbruck Medical University (MUI), Innsbruck, Austria.
Moser
Patrizia L
PL
Department of Pathology, Innsbruck Medical University (MUI), Innsbruck, Austria.
Kolbitsch
Christian
C
Department of Anaesthesiology and Intensive Care Medicine, Innsbruck Medical University (MUI), Innsbruck, Austria.
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
D051057:Proto-Oncogene Proteins c-akt
J Surg Oncol. 2003 Nov;84(3):166-72
14598361
J Urol. 2003 Feb;169(2):710-3
12544348
Semin Urol Oncol. 2001 May;19(2):148-54
11354535
Am J Surg Pathol. 1982 Oct;6(7):655-63
7180965
Cell Cycle. 2003 Jul-Aug;2(4):339-45
12851486
Genes Dev. 1999 Nov 15;13(22):2905-27
10579998
Trends Biochem Sci. 2003 Nov;28(11):573-6
14607085
J Pathol. 2004 Sep;204(1):93-100
15307142
Int Braz J Urol. 2005 Jan-Feb;31(1):10-6
15763002
Clin Cancer Res. 2005 Apr 15;11(8):2930-6
15837744
Expert Rev Anticancer Ther. 2005 Dec;5(6):1031-40
16336094
Clin Cancer Res. 2004 Apr 15;10(8):2846-50
15102693
Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4240-5
10200246
Cancer. 2007 Jun 1;109(11):2257-67
17440983
Mod Pathol. 2004 Jan;17(1):15-21
14631376
Am J Pathol. 2001 Jun;158(6):2097-106
11395387
Biochim Biophys Acta. 2007 Oct;1772(10):1134-42
17681738
Blood. 2001 Nov 1;98(9):2853-5
11675360
Anticancer Drugs. 2005 Sep;16(8):797-803
16096426
Cancer. 2005 Dec 1;104(11):2430-6
16245318
Semin Cell Dev Biol. 2004 Apr;15(2):177-82
15209377
J Biol Chem. 1997 Dec 12;272(50):31515-24
9395488
J Pathol. 2005 Jun;206(2):214-9
15880754
Oncogene. 2003 May 22;22(21):3205-12
12761490
Cancer Res. 2001 May 15;61(10):3986-97
11358816
Ann Oncol. 2005 Jun;16(6):928-33
15851405
Am J Pathol. 1999 Oct;155(4):1253-60
10514407
Breast Cancer Res. 2003;5(2):R37-44
12631397
Expert Rev Anticancer Ther. 2007 Jun;7(6):863-70
17555396
J Clin Pathol. 2005 Nov;58(11):1199-205
16254112
Oncol Rep. 2005 Aug;14(2):389-92
16012720
Semin Oncol. 2001 Oct;28(5 Suppl 16):56-66
11706397
Cancer Res. 2001 Aug 15;61(16):6105-11
11507060
Histol Histopathol. 2003 Apr;18(2):551-5
12647806
Clin Genitourin Cancer. 2007 Sep;5(6):379-85
17956710