PMID- 21792700 OWN - NLM STAT- MEDLINE DCOM- 20120731 LR - 20211203 IS - 1532-2807 (Electronic) IS - 1219-4956 (Linking) VI - 18 IP - 2 DP - 2012 Apr TI - pS6 Expression in normal renal parenchyma, primary renal cell carcinomas and their metastases. PG - 277-83 LID - 10.1007/s12253-011-9439-y [doi] AB - In cancer therapy novel concepts focus on phosphoinositide-3-kinase/protein kinase B/mammalian target of rapamycin (mTOR) inhibitors. In this context, phosphorylated S6 protein of the 40S ribosomal subunit (pS6) overexpression was previously shown to be associated with sensitivity to inhibitors of mTOR. The present study therefore evaluated pS6 expression in normal renal parenchyma (NRP), primary renal cell carcinomas (PRCC) and their metastases. pS6 and pmTOR expression was immunohistochemically analyzed in a tissue microarray (TMA) from localized primary renal cell carcinoma (lPRCC) (n = 35), metastasized primary renal cell carcinoma (mPRCC) (n = 45), their metastases (n = 45), and NRP (n = 45). pS6 expression was stronger in mPRCCs and metastases than in NRP and lPRCCs (p < 0.05). In mPRCCs high-grade and high-stage tumors showed higher pS6 levels. pS6 overexpression was more frequently found in metastases (40/45; 88.9%) than in mPRCC (24/45; 53.3%) (p < 0.05). Overexpression of pS6 in metastases without concomitant overexpression in their primary tumors was found in 16/45 (35.56%) cases. Patients with pS6 overexpression in mPRCCs but also in metastases showed a tendency to shorter overall survival. pS6 score and pmTOR score correlated positively in NRP and in tumorous tissue (mPRCC and metastases). In conclusion, the present study showed stronger pS6 expression and more frequent overexpression in metastases than in corresponding PRCCs. In approximately one-third of the cases pS6 overexpression was found exclusively in metastases, which is interesting with regard to the association between high pS6 expression and sensitivity to mTOR inhibitor therapy. FAU - Hager, Martina AU - Hager M AD - Department of Pathology, Paracelsus Medical University (PMU), Muellner Hauptstrasse 48, 5020, Salzburg, Austria. hager.martina@gmx.at FAU - Haufe, Heike AU - Haufe H FAU - Alinger, Beate AU - Alinger B FAU - Kolbitsch, Christian AU - Kolbitsch C LA - eng PT - Comparative Study PT - Journal Article DEP - 20110727 PL - Switzerland TA - Pathol Oncol Res JT - Pathology oncology research : POR JID - 9706087 RN - 0 (Ribosomal Protein S6) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Carcinoma, Papillary/metabolism/secondary MH - Carcinoma, Renal Cell/*metabolism/*secondary MH - Case-Control Studies MH - Female MH - Humans MH - Immunoenzyme Techniques MH - Kidney/*metabolism/pathology MH - Kidney Neoplasms/*metabolism/*pathology MH - Male MH - Middle Aged MH - Neoplasm Staging MH - Prognosis MH - Ribosomal Protein S6/*metabolism MH - Survival Rate MH - TOR Serine-Threonine Kinases/metabolism MH - Tissue Array Analysis EDAT- 2011/07/28 06:00 MHDA- 2012/08/01 06:00 CRDT- 2011/07/28 06:00 PHST- 2010/12/29 00:00 [received] PHST- 2011/07/11 00:00 [accepted] PHST- 2011/07/28 06:00 [entrez] PHST- 2011/07/28 06:00 [pubmed] PHST- 2012/08/01 06:00 [medline] AID - 10.1007/s12253-011-9439-y [doi] PST - ppublish SO - Pathol Oncol Res. 2012 Apr;18(2):277-83. doi: 10.1007/s12253-011-9439-y. Epub 2011 Jul 27.