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Measuring PI3K Activation: Clinicopathologic, Immunohistochemical, and RNA Expression Analysis in Prostate Cancer
Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
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2015 (English)In: Molecular Cancer Research, ISSN 1541-7786, E-ISSN 1557-3125, Vol. 13, no 10, 1431-1440 p.Article in journal (Refereed) Published
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Abstract [en]

Assessing the extent of PI3K pathway activity in cancer is vital to predicting sensitivity to PI3K-targeting drugs, but the best biomarker of PI3K pathway activity in archival tumor specimens is unclear. Here, PI3K pathway activation was assessed, in clinical tissue from 1,021 men with prostate cancers, using multiple pathway nodes that include PTEN, phosphorylated AKT (pAKT), phosphorylated ribosomal protein S6 (pS6), and stathmin. Based on these markers, a 9-point score of PI3K activation was created using the combined intensity of the 4-markers and analyzed its association with proliferation (Ki67), apoptosis (TUNEL), and androgen receptor (AR) status, as well as pathologic features and cancer-specific outcomes. In addition, the PI3K activation score was compared with mRNA expression profiling data for a large subset of men. Interestingly, those tumors with higher PI3K activation scores also had higher Gleason grade (P = 0.006), increased AR (r = 0.37; P < 0.001) and Ki67 (r = 0.24; P < 0.001), and decreased TUNEL (r = -0.12; P = 0.003). Although the PI3K activation score was not associated with an increased risk of lethal outcome, a significant interaction between lethal outcome, Gleason and high PI3K score (P = 0.03) was observed. Finally, enrichment of PI3K-specific pathways was found in the mRNA expression patterns differentiating the low and high PI3K activation scores; thus, the 4-marker IHC score of PI3K pathway activity correlates with features of PI3K activation.

Place, publisher, year, edition, pages
American Association for Cancer Research , 2015. Vol. 13, no 10, 1431-1440 p.
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
URN: urn:nbn:se:oru:diva-47170DOI: 10.1158/1541-7786.MCR-14-0569ISI: 000365604300008PubMedID: 26124442Scopus ID: 2-s2.0-84945245876OAI: oai:DiVA.org:oru-47170DiVA: diva2:885838
Note

Funding Agencies:

Dana-Farber/Harvard Cancer Center Specialized Programs of Research Excellence (SPORE) in Prostate Cancer P50CA090381-08

National Cancer Institute of the NIH UM1CA167552  R01CA141298  R01CA136578  R01CA131945  P01CA89021

Prostate Cancer Foundation Young Investigator awards

Available from: 2015-12-21 Created: 2015-12-21 Last updated: 2017-10-18Bibliographically approved

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Andrén, OveAndersson, Swen-OlofJohansson, Jan-Erik
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School of Health and Medical Sciences, Örebro University, SwedenÖrebro University Hospital
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