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Measuring PI3K Activation : Clinicopathologic, Immunohistochemical, and RNA Expression Analysis in Prostate Cancer

Martin, Neil E. (författare)
Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Harvard Medical School, Boston MA, USA
Gerke, Travis (författare)
Department of Epidemiology, Harvard School of Public Health, Boston MA, USA
Sinnott, Jennifer A. (författare)
Department of Epidemiology, Harvard School of Public Health, Boston MA, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston MA, USA
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Stack, Edward C. (författare)
Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston MA, USA; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston MA, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston MA, USA
Andrén, Ove, 1963- (författare)
Örebro universitet,Institutionen för hälsovetenskap och medicin,Department of Urology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden
Andersson, Swen-Olof, 1949- (författare)
Örebro universitet,Institutionen för hälsovetenskap och medicin,Region Örebro län,Department of Urology, Örebro University Hospital, Örebro, Sweden
Johansson, Jan-Erik, 1946- (författare)
School of Health and Medical Sciences, Örebro University, Örebro, Sweden; Department of Urology, Örebro University Hospital, Örebro, Sweden
Fiorentino, Michelangelo (författare)
Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston MA, USA; Pathology Unit, Addarii Institute, S Orsola-Malpighi Hospital, Bologna, Italy
Finn, Stephen (författare)
Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston MA, USA; Department of Pathology, Trinity College, Dublin, Ireland
Fedele, Giuseppe (författare)
Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston MA, USA
Stampfer, Meir (författare)
Department of Epidemiology, Harvard School of Public Health, Boston MA, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston MA, USA
Kantoff, Philip W. (författare)
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston MA, USA
Mucci, Lorelei A. (författare)
Department of Epidemiology, Harvard School of Public Health, Boston MA, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston MA, USA
Loda, Massimo (författare)
Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston MA, USA; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston MA, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston MA, USA; Broad Institute of Harvard and MIT, Cambridge MA, USA; Division of Cancer Studies, King's College London, London, United Kingdom
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 (creator_code:org_t)
American Association for Cancer Research, 2015
2015
Engelska.
Ingår i: Molecular Cancer Research. - : American Association for Cancer Research. - 1541-7786 .- 1557-3125. ; 13:10, s. 1431-1440
Relaterad länk:
https://urn.kb.se/re...
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https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Nyckelord

Onkologi
Oncology

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