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Cancer Epidemiol Biomarkers Prev. 2013 Nov;22(11):1984-93. doi: 10.1158/1055-9965.EPI-13-0349. Epub 2013 Aug 27.

Protein expression of PTEN, insulin-like growth factor I receptor (IGF-IR), and lethal prostate cancer: a prospective study.

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Authors' Affiliations: Departments of Nutrition, Epidemiology, and Biostatistics, Harvard School of Public Health; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School; Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital; Departments of Pathology and Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts; Molecular and Transplantation Pathology Laboratory, F. Addarii Institute of Oncology, University of Bologna, Bologna, Italy; Center of Public Health Sciences, University of Iceland, Reykjavik, Iceland; The Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia; Department of Pathology & Laboratory Medicine and Oncology, University of Calgary, Calgary, Alberta; and Departments of Medicine and Oncology, McGill University, Jewish General Hospital, Montreal, Quebec, Canada.



Loss of PTEN has been shown to be associated with aggressive behavior of prostate cancer. It is less clear that loss of PTEN also increases the risk of cancer mortality. We investigated the association between PTEN expression and prostate cancer mortality and the potential effect modification by IGF-IR, a direct activator of the phosphoinositide-3-kinase (PI3K) pathway.


Protein expression in tumor was evaluated using tumor tissues obtained from 805 participants of the Physicians' Health and the Health Professionals Follow-up studies who were diagnosed with prostate cancer and underwent radical prostatectomy. Proportional hazard models were used to assess PTEN expression and its interaction with IGF-IR, in relation to lethal prostate cancer (cancer-specific death or distant metastases).


Low PTEN expression was associated with an increased risk of lethal prostate cancer [HR, 1.7; 95% confidence interval (CI), 0.98-3.2; Ptrend = 0.04]. The association was attenuated after adjustment for Gleason grade, tumor stage, and prostate-specific antigen (PSA) at diagnosis. A significant negative interaction between PTEN and IGF-IR was found (Pinteraction = 0.03). Either reduction in PTEN or increase in IGF-IR expression was sufficient to worsen prognosis. Models including PTEN and IGF-IR expression offer additional predicting power to prostate cancer survival, compared to those only including demographic and clinical factors.


Low PTEN protein expression significantly increases the risk of lethal prostate cancer, particularly when the IGF-IR expression remains at normal level.


PTEN and IGF-IR expression in tumor are promising candidates for independent prognostic factors to predict lethal prostate cancer.

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