Loss of PTEN Immunoexpression Is Associated with Increased Risk of Recurrence after Prostatectomy for Clinically-Localized Prostate Cancer
Alcides Chaux, Sarah Peskoe, Nilda Gonzalez-Roibon, Jessica Hicks, Angelo M De Marzo, Elizabeth A Platz, George J Netto. Johns Hopkins University School of Medicine, Baltimore, MD; Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD
Background: PTEN is one of the most frequently lost tumor suppressor genes in human cancers. Specifically, loss of PTEN has been described in more than two-thirds of patients with prostate cancer, and several studies have suggested that PTEN loss is associated with tumor progression. The current study evaluates the prognostic role of PTEN loss as a predictive of recurrence following prostatectomy for clinically-localized prostate cancer, independent of known clinicopathological factors.
Design: PTEN expression was evaluated in a nested case-control study that included 451 cases (recurrence) and 451 controls (nonrecurrence). Patients were matched on Gleason grade, pathological stage, race/ethnicity, and age at surgery. All radical prostatectomies were performed at our institution between 1993 and 2001. Recurrence was defined as biochemical recurrence, development of clinical evidence of metastasis, or death from prostate carcinoma. Triplicate tumor samples per patient were used to build 16 tissue microarrays (TMAs). PTEN expression was evaluated using immunohistochemistry. Any TMA spot showing loss of PTEN expression, either focal or diffuse, was classified as “PTEN markedly decreased”. Additionally, an H-score was calculated as the sum of the products of stain intensity (0 to 3+) and extent (percentage) in each TMA spot and the mean H-score of all spots per case was used. Odds ratios (OR) of recurrence and 95% confidence intervals (95% CI) were estimated using conditional logistic regression to account for the matching factors, and to adjust for year of surgery, preoperative PSA concentrations, and status of surgical margins.
Results: Markedly decreased PTEN expression was observed in 62% percent of the recurrence cases and 53% of the nonrecurrence controls (P = .01). Men whose TMA spots all had markedly decreased PTEN expression had a 60% higher risk of recurrence (OR = 1.6; 95% CI 1, 2.5) when compared with all other men. The OR of recurrence was 2.2 (95% CI 1.3, 3.6; P = .002) comparing a mean H score < 10 to ≥ 10.
Conclusions: In patients treated by prostatectomy for clinically-localized prostate cancer, decreased immunohistochemical expression of PTEN is associated with an increased risk of recurrence, independent of known clinicopathological factors.
Category: Genitourinary (including renal tumors)
Monday, March 19, 2012 1:00 PM
Poster Session II # 145, Monday Afternoon