Values of Expression of SOCS-3 in Prostatic Biopsies
Francesco Pierconti, Tonia Cenci, Francesco Pinto, Pier Francesco Bassi, Luigi M Larocca. Catholic University of Sacred Heart, Rome, Italy
Background: In a recent study we found that the promoter of SOCS3 was methylated in 39.2% of prostate cancer, while all benign prostatic iperplasias (BPH) and normal controls had an unmethylated pattern. SOCS3 promoter methylation significantly associated with intermediate-high grade Gleason score and with an unfavorable clinical outcome. In order to validate our results in prostatic biopsies, we analyzed SOCS3 protein expression in a series of biopsies including BPH and prostatic adenocarcinoma.
Design: SOCS-3 protein expression was analyzed by immunhistochemistry in 20 BPH and in 90 prostate cancer biopsies: 54 prostatic carcinoma with Gleason score 7, 18 with Gleason score <7 and 18 with Gleason score >7. SOCS3 methylation status was analyzed with Methylation-Specific PCR (MSP-PCR). Slides were incubated with monoclonal antibody SOCS3 (1E4) (1.5 mg/ml; Abnova,Taiwan). The SOCS3 staining intensity were evaluated by two pathologist (FP and LML) in three different way: positive; negative; weak intensity (two different pattern: weak staining in all neoplastic glands and mixed areas with positive and negative neoplastic glands). Colonic mucosa were used as positive control. We statistically analyzed the correlation between our results and clinical data.
Results: SOCS3 positive staining were found in all cases of BPH, all cases of adenocarcinoma with Gleason score < 7 and in 14 cases with Gleason score 7, negative staining were found in all cases of adenocarcinoma Gleason score > 7 and in 10 cases with Gleason score 7. Weak SOCS3 staining were found in 30 cases of adenocarcinoma Gleason score 7. Tumors SOCS3 negative were significantly more aggressive than SOCS3 positive ones in terms of TNM stage and positivity of surgical margin. Moreover, among cases with Gleason score 7, negative staining of SOCS3 identifies a subgroup of tumor with more aggressive clinical behavior (increase number of T3) than positive ones.
Conclusions: In prostatic biopsies immunohistochemical analysis of SOCS3 protein identify among prostatic adenocarcinoma Gleason score 7:
A subgroup of tumor negative staining for SOCS3 with aggressive clinical behavior and thus object of strict follow-up and suitable to demethylating agents therapy.
A subgroup of tumors with weak SOCS3 staining, not identified by methylathion analysis, probably corresponding to an intermediate stage of tumor turning towards shutdown of SOCS3, whose clinical behavior requires a long follow-up to be clearly evaluated.
Category: Genitourinary (including renal tumors)
Monday, March 19, 2012 1:00 PM
Poster Session II # 184, Monday Afternoon