BACKGROUND: Chronic inflammation may play a role in prostate carcinogenesis. Molecular alterations of the Suppressor of Cytokine Signaling (SOCS)-3 can contribute to explain the pleiotropic role of interleukin (IL)-6 in this type of cancer. Recently, the methylation of SOCS3 gene has been demonstrated to cause the non-expression of the protein, being involved in the pathogenesis of prostate cancer (PC) and identifying a subset of aggressive tumors. We evaluated the expression of SOCS3 protein in patients (pt) with bioptically-diagnosed PC by immunohistochemical analysis, which is easier to perform, cheaper and more reproducible compared to DNA analysis. METHODS: We analyzed the protein expression of SOCS3 by immunohistochemistry in 44 patients (pt) with PC diagnosed after biopsy. Slides were incubated with monoclonal antibody SOCS3 (1E4, 1.5 μg/mL; Abnova, Taiwan). The SOCS3 staining intensity was evaluated by two pathologists (FP and LML) in three different ways: positive (+), negative (-) and weak (+/-). Colonic mucosa was used as positive control. 36/44 patients underwent radical prostatectomy (RP). RESULTS: Biopsy Gleason score (Gs) was: <7 in 8 pt, 7 in 33 pt (3 + 4 pattern in 21 pt, 4 + 3 pattern in 12 pt), >7 in 3 pt. 8/8 (100%) pt with Gs <7 and 7/33 (21%) with Gs 7 were SOCS+. 15/33 (45%) pt with Gs 7 and 3/3 (100%) pt with Gs >7 were negative. In 11/33 pt (33%) Gs 7 a weak intensity was found so they were classified as SOCS3 +/-.25/36 (69%) patients who underwent RP were SOCS3- (15 pt with Gs 7(3 + 4), 7 pt with Gs 7(4 + 3), 3 pt with Gs 8) and 11/36 (30%) SOCS3+ (8 pt with Gs 6 and 3 pt with Gs 7(3 + 4)) (Tab 2). 12/25 (48%) SOCS3- pt had an organ-confined disease (≤pT2), whereas 13/25 (52%) had an extra prostatic neoplasm (5 pT3a (one was N+), 6 pT3b, 1 pT4). All SOCS3+ patients (8/8 (100%)) had an organ-confined disease. 3/3 (100%) SOCS3+/- pt had an extra prostatic neoplasm (>pT2). CONCLUSIONS: SOCS3- pt turned out to have a more aggressive disease compared with SOCS3+. In particular, also SOCS3+/- patients seemed to have an aggressive behavior. The non-expression of SOCS3 protein may identify PC with more aggressive behavior and can be evaluated with immunohystochemical analysis, which is a relatively easy and cheap procedure in clinical practice. These results, if confirmed by a wider population and a longer follow-up, may encourage the research on the use of this molecular family as a prognostic marker and a target for therapy with demethylating agents.
BACKGROUND: Chronic inflammation may play a role in prostate carcinogenesis. Molecular alterations of the Suppressor of Cytokine Signaling (SOCS)-3 can contribute to explain the pleiotropic role of interleukin (IL)-6 in this type of cancer. Recently, the methylation of SOCS3 gene has been demonstrated to cause the non-expression of the protein, being involved in the pathogenesis of prostate cancer (PC) and identifying a subset of aggressive tumors. We evaluated the expression of SOCS3 protein in patients (pt) with bioptically-diagnosed PC by immunohistochemical analysis, which is easier to perform, cheaper and more reproducible compared to DNA analysis. METHODS: We analyzed the protein expression of SOCS3 by immunohistochemistry in 44 patients (pt) with PC diagnosed after biopsy. Slides were incubated with monoclonal antibody SOCS3 (1E4, 1.5 μg/mL; Abnova, Taiwan). The SOCS3 staining intensity was evaluated by two pathologists (FP and LML) in three different ways: positive (+), negative (-) and weak (+/-). Colonic mucosa was used as positive control. 36/44 patients underwent radical prostatectomy (RP). RESULTS: Biopsy Gleason score (Gs) was: <7 in 8 pt, 7 in 33 pt (3 + 4 pattern in 21 pt, 4 + 3 pattern in 12 pt), >7 in 3 pt. 8/8 (100%) pt with Gs <7 and 7/33 (21%) with Gs 7 were SOCS+. 15/33 (45%) pt with Gs 7 and 3/3 (100%) pt with Gs >7 were negative. In 11/33 pt (33%) Gs 7 a weak intensity was found so they were classified as SOCS3 +/-.25/36 (69%) patients who underwent RP were SOCS3- (15 pt with Gs 7(3 + 4), 7 pt with Gs 7(4 + 3), 3 pt with Gs 8) and 11/36 (30%) SOCS3+ (8 pt with Gs 6 and 3 pt with Gs 7(3 + 4)) (Tab 2). 12/25 (48%) SOCS3- pt had an organ-confined disease (≤pT2), whereas 13/25 (52%) had an extra prostatic neoplasm (5 pT3a (one was N+), 6 pT3b, 1 pT4). All SOCS3+ patients (8/8 (100%)) had an organ-confined disease. 3/3 (100%) SOCS3+/- pt had an extra prostatic neoplasm (>pT2). CONCLUSIONS:SOCS3- pt turned out to have a more aggressive disease compared with SOCS3+. In particular, also SOCS3+/- patients seemed to have an aggressive behavior. The non-expression of SOCS3 protein may identify PC with more aggressive behavior and can be evaluated with immunohystochemical analysis, which is a relatively easy and cheap procedure in clinical practice. These results, if confirmed by a wider population and a longer follow-up, may encourage the research on the use of this molecular family as a prognostic marker and a target for therapy with demethylating agents.
Authors: Hao Yu; Yudong Liu; Braden C McFarland; Jessy S Deshane; Douglas R Hurst; Selvarangan Ponnazhagan; Etty N Benveniste; Hongwei Qin Journal: Cancer Immunol Res Date: 2015-02-03 Impact factor: 11.151
Authors: Fabiola Cecchi; Chih-Jian Lih; Young H Lee; William Walsh; Daniel C Rabe; Paul M Williams; Donald P Bottaro Journal: Clin Exp Metastasis Date: 2015-08-01 Impact factor: 5.150
Authors: Brian Thomas Joyce; Tao Gao; Lei Liu; Yinan Zheng; Siran Liu; Wei Zhang; Frank Penedo; Qi Dai; Joel Schwartz; Andrea A Baccarelli; Lifang Hou Journal: Cancer Epidemiol Biomarkers Prev Date: 2015-08-11 Impact factor: 4.254