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.
Written by:
Calarco A, Pinto F, Pierconti F, Sacco E, Marrucci E, Totaro A, Palermo G, Vittori M, Bassi P. Are you the author?
Catholic University School of Medicine "A. Gemelli" Hospital, Urology Department, Rome, Italy.
Reference: Urologia. 2012 Jul 13;0(0):0.
doi: 10.5301/RU.2012.9392
PubMed Abstract
PMID: 22865333
UroToday.com Investigative Urology Section
