SPINK1 Protein Expression and Prostate Cancer Progression.
Richard Flavin, Whitney Hendrickson, Lauren Krunz, Gregory Judson, Rosina Lis, Dyane Bailey, Michelangelo Fiorentino, Stephen Finn, Neil Martin, Jennifer Stark, Andreas Pettersson, Jennifer Sinnott, Kathyrn Penny, Katja Fall, Edward Giovannucci, Mark Rubin, Phillip Kantoff, Meir Stampfer, Massimo Loda, Lorelei Mucci. Dana Farber Cancer Institute/Harvard Cancer Center, Boston; Weill Cornell Medical College, New York
Background: Overexpression of SPINK1 (which is an inhibitor of serine proteases) has recently been described in prostate cancer. SPINK1 expression has been associated with poor prognosis in endocrine treated prostate cancer and in prostatectomy treated patients. Some groups suggest that SPINK1 outlier expression is a unique molecular subtype for men with TMPRSS2:ERG negative tumours identifying a separate mechanism of prostate cancer progression. The objective of this study was to characterize the aggressive phenotype (defined as PSA/biochemical recurrence) in SPINK1 positive prostate cancer in a large, prospective study.
Design: Protein expression of SPINK1 was evaluated semiquantitatively following immunohistochemistry using mouse monoclonal antibody (Abnova) on archival FFPE TMAs which included 962 cases of prostate cancer among men diagnosed in two large, prospective cohorts. TMPRSS2:ERG status, by chromosomal translocation or intronic deletion, was assessed by an ERG break-apart FISH assay(n=270). The men were followed for cancer progression and mortality through March 2010. Multivariable Cox regression models were used to estimate associations of SPINK1 and prostate cancer outcomes, adjusted for clinical factors.
Results: 15.5% of tumors were SPINK1 positive. SPINK1 protein expression was predominately mutually exclusive to the presence of the TMPRSS2:ERG fusion (97.5% of cases; p=0.0003; chi-square test). SPINK1 positive tumors had higher PSA at diagnosis (p=0.015) and higher Gleason score (p=0.04). SPINK1 protein expression had a small positive association with biochemical (PSA) recurrence on age adjusted analysis; Hazard Ratio 1.30(0.85-2.00; p>0.05). There was no association with lethal prostate cancer; Hazard Ratio 0.98(0.54-1.78; p=0.96).
Conclusions: SPINK1 protein tends to be exclusively expressed in tumours without the TMPRSS2:ERG fusion and is found in ∼15% of prostate cancers. SPINK1 positive prostate cancers may have a modest increased risk of prostate cancer progression.
Category: Genitourinary (including renal tumors)
Monday, February 28, 2011 1:00 PM
Poster Session II # 162, Monday Afternoon