Racial Variation In The Matrix Metalloproteinase: E-Cadherin Ratio In Localized Prostate Cancer: Contemporary Matched Comparative Study

Main Category: Prostate / Prostate Cancer
Also Included In: Urology / Nephrology;  Cancer / Oncology
Article Date: 21 Jun 2008 - 10:00 PDT

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ORLANDO, FL (UroToday.com) - The ratio of Matrix metalloproteinase to E-cadherin (M/E ratio) characterizes the "invasive profile" of prostate cancer. In the present study a group of researchers from Houston performed a comparative analysis of the M/E ratio among Caucasian (CAU) and African- American (AA) patients undergoing radical prostatectomy (RP).

RP specimens (AA and CAU, N = 51 each) were used to create a tissue microarray where the dominant peripheral zone cancer focus for AA and CAU patients was Gleason score 7. AA and CAU patients were also matched for age, pathologic stage (pstage), serum PSA level, and year of surgery. Tissue cores were obtained from the tumor center, edge, and normal areas. Slides were subjected to in situ mRNA hybridization (ISH) with immunohistochemistry (IHC) using commercially available antibodies for MMP-2, MMP-9, and E-Cadherin. and the appropriate controls for both mRNA and protein expression. Image analysis was performed to quantitate gene expression levels which were normalized to the gene expression levels of normal tissue on the same slide. The M/E ratio was calculated by MMP-2 +MMP-9/2 ÷ E-cadherin. Wilcox rank sum tests were used to evaluate gene expression differences between groups.

The M/E ratio was higher among both AA and CAU patients with advanced (> stage pT3) versus organ confined (pT2) cancer when measured at the tumor edge and center by both ISH and IHC (ISH-edge =2.51 versus 1.32, p <0.0001, IHC-edge 2.32 versus 1.31, p<0.0001, ISH center =1.42 versus 1.15, p=0.002, IHC-center 1.45 vs. 1.25, p=0.006). Among patients with organ confined disease, tumors from AA men had significantly higher ratios compared to Caucasian men (ISH=1.51 and 1.07 respectively, p=0.0003, IHC=1.45 versus 1.21 respectively p=0.0007). While AA patients with pT3 cancer had significantly smaller tumors, the M/E ratio was similar to CAU patients (AA=2.28 versus CAU=2.97, p=0.08, IHC-AA 2.56 versus CAU 2.24, p=0.14).

They conclude that AA patients with organ confined cancer exhibited greater tumor M/E ratios compared to a matched CAU group. These data along with the presence of extraprostatic extension at smaller tumor volumes suggest that AA patients with early prostate cancer may have already developed a "molecular" phenotype that facilitates early tumor cell invasion.

Presented by Curtis A Pettaway, MD, Renduo Song, MD, Xuemei Wang, MD, Jun Liu, MD, Timothy McDonnell, MD, Peter C Black, MD, Ina Prokhorova, MD, Cindy Soto, MD, Sara Strom, MD, Patricia Troncoso, MD, at the Annual Meeting of the American Urological Association (AUA) - May 17 - 22, 2008. Orange County Convention Center - Orlando, Florida, USA.

Reported by UroToday.com Contributing Editor Christopher P. Evans, MD, FACS

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