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Relative Expression of Type IV Collagenase, E-cadherin, and Vascular Endothelial Growth Factor/Vascular Permeability Factor in Prostatectomy Specimens Distinguishes Organ-confined from Pathologically Advanced Prostate Cancers¹

Departments of Cancer Biology [H. K., C. D. B., I. J. F., C. A. P.], Pathology, [P. T.], Biomathematics [D. J.], and Urology [C. A. P.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030-4095, and First Department of Pathology, Hiroshima University School of Medicine, Hiroshima, Japan [E. T.]

The tumor grade (Gleason score) in the biopsy and pretherapy prostate-specific antigen level do not accurately predict disease outcome of individual patients’ prostate cancer. We used a rapid colorimetric in situ hybridization technique to evaluate the expression level of E-cadherin (which affects cell cohesion); matrix metalloproteinases (MMPs) types 2 and 9 (which affect invasion); and vascular endothelial growth factor/vascular permeability factor (which affects angiogenesis) in archival prostatectomy specimens from 40 patients. Intratumoral heterogeneity for gene expression (edge versus center versus perineural area) was more pronounced in advanced cancers than in those that were organ confined. Regardless of Gleason score, the highest expression level for E-cadherin was found in the center or perineural area of the tumors, whereas the highest expression levels for MMP-2 and MMP-9 were associated with the invasive edge. The relationship between advancing pathological stage and expression of all four metastasis-related genes was highly significant. Decreased expression of E-cadherin and increased expression of MMP-2, MMP-9, and vascular endothelial growth factor/vascular permeability factor were associated with the Gleason score of the tumors. Irrespective of serum prostate-specific antigen level or Gleason score, the ratio between expression of MMPs and E-cadherin at the invasive edge of tumors exhibited the strongest association with nonorgan-confined prostate cancer. These data suggest that the relative expression of metastasis-related genes in radical prostatectomy specimens can distinguish between organ-confined and advanced prostate cancers and provides the rationale for a prospective study correlating gene expression in pretherapy core biopsies with outcome.

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