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The Relative mRNA Expression Levels of Matrix Metalloproteinase to E-Cadherin in Prostate Biopsy Specimens Distinguishes Organ-confined from Advanced Prostate Cancer at Radical Prostatectomy¹

Department of Oncological Pathology, Cancer Center, Nara Medical University, Kashihara, Japan [H. K.]; JR Hiroshima General Hospital of West Japan Railway Company, Hiroshima, Japan [R. U.]; and the Departments of Biomathematics [D. J.], Pathology [P. T.], Cancer Biology and [I. J. F., C. A. P.], and Urology [C. A. P.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

Purpose: To determine whether the expression ratio of matrix metalloproteinase (MMP) to E-cadherin mRNA (MMP:E-cadherin) in biopsy (BX) samples of prostate cancer correlate with that of radical prostatectomy (RP) specimens and assists in predicting pathologic stage.

Experimental Design: The mRNA expression levels for MMP-2 and -9 and of E-cadherin were determined by a colorimetric in situ hybridization assay in 44 paired BX and RP specimens. Clinical stage, BX Gleason score (GS), total length of cancer in BX cores, and serum prostate-specific antigen levels were also assessed.

Results: Clinical stage was confined in 39 of 44 (89%) patients. Subsequent to RP, however, only 17 of 44 (39%) patients had proven organ-confined disease (pT2). BX GSs agreed with the RP GS in 77% of RP specimens. We found a strong correlation between BX and RP MMP:E-cadherin ratios (correlation coefficient = 0.755). The ratio increased as the GS increased and pathologic stage advanced (pT2 versus ≥ pT3). Increasing clinical stage, GS, and serum prostate-specific antigen were significantly associated with advanced cancer at RP (P = 0.004–0.0001). The BX MMP:E-cadherin ratio, however, exhibited the strongest association with pathologic stage and independently predicted the status of 89% of the RP cases based on a BX ratio of <6 (predicted stage pT2 cancer at RP) versus ≥6 (predicted stage ≥ pT3 at RP).

Conclusion: The BX MMP:E-cadherin ratio represents a novel prognostic assay for predicting stage of cancer at RP. These data provide proof of principle for directly assessing the biological potential of prostate cancer using molecular strategies in patient’s specimens.

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