The ratio of matrix metalloproteinase to E‐cadherin expression: A pilot study to assess mRNA and protein expression among African American prostate cancer patients

Abstract

We assessed the expression of Matrix Metalloproteinase (MMP) to E-cadherin (M/E ratio) to determine the correlation of gene expression with pathologic variables and outcome in a cohort of African American (AA) prostate cancer patients. Tumors from formalin-fixed, paraffin embedded RP specimens were examined. Gleason scores were 6, 7, and >or=8 in 7, 16, 13 tumors, respectively. Pathologic stage was organ confined (pT2) in 18 and advanced (>pT2) in 18 tumors. A colorimetric mRNA in situ hybridization (ISH) assay was performed using biotinylated anti-sense oligonucleotide probes for MMP 2 and 9, as well as for E-cadherin gene transcripts. Immunohistochemistry (IHC) was performed utilizing specific monoclonal antibodies to detect the above genes. Image analysis was performed to determine the intensity of both mRNA and protein expression. Two reviewers analyzed ISH gene expression independently. The M/E expression ratio was significantly increased at the invasive edge (but not the center) of tumors of higher Gleason score (P = 0.02 and 0.0008) and pathologic stage (P = 0.0001 and <0.0001) when examined by both ISH and IHC. Significant variability in ISH staining interpretation was noted within and among the two study reviewers. An M/E ratio >2.5 was associated with biochemical recurrence after radical prostatectomy in addition to tumor pathologic stage subsequent to univariate statistical analysis. The M/E ratio characterizes an important aspect of the molecular phenotype associated with the histologic progression of prostate cancer among African American prostate cancer patients. A larger comparative study is required to determine potential racial variation and prognostic significance of gene expression.