title: Expression of matrix metalloproteinase-10 in non-metastatic prostate cancer: Correlation with an imbalance in cell proliferation and apoptosis.
abstract: Matrix metalloproteinases (MMPs) are associated with cell invasion under various physiological and pathological conditions. Among MMPs, MMP-10 is reported to correlate with a high pT stage and progression in a variety of cancer types. However, the clinical and pathological significance of MMP-10 in human prostate cancer tissues remains unclear. This study aimed to clarify the role of MMP-10 in non-metastatic prostate cancer. Sixty-three specimens were obtained by radical prostatectomy. MMP-10 expression, Ki-67, CD34 and apoptotic cells were examined using an immunohistochemical technique and the terminal deoxynucleotidyl transferase-mediated nick end-labeling method. The proliferation index (PI), apoptotic index (AI), microvessel density (MVD) and cell renewal index (CRI=PI/AI) were calculated. The relationship between MMP-10 expression and clinicopathological features, as well as PI, AI, MVD and CRI were investigated. MMP-10 was mainly detected in cancer cell cytoplasm, and the proportion of MMP-10-expressing cancer cells (median 13.8%) was significantly higher (P<0.001) than non-tumoral gland cells (2.4%). Similarly, the proportion of MMP-10-expressing cancer cells was significantly higher (P=0.007) in stage pT3 (median 22.3%) than in pT2 (11.3%) tumors and was correlated with blood vessel invasion (P=0.025). In addition, its expression level correlated significantly with CRI (r=0.34, P=0.001), but not with PI, AI or MVD. Multivariate analysis identified MMP-10 expression to be closely associated with pT stage (OR 3.76, 95% CI 1.14-12.34, P=0.029). Our results suggest that the overexpression of MMP-10 produces an imbalance in cancer cell proliferation and apoptosis, thereby contributing to cancer cell progression of non-metastatic prostate cancer.
authors.affiliation: Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Sugure
authors.initials: S
authors.lastname: Maruta
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Miyata
authors.forename: Yuji
authors.initials: Y
authors.lastname: Sagara
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kanda
authors.forename: Takahisa
authors.initials: T
authors.lastname: Iwata
authors.forename: Shin-Ichi
authors.initials: SI
authors.lastname: Watanabe
authors.forename: Hideki
authors.initials: H
authors.lastname: Sakai
authors.forename: Tomayoshi
authors.initials: T
authors.lastname: Hayashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kanetake