Department of Pathology, Research Center, Centre Hospitalier Universitaire de Québec (CHUQ), Canada.
Hum Pathol. 2010 Dec;41(12):1694-701. doi: 10.1016/j.humpath.2010.05.001. Epub 2010 Sep 9.
Prostate cancer is the most common cancer in North American men. Among men diagnosed with prostate cancer in more than three cores or with high grade prostate cancer, many experience long disease-free survival. However, these patients still undergo radical treatment while they could benefit from active surveillance with complementary therapy. Matrix metalloproteinase 9 degrades type IV collagen and activates tumorigenic factors and is thus a potential prognostic factor and therapeutic target. This study was thus aimed at investigating the role of matrix metalloproteinase 9 on prostate cancer progression. We correlated matrix metalloproteinase 9 immunohistochemical expression by cancer, stromal and benign epithelial cells with prostate cancer disease-free survival among a cohort composed of 187 pT3NxM0 prostate cancer patients. Median follow-up was 4.63 years and a recurrence occurred in 67 men (35.3%). Matrix metalloproteinase 9 immunostaining was cytoplasmic and expressed at different levels in cancer (94.1%), stromal (87.7%) and benign epithelial cells (94.1%). High levels (>50% of cells) of matrix metalloproteinase 9 expression by prostate cancer cells was strongly associated with high Gleason score (P = .0009). In stromal cells and in benign epithelial cells, high matrix metalloproteinase 9 expression levels were respectively associated with low pT3 substage (P = .046) and with low initial serum prostate-specific antigen levels (P = .006). Matrix metalloproteinase 9 expression level by any cell type was not associated with prostate cancer disease-free survival. These results show that matrix metalloproteinase 9 is overexpressed by cancer cells in high grade tumors and by stromal and benign epithelial cells in lower substage tumors.
前列腺癌是北美男性最常见的癌症。在多针活检中发现 3 针以上或高级别前列腺癌的男性患者中,许多人经历了长期无疾病生存。然而,这些患者仍接受根治性治疗,而他们可能受益于辅助治疗的主动监测。基质金属蛋白酶 9 降解 IV 型胶原并激活致瘤因子,因此是一个潜在的预后因素和治疗靶点。本研究旨在研究基质金属蛋白酶 9 在前列腺癌进展中的作用。我们将由 187 例 pT3NxM0 前列腺癌患者组成的队列中,癌症、基质和良性上皮细胞的基质金属蛋白酶 9 免疫组织化学表达与无病生存相关联。中位随访时间为 4.63 年,67 名男性(35.3%)复发。基质金属蛋白酶 9 免疫染色为细胞质,在癌症(94.1%)、基质(87.7%)和良性上皮细胞(94.1%)中表达水平不同。癌细胞中基质金属蛋白酶 9 高表达(>50%的细胞)与高 Gleason 评分显著相关(P=0.0009)。在基质细胞和良性上皮细胞中,高基质金属蛋白酶 9 表达水平分别与 pT3 亚分期低(P=0.046)和初始血清前列腺特异性抗原水平低(P=0.006)相关。任何细胞类型的基质金属蛋白酶 9 表达水平与前列腺癌无病生存无关。这些结果表明,基质金属蛋白酶 9 在高级别肿瘤的癌细胞中过度表达,在低分期肿瘤的基质和良性上皮细胞中过度表达。