Reis Sabrina Thalita dos, Viana Nayara Izabel, Iscaife Alexandre, Pontes-Junior José, Dip Nelson, Antunes Alberto Azoubel, Guimarães Vanessa Ribeiro, Santana Isaque, Nahas William Carlos, Srougi Miguel, Leite Katia Ramos Moreira
Laboratorio de Investigacao Medica (LIM55), Departamento de Urologia da Universidade de Sao Paulo Faculdade de Medicina de Sao Paulo, Brasil.
Genoa Biotechnology SA, Sao Paulo, Brasil.
Int Braz J Urol. 2015 Nov-Dec;41(6):1088-95. doi: 10.1590/S1677-5538.IBJU.2014.0451.
Overexpression of MMPs has been related to biochemical recurrence after radical prostatectomy. TIMP1 and TIMP2 are controllers of MMPs and the aim of this study is to evaluate the expression levels of MMPs and their regulators using immunohistochemistry in tissue microarray of localized prostate cancer (PC).
Immune-expression of MMP-9, MMP-2, TIMP1, TIMP-2, MMP-14 and IL8, were analyzed by immunohistochemistry in radical prostatectomy specimens of 40 patients with localized PC who underwent surgery between September 1997 and February 2000. Protein expression was considered as categorical variables, negative or positive. The results of the immune-expression were correlated to Gleason score (GS), pathological stage (TNM), pre-operatory PSA serum levels and biochemical recurrence in a mean follow up period of 92.5 months.
The loss of TIMP1 immune-expression was related to biochemical recurrence. When TIMP1 was negative, 56.3% patients recurred versus 22.2% of those whose TIMP1 was positive (p=0.042). MMP-9, MMP-2, IL8 and MMP-14 were positive in the majority of PC. TIMP-2 was negative in all cases.
Negative immune-expression of TIMP1 is correlated with biochemical recurrence in patients with PC possibly by failing to control MMP-9, an important MMP related to cancer progression.
基质金属蛋白酶（MMPs）的过表达与前列腺癌根治术后的生化复发相关。金属蛋白酶组织抑制因子1（TIMP1）和金属蛋白酶组织抑制因子2（TIMP2）是MMPs的调控因子，本研究旨在通过免疫组织化学方法评估局限性前列腺癌（PC）组织芯片中MMPs及其调控因子的表达水平。
对1997年9月至2000年2月期间接受手术的40例局限性PC患者的前列腺癌根治术标本进行免疫组织化学分析，检测MMP-9、MMP-2、TIMP1、TIMP-2、MMP-14和白细胞介素8（IL8）的免疫表达。蛋白质表达被视为分类变量，分为阴性或阳性。免疫表达结果与 Gleason评分（GS）、病理分期（TNM）、术前血清前列腺特异抗原（PSA）水平以及平均随访92.5个月后的生化复发情况相关。
TIMP1免疫表达缺失与生化复发相关。当TIMP1为阴性时，56.3%的患者复发，而TIMP1为阳性的患者复发率为22.2%（p=0.042）。大多数PC中MMP-9、MMP-2、IL8和MMP-14呈阳性。所有病例中TIMP-2均为阴性。
PC患者中TIMP1的阴性免疫表达与生化复发相关，可能是由于未能控制MMP-9，MMP-9是一种与癌症进展相关的重要MMP。
