Department of Oncology, Vejle Hospital, Kabbeltoft 25, DK-7100 Vejle, Denmark.
BMC Cancer. 2010 May 7;10:185. doi: 10.1186/1471-2407-10-185.
Tissue inhibitor of metalloproteinase 1 (TIMP-1) is a natural inhibitor of the matrix metalloproteinases (MMPs) which are proteolytic enzymes involved in degradation of extracellular matrix thereby favoring tumour cell invasion and metastasis. TIMP-1 activity in tumour tissue may therefore play an essential role in the progression of a malignant tumour.The primary aim of the present study was to evaluate TIMP-1 protein immunoreactivity in tissue from primary ovarian cancer patients and associate these findings with the course of the disease including response to treatment in the individual patient.
TIMP-1 was assessed by immunohistochemistry (in tissue micro arrays) in a total of 163 ovarian cancer specimens obtained from primary debulking surgery during 1991-1994 as part of a randomized clinical protocol.
Positive TIMP-1 immunoreactivity was found in 12.3% of the tumours. The median survival time for the 143 patients with TIMP-1 negative tumours was 23.7 months [19.0-29.4] 95% CI, while the median survival time for the 20 patients with TIMP-1 positive tumours was 15.9 months [12.3-27.4] 95% CI. Although a difference of 7.8 months in median overall survival in favor of the TIMP-1 tumour negative patients was found, this difference did not reach statistical significance (p = 0.28, Kaplan-Meier, log-rank test). Moreover, TIMP-1 immunoreactivity was not associated with CA125 response (p = 0.53) or response at second look surgery (p = 0.72).
TIMP-1 immunoreactivity in tumour tissue from patients with primary epithelial ovarian cancer did not correlate with patient survival or response to combination platinum/cyclophosphamide therapy.
组织金属蛋白酶抑制剂 1（TIMP-1）是基质金属蛋白酶（MMPs）的天然抑制剂，MMPs 是参与细胞外基质降解的蛋白水解酶，从而有利于肿瘤细胞的侵袭和转移。因此，肿瘤组织中的 TIMP-1 活性可能在恶性肿瘤的进展中发挥重要作用。本研究的主要目的是评估原发性卵巢癌患者组织中 TIMP-1 蛋白的免疫反应性，并将这些发现与疾病的进程相关联，包括个体患者对治疗的反应。
在 1991-1994 年作为一项随机临床试验方案的一部分，通过免疫组织化学（组织微阵列）评估了总共 163 例原发性减瘤手术获得的卵巢癌标本中的 TIMP-1。
在 143 例 TIMP-1 阴性肿瘤患者中，有 12.3%的肿瘤呈 TIMP-1 阳性免疫反应性。TIMP-1 阴性肿瘤患者的中位生存时间为 23.7 个月[19.0-29.4]95%CI，而 TIMP-1 阳性肿瘤患者的中位生存时间为 15.9 个月[12.3-27.4]95%CI。尽管 TIMP-1 肿瘤阴性患者的总体生存时间中位数有 7.8 个月的差异，但这一差异没有达到统计学意义（p=0.28，Kaplan-Meier，对数秩检验）。此外，TIMP-1 免疫反应性与 CA125 反应（p=0.53）或二次探查手术的反应（p=0.72）无关。
原发性上皮性卵巢癌患者肿瘤组织中的 TIMP-1 免疫反应性与患者生存或对联合铂类/环磷酰胺治疗的反应无关。
