Yoshikawa Takaki, Tsuburaya Akira, Kobayashi Osamu, Sairenji Motonori, Miyagi Yohei
Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan.
Gastric Cancer. 2006;9(2):106-13. doi: 10.1007/s10120-006-0362-y.
Tissue inhibitor of metalloproteinase-1 (TIMP-1) correlates with tumor progression in patients with gastric cancer; however, the clinical significance of TIMP-1 as a marker for prognosis and recurrence has not been fully clarified.
TIMP-1 protein was measured by an enzyme-linked immunosorbent assay in tumor samples from 86 patients who had undergone surgical resection. An intratumoral TIMP-1 value of 10.0 ng/mg protein or more was defined as positive. Patients were followed up for more than 5 years prospectively.
Thirty-one of the 86 patients (36.0%) were positive for TIMP-1. Kaplan-Meier curves for overall survival were significantly different between patients who were positive and those who were negative for TIMP-1. Univariate analysis of factors affecting overall survival showed that depth of tumor invasion; lymph node metastasis; peritoneal dissemination; lymphatic invasion; venous invasion; Lauren classification of histology; curability; and TIMP-1 were statistically significant. Stepwise multivariate analysis for overall survival demonstrated that depth of tumor invasion, nodal metastasis, peritoneal dissemination, and TIMP-1 remained independent prognostic factors. Kaplan-Meier curves for disease-free survival were significantly different between patients who were positive and those who were negative for TIMP-1. The incidence of recurrence was significantly higher in patients positive for TIMP-1 than in those who were negative for TIMP-1. The frequency at each site of recurrence was higher in patients positive for TIMP-1.
These results suggested that the protein concentration of TIMP-1 in the tumor extracts was a useful marker for overall survival, disease-free survival, and disease recurrence in patients with gastric cancer. Thus, tumor TIMP-1 may serve to identify a high-risk group, for whom optimal surgical and medical treatment can be given.
基质金属蛋白酶-1组织抑制剂（TIMP-1）与胃癌患者的肿瘤进展相关；然而，TIMP-1作为预后和复发标志物的临床意义尚未完全阐明。
采用酶联免疫吸附测定法检测86例行手术切除患者肿瘤样本中的TIMP-1蛋白。肿瘤内TIMP-1值≥10.0 ng/mg蛋白定义为阳性。对患者进行前瞻性随访5年以上。
86例患者中有31例（36.0%）TIMP-1呈阳性。TIMP-1阳性和阴性患者的总生存Kaplan-Meier曲线有显著差异。影响总生存的因素单因素分析显示，肿瘤浸润深度、淋巴结转移、腹膜播散、淋巴管浸润、静脉浸润、Lauren组织学分类、可治愈性和TIMP-1具有统计学意义。总生存的逐步多因素分析表明，肿瘤浸润深度、淋巴结转移、腹膜播散和TIMP-1仍然是独立的预后因素。TIMP-1阳性和阴性患者的无病生存Kaplan-Meier曲线有显著差异。TIMP-1阳性患者的复发率显著高于阴性患者。TIMP-1阳性患者各复发部位的频率更高。
这些结果表明，肿瘤提取物中TIMP-1的蛋白浓度是胃癌患者总生存、无病生存和疾病复发的有用标志物。因此，肿瘤TIMP-1可用于识别高危人群，以便给予最佳的手术和药物治疗。
