Mori M, Mimori K, Sadanaga N, Inoue H, Tanaka Y, Mafune K, Ueo H, Barnard G F
Department of Surgery, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan.
Int J Cancer. 2000 Nov 15;88(4):575-8. doi: 10.1002/1097-0215(20001115)88:4<575::aid-ijc9>3.0.co;2-c.
Tissue inhibitor of metalloproteinase-1 (TIMP-1) inhibits the activity of matrix metalloproteinase, which may play an important role in carcinoma invasion and metastasis. TIMP-1 is thus considered to inhibit carcinoma invasion and metastasis. However, TIMP-1 possesses another important function, cell growth promotion. The clinical significance of TIMP-1 expression has not been fully determined in esophageal carcinoma. We thus examined the expression of TIMP-1 mRNA in tumor (T) and corresponding normal (N) tissues of 85 esophageal carcinoma cases by RT-PCR. The T:N ratio of TIMP-1 mRNA expression in each case was evaluated semi-quantitatively with adjustment by an internal control gene. The mean T:N ratio was 2.0 (range 0.2-6.5). When comparing high-expression cases (T:N > 2.0, n = 37) with low-expression cases (T:N < or = 2.0, n = 48), the former showed a significantly higher frequency of lymph vessel invasion, vascular vessel invasion, lymph node metastasis and advanced-stage disease. The former cases showed a poorer prognosis than the latter. Multivariate analysis disclosed that TIMP-1 expression status was an independent determining factor for prognosis. Our findings suggest that TIMP-1 expression correlates with tumor extension of esophageal carcinoma and might, if validated, prove useful as a novel prognostic marker for esophageal carcinoma.
基质金属蛋白酶-1组织抑制剂（TIMP-1）可抑制基质金属蛋白酶的活性，这可能在癌侵袭和转移中发挥重要作用。因此，TIMP-1被认为可抑制癌侵袭和转移。然而，TIMP-1还具有另一重要功能，即促进细胞生长。TIMP-1表达在食管癌中的临床意义尚未完全明确。因此，我们采用逆转录聚合酶链反应（RT-PCR）检测了85例食管癌患者肿瘤（T）组织及相应正常（N）组织中TIMP-1 mRNA的表达。通过内部对照基因调整，对每例患者TIMP-1 mRNA表达的T:N比值进行半定量评估。TIMP-1 mRNA表达的平均T:N比值为2.0（范围0.2 - 6.5）。将高表达病例（T:N > 2.0，n = 37）与低表达病例（T:N ≤ 2.0，n = 48）进行比较时，前者在淋巴管浸润、血管浸润、淋巴结转移及疾病晚期方面的发生率显著更高。前者的预后比后者更差。多因素分析显示，TIMP-1表达状态是预后的独立决定因素。我们的研究结果表明，TIMP-1表达与食管癌的肿瘤进展相关，若得到验证，可能作为一种新的食管癌预后标志物。
