Expression of the serine protease matriptase and its inhibitor HAI-1 in epithelial ovarian cancer: correlation with clinical outcome and tumor clinicopathological parameters.
Expression of the serine protease matriptase and its inhibitor HAI-1 in epithelial ovarian cancer: correlation with clinical outcome and tumor clinicopathological parameters.
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发表时间：
2002-04
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通讯作者：
M. Oberst;Michael D. Johnson;R. Dickson;Chen-Yong Lin;Baljit Singh;M. Stewart;Alastair Williams
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作者：
M. Oberst;Michael D. Johnson;R. Dickson;Chen-Yong Lin;Baljit Singh;M. Stewart;Alastair Williams
目的：Mattritase是一种II型跨膜型丝氨酸蛋白酶，由表面上皮源性细胞表达，包括卵巢上皮性肿瘤细胞。Mattritase切割并激活与卵巢癌进展有关的蛋白，代表了一个潜在的预后和治疗靶点。本研究的目的是检测Mattritase及其抑制物肝细胞生长因子激活物抑制物-1(HAI-1)在上皮性卵巢癌中的表达，并探讨其与临床病理的关系。实验设计采用免疫组织化学方法检测54例上皮性卵巢癌组织中基质金属蛋白酶和HAI-1的表达。然后对免疫组织化学表达数据与临床结果和临床病理参数进行统计分析。结果54例肿瘤中，Mattritase阳性39例(72%)，HAI-1阳性11例(20%)。所有HAI-1阳性的肿瘤均为Mattritase阳性。临床病理参数分析显示，与I/II期肿瘤相比，III/IV期肿瘤中Mattritase基因缺失(P=0.030)。与III/IV期肿瘤相关的HAI-1表达缺失(P=0.039)。34例I/II期肿瘤中，28例(82%)Mattritase表达阳性，10例(29%)HAI-1表达阳性，10例(29%)同时表达。然而，在20例III/IV期肿瘤中，11例Mattritase阳性(55%)，其中仅1例同时表达HAI-1(P=0.039)。结论晚期卵巢肿瘤在缺乏其抑制物HAI-1的情况下更容易表达Mattritase，提示Mattritase/HAI-1比例的失衡可能在晚期疾病的发生发展中起重要作用。这种不平衡可能会促进Mattritase的蛋白分解活性，从而产生更具侵袭性的表型。
PURPOSE Matriptase is a type II transmembrane serine protease expressed by cells of surface epithelial origin, including epithelial ovarian tumor cells. Matriptase cleaves and activates proteins implicated in the progression of ovarian cancer and represents a potential prognostic and therapeutic target. The aim of this study was to examine the expression of matriptase, and its inhibitor, hepatocyte growth factor activator inhibitor-1 (HAI-1), in epithelial ovarian cancer and to assign clinicopathological correlations. EXPERIMENTAL DESIGN We have determined by immunohistochemistry the expression of matriptase and HAI-1 in 54 epithelial ovarian cancers. Statistical analyses of immunohistochemistry expression data with clinical outcome and clinicopathological parameters were then performed. RESULTS Of 54 tumors tested, 39 (72%) and 11 (20%) were positive for matriptase and for HAI-1, respectively. All HAI-1-positive tumors were also matriptase positive. Analysis of clinicopathological parameters demonstrated a loss of matriptase associated with stage III/IV tumors as compared with stage I/II tumors (P = 0.030). There was also a loss of HAI-1 expression associated with stage III/IV tumors (P = 0.039). Of 34 stage I/II tumors, 28 (82%) stained positive for matriptase, and 10 (29%) stained positive for HAI-1; 10 (29%) tumors showed coexpression. Of 20 stage III/IV tumors, however, 11 stained positive for matriptase (55%), only 1 of which coexpressed HAI-1 (P = 0.039). CONCLUSIONS Advanced-stage ovarian tumors that express matriptase are more likely to do so in the absence of its inhibitor, HAI-1, indicating that an imbalance in the matriptase:HAI-1 ratio could be important in the development of advanced disease. Such an imbalance could promote the proteolytic activity of matriptase and, consequently, a more invasive phenotype.