EMMPRIN (extracellular matrix metalloproteinase inducer) is a novel marker of poor outcome in serous ovarian carcinoma
EMMPRIN (extracellular matrix metalloproteinase inducer) is a novel marker of poor outcome in serous ovarian carcinoma
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DOI：
10.1023/a:1022696012668
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发表时间：
2003-01-01
影响因子：
4
通讯作者：
Reich, R
中科院分区：
文献类型：
--
作者：
Davidson, B;Goldberg, I;Reich, R
EMMPRIN是粘附分子的免疫球蛋白超家族的成员，并在几种基质金属蛋白酶（MMP）的活化中起作用。本研究的目的是研究EMMPRIN在浆液性卵巢癌患者的渗出液、原发性和转移性肿瘤中的表达，并评估其与临床病理参数以及MMP和整合素表达的相关性。采用原位杂交（ISH）对80例积液和83例实体性病变的EMMPRIN mRNA表达进行了评价。采用免疫组化（IHC）研究了75例积液和55例活检组织中的蛋白表达。EMMPRIN mRNA和蛋白在63/80（79%）和64/75（85%）的癌细胞中分别检测到。在腹腔积液和胸腔积液中表达相似。EMMPRIN与MMP-1（P < 0.001）、MMP-9（P = 0.006）及αv（P = 0.013）、β1（P = 0.029）整合素亚基共表达。在实体性病变中，EMMPRIN最常定位于肿瘤细胞（使用ISH的51/83，使用IHC的51/55），但在约三分之一的病例中也在基质和内皮细胞中表达。EMMPRIN mRNA在腹膜转移癌中表达最高（P = 0.03）。EMMPRIN在实体瘤中的表达与MMP-9的表达相关（P = 0.018），而基质细胞中的EMMPRIN与β1整合素亚基的表达呈共定位（P = 0.043）。在生存分析中，EMMPRIN蛋白在原发性肿瘤的基质细胞（P = 0.012）和所有实体瘤的内皮细胞（P = 0.023）中的表达与不良生存相关。总之，EMMPRIN是卵巢癌的一种新的预后标志物，并且在这种恶性肿瘤中与其他转移相关分子共表达。胸腔积液和腹腔积液中癌细胞的相同表型为我们的理论提供了进一步的证据，即这些部位的细胞具有相似的基因型和表型特征。
EMMPRIN is a member of the immunoglobulin superfamily of adhesion molecules and has a role in the activation of several matrix metalloproteinases (MMP). The objective of this study was to investigate the expression of EMMPRIN in effusions, primary and metastatic tumors of serous ovarian carcinoma patients, as well as to evaluate its association with clinicopathologic parameters and with MMP and integrin expression. Eighty effusions and eighty-three solid lesions were evaluated for expression of EMMPRIN mRNA using in situ hybridization (ISH). Protein expression was studied in 75 effusions and 55 biopsies using immunohistochemistry (IHC). EMMPRIN mRNA and protein were detected in carcinoma cells in 63/80 (79%) and 64/75 (85%) effusions, respectively. Expression was similar in peritoneal and pleural effusions. EMMPRIN was co-expressed with MMP-1 (P < 0.001), MMP-9 (P = 0.006) and the αv (P = 0.013) and β1 (P = 0.029) integrin subunits. In solid lesions, EMMPRIN localized most often to tumor cells (51/83 using ISH 51/55 using IHC), but was also expressed in stromal and endothelial cells in approximately one third of the cases. EMMPRIN mRNA expression in tumor cells was most frequent in peritoneal metastases (P = 0.03). EMMPRIN expression in carcinoma cells of solid tumors showed an association with that of MMP-9 (P = 0.018), while labeling of stromal cells showed co-localization with the β1 integrin subunit (P = 0.043). In survival analysis, EMMPRIN protein expression in stromal cells of primary tumors (P = 0.012) and in endothelial cells of all solid tumors (P = 0.023) correlated with poor survival. In conclusion, EMMPRIN is a novel prognostic marker in ovarian carcinoma, and is co-expressed with other metastasis-associated molecules in this malignancy. The identical phenotype of carcinoma cells in pleural and peritoneal effusions provides further evidence to our theory that cells at these sites share similar genotypic and phenotypic profiles.