Sienel Wulf, Polzer Bernhard, Elshawi Karimah, Lindner Michael, Morresi-Hauf Alicia, Vay Christian, Eder Fabian, Passlick Bernward, Klein Christoph A
Department of Thoracic Surgery, University Hospital Freiburg, Freiburg, Germany.
Mod Pathol. 2008 Sep;21(9):1130-8. doi: 10.1038/modpathol.2008.102. Epub 2008 Jun 20.
Extracellular matrix metalloproteinase (MMP) inducer (EMMPRIN, CD147) is a multifunctional protein that has been implicated in cancer invasion and metastasis by the induction of MMPs. To address its role in primary tumors of human non-small-cell lung cancer we assessed whether EMMPRIN expression is associated with the expression of MMP-2 and MMP-9 and with patient survival. Primary tumors of 150 patients (65 adenocarcinomas, 58 squamous cell carcinomas, and 27 of other subtypes) with completely resected lung cancers were stained by immunohistochemistry. We assessed intensity, extent, and cellular localization of EMMPRIN staining and determined MMP-2 and MMP-9 expression. 145 tumors expressed EMMPRIN (strong expression in 61 tumors), which was predominantly localized at the tumor cell membranes in 102 (68%) patients. We could not determine any correlation between EMMPRIN expression and MMP-2 or MMP-9 expression. The prognostic relevance of EMMPRIN was evaluated by Kaplan-Meier and multivariate Cox regression analysis in patients with adenocarcinoma (n=57) and squamous cell carcinoma of the lung (n=56). The median follow-up period was 36.0 months (range 4-156 months). Staining scores for EMMPRIN and MMP-2 and MMP-9 derived from staining intensities and percentages of positive cells did not predict outcome of patients. In contrast, univariate survival analysis demonstrated that membranous localization of EMMPRIN was associated with shortened survival in patients with adenocarcinoma (P=0.03; log-rank test), but not in squamous cell carcinoma. For the former patients, membranous EMMPRIN expression was also an independent predictor of patient survival (P=0.04; Cox regression analysis). The findings point to a role of EMMPRIN for the progression of adenocarcinoma of the lung that is unrelated to its function as inducer of MMPs.
细胞外基质金属蛋白酶（MMP）诱导剂（EMMPRIN，CD147）是一种多功能蛋白，通过诱导MMPs参与癌症侵袭和转移。为了研究其在人类非小细胞肺癌原发性肿瘤中的作用，我们评估了EMMPRIN表达是否与MMP - 2和MMP - 9的表达以及患者生存率相关。对150例肺癌完全切除患者（65例腺癌、58例鳞状细胞癌和27例其他亚型）的原发性肿瘤进行免疫组织化学染色。我们评估了EMMPRIN染色的强度、范围和细胞定位，并测定了MMP - 2和MMP - 9的表达。145个肿瘤表达EMMPRIN（61个肿瘤为强表达），其中102例（68%）患者主要定位于肿瘤细胞膜。我们未发现EMMPRIN表达与MMP - 2或MMP - 9表达之间存在任何相关性。通过Kaplan - Meier和多因素Cox回归分析评估EMMPRIN在腺癌（n = 57）和肺鳞状细胞癌（n = 56）患者中的预后相关性。中位随访期为36.0个月（范围4 - 156个月）。根据染色强度和阳性细胞百分比得出的EMMPRIN、MMP - 2和MMP - 9的染色评分不能预测患者的预后。相反，单因素生存分析表明，EMMPRIN的膜定位与腺癌患者的生存期缩短相关（P = 0.03；对数秩检验），但在鳞状细胞癌中不相关。对于前者患者，膜性EMMPRIN表达也是患者生存的独立预测因素（P = 0.04；Cox回归分析）。这些发现表明EMMPRIN在肺腺癌进展中发挥作用，这与其作为MMPs诱导剂的功能无关。
