EMMPRIN expression as a prognostic factor in radiotherapy of cervical cancer
EMMPRIN expression as a prognostic factor in radiotherapy of cervical cancer
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EMMPRIN 表达作为宫颈癌放疗的预后因素
DOI：
10.1158/1078-0432.ccr-07-1072
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发表时间：
2008-01-15
影响因子：
11.5
通讯作者：
Wu, Xiao-Hua
中科院分区：
文献类型：
--
作者：
Ju, Xing-Zhu;Yang, Jin-Ming;Wu, Xiao-Hua
目的：细胞外基质金属蛋白酶诱导因子（EMMPRIN）是免疫球蛋白家族的一员，是一种在多种肿瘤细胞表面富集的糖蛋白，其过表达与肿瘤细胞的侵袭、转移、生长和存活有关。宫颈癌是全球妇女中第二大流行癌症，也是癌症死亡的第五大原因，对放射治疗有反应，30%的病例在治疗后复发。本研究的目的是确定EMMPRIN的表达是否影响宫颈癌对放射治疗的反应，以及这种膜蛋白是否可以用作宫颈癌的预后标志物。回顾性队列研究包括复旦大学附属肿瘤医院妇科肿瘤科收治的82例浸润性宫颈癌患者（上海）1991年至2000年。这些患者在根治性子宫切除术前接受A点近距离放射治疗，剂量为15戈伊。在近距离放射治疗前后，通过免疫组织化学染色检测宫颈肿瘤标本中EMMPRIN的表达，并对染色强度和染色肿瘤细胞百分比进行评分。EMMPRIN免疫反应和临床病理资料进行了分析，就生存终点使用单变量和多变量approaches.Results：EMMPRIN过度表达的频率为52.4%，在原发性宫颈癌。近距离放射治疗后EMMPRIN过表达率为13.4%，与近距离放射治疗前相比有显著性差异（P = 0.032）。EMMPRIN表达与盆腔淋巴结转移（P = 0.026）和近距离放射治疗后原发肿瘤体积缩小（P = 0.008）相关。尽管近距离放射治疗前后EMMPRIN表达与肿瘤特异性生存率无关，但通过单变量生存分析，近距离放射治疗后EMMPRIN表达增加倾向于预测不良结局（P = 0.0008）。此外，淋巴管间隙浸润、深基质浸润和淋巴结转移与不良预后显著相关。在多变量分析中，肿瘤特异性生存的独立预后因素包括近距离放射治疗后EMMPRIN表达的降低（P = 0.002;风险比0.339; 95%置信区间0.172-0.672）以及淋巴结转移（P = 0.044;风险比，2.053; 95%可信区间，1.020-4.133）。EMMPRIN的表达与近距离放射治疗后宫颈肿瘤缩小的减少有关，近距离放射治疗后EMMPRIN表达增加似乎是该患者队列生存率低的重要预测因素。我们的研究表明EMMPRIN的表达赋予对放射治疗的抵抗。因此，EMMPRIN在宫颈癌中的表达可被视为一个预后因子和治疗靶点。
Purpose: Overexpression of extracellular matrix metalloproteinase inducer (EMMPRIN), a member of the immunoglobulin family and a glycoprotein enriched on the surface of many types of tumor cells, has been reported to be linked to invasion, metastasis, growth, and survival of malignant cells. Cervical cancer, the second most prevalent cancer in women worldwide and the fifth leading cause of cancer deaths, responds to radiotherapy variably, with 30% of cases recurring after therapy. The purpose of this study was to determine whether expression of EMMPRIN affects the response of cervical cancer to radiation therapy, and whether this membrane protein can be used as a prognostic marker for cervical cancer.Experimental Design: The retrospective cohort study included 82 patients with invasive cervical cancer referred to the Department of Gynecologic Oncology at The Cancer Hospital of Fudan University (Shanghai) between 1991 and 2000. These patients were treated with brachytherapy at a dose of 15 Gy at point A before radical hysterectomy. Expression of EMMPRIN in cervical tumor specimens was examined by immunohistochemistry staining before and after brachytherapy and scored for both staining intensity and percentage of tumor cells stained. EMMPRIN immunoreactivity and clinicopathologic data were analyzed with respect to survival end points using univariate and multivariate approaches.Results: The frequency of EMMPRIN overexpression was 52.4% in primary cervical cancer. After brachytherapy, EMMPRIN overexpression was significantly reduced (13.4%) compared with corresponding tumor before brachytherapy (P = 0.032). EMMPRIN expression was associated with pelvic lymph node metastasis (P = 0.026) and reduction in primary tumor volume following brachytherapy (P = 0.008). Although EMMPRIN expression before or after brachytherapy did not correlate with tumor-specific survival, but increased expression of EMMPRIN following brachytherapy tended to predict poor outcomes by univariate survival analysis (P = 0.0008). In addition, lymph vascular space invasion, deep stromal invasion, and lymph node metastasis were significantly associated with poor prognosis. In multivariate analysis, the independent prognostic factors for tumor-specific survival included the decreased expression of EMMPRIN after brachytherapy (P = 0.002; hazard ratio, 0.339; 95% confidence interval, 0.172-0.672) as well as lymph node metastasis (P = 0.044; hazard ratio, 2.053; 95% confidence interval, 1.020-4.133).Conclusion: Expression of EMMPRIN was associated with a decrease in the reduction of cervical tumor following brachytherapy, and increased EMMPRIN expression after brachytherapy seemed to be an important predictor of poor survival in this patient cohort. Our study suggests that expression of EMMPRIN confers resistance to radiotherapy. Therefore, EMMPRIN expression in cervical cancer may be regarded both as a prognostic factor and a therapeutic target.