表皮生长因子受体表达与卵巢癌血管生成及化疗耐药的关系

Association of EGFR expression with angiogenesis and chemoresistance in ovarian carcinoma

目的探讨表皮牛长因子受体（EGFR）表达与卵巢癌血管生成及化疗耐药的关系。方法采用免疫组化PV-6000二步法，检测102例卵巢肿瘤组织中EGFR、肺耐药堡白（LRP）的表达和微血管密度（MVD），研究其与化疗耐药及预后的相关性。结果EGFR、LRP在恶性和交界性肿瘤中的阳性率及MVD计数均显著高于正常卵巢和良性肿瘤（P〈0.01），恶性肿瘤组织中微血管丰富。EGFR在Ⅲ-Ⅳ期、低分化和有腹水的卵巢癌中的阳性率高于I-Ⅱ期、高中分化和无腹水者（均P〈0.05），MVD计数与患者组织学分级、腹水及残留灶大小有天（P〈0.05），LRP表达与肿瘤临床病理参数无关（P〉0.05）。EGFR和LRP阳性卵巢癌患者的化疗有效率分别为57.1％和53.7％，低于EGFR和LRP阴性者（85.0％和90.9％，P〈0.05）。随访资料完整的64例患者的3年生存率为53.0％。EGFR阳性、LRP阳性、低分化、有腹水和近期化疗疗效不敏感的患者术后生存时间短（P〈0.01）。多因素分析显示，LRP表达和近期化疗疗效是影响忠者术后生存时间的独立相关因素（P〈0.05）。EGFR表达与MVD计数（r=0.548，P〈0.01）、EGFR与LRP表达（P=0.020）之间存在相关性。结论EGFR参与了卵巢癌的血管生成和化疗耐药的产生；EGFR与LRP阳性预示患者化疗敏感性低，有助于监测卵巢癌化疗耐药的产生；LRP表达和近期化疗疗效可作为卵巢癌患者的独立预后因素。

Objective To clarify the association of EGFR expression with angiogenesis and chemoresistance in ovarian cancer. Methods Immunohistochemical PV-6000 staining was used to detect the expression of EGFR, LRP protein and MVD in 102 ovarian tumor specimens. Results EGFR, LRP positive rates and MVD in borderline and malignant ovarian specimens were significantly higher than those in the normal and benign ones （P〈0.01）. EGFR positive expression rate in stage Ⅲ- Ⅳ carcinoma tissues, poor differentiation and with ascites was higher than that in stage I- Ⅱ carcinomas of well differentiation and without ascites （P 〈0.05）. MVD was related to histological grade, residual tumor and ascites, LRP positive expression had no correlation with the clinicopathologic parameters （ P 〉 0.05 ）. The effective rate of chemotherapy in patients with EGFR and LRP-positive expression were 57.1% and 53.7% , respectively, significantly lower than that in cases with EGFR and LRP-negative expression （85.0% and 90.9%, P 〈 0.05）. In the 64 cases with complete data, the three-year survival rate was 53.0%. The survival time was shorter in the cases with EGFR and LRP-positive expression, poor differentiation, ascites and chemoresistance （P〈0.01）, and only LRP-positive expression and chemotherapeutic effect were independently related to survival time （P〈0.05）. There was a correlation between EGFR and MVD （r=0.548,P〈0.01）, EGFR and LRP positive expression （P=0.020）. Conclusion The expression of EGFR in ovarian cancer is related to angiogenesis and chemoresistance. EGFR and LRP-positive expression are related to chemoresistance, and detection of the two proteins may be helpful in guiding chemotherapy choice for ovarian cancer, LRP-positive expression and chemotherapeutic effect may be independent prognostic factors.