p38 MAPK在不同疗程化疗后卵巢癌中的表达及临床意义

Expression and clinical significance of p38 MAPK in ovarian carcinoma of different cycles of chemotherapy

目的研究p38MAPK通路在不同化疗疗程上皮性卵巢癌中的表达及其与凋亡抑制蛋白Survivin、耐药相关蛋白(切除修复交叉互补基因1(ERCC1),肺耐药相关蛋白(LRP),谷胱甘肽转移酶(GST-π)表达的相关性及与预后的关系。方法应用免疫组织化学方法检测P-p38、Survivin、ERCC1、LRP、GST-π在29例原发性卵巢上皮癌、30例复发性卵巢上皮癌和17例经新辅助化疗后行手术的卵巢上皮癌患者治疗前后标本的表达,并进行随访。结果①P-p38在原发性卵巢癌患者中的表达与新辅助化疗术后患者中阳性表达差异无显著性(P>0.05),但明显高于复发性卵巢癌组(P<0.01);Survivin、ERCC1、GST-π在原发性卵巢癌患者中的表达与新辅助化疗术后患者中阳性表达差异无显著性(P>0.05),但明显低于复发性卵巢癌组(P<0.01)。②新辅助化疗前后的自身配对标本中P-p38、Survivin、ERCC1、LRP、GST-π蛋白的表达情况均无显著性(P>0.05)。③P-p38与Survivin、ERCC1、LRP之间存在负相关性(P<0.01),但与GST-π之间无相关性(P>0.05)。④P-p38阴性组平均生存时间短于阳性组平均生存时间,两组差异有显著性(P=0.006)。结论①多疗程化疗可能通过抑制p38 MAPK通路而提高Survivin、ERCC1、LRP的表达导致上皮性卵巢癌铂类耐药的产生,而新辅助化疗并不能导致术后耐药机会的增加。②p38MAPK通路的激活可能改善铂类耐药患者的预后。

【Objective】 To investigate the expression of p38 MAPK,Survivin,ERCC1,LRP and GST-π in ovarian carcinoma of different cycles of chemotherapy,as well as the the association between p38 MAPK with the prognosis.【Methods】 The expression of P-p38,Survivin,ERCC1,LRP and GST-π were detected using immunohistochemistry in the specimens of 29 patients with primary epithelial ovarian cancer,30 cases with recurrent epithelial ovarian cancer,and 17 patients with epithelial ovarian cancer treated with neoadjuvant chemotherapy followed by surgery.The difference of these genes＇ expression between the specimens of pre-therapy and post-therapy was also evaluated in the last group.The patients were followed up.【Results】 There was no significant difference of the expression of P-p38 between the primary ovarian cancer patients and the group after neoadjuvant chemotherapy（P 0.05）,but the expression of P-p38 in recurrent ovarian cancer group was much lower that of other two groups（P 0.01）;No significant difference of the expression of Survivin,ERCC1,GST-π was observed between the primary ovarian cancer patients and the group after neoadjuvant chemotherapy（P 0.05）,while higher expression of these genes in recurrent ovarian cancer group was detected compared to that of the other two groups（P 0.01）.The protein expression of P-p38,Survivin,ERCC1,LRP and GST-π was not statistically significant in its paired samples before and after neoadjuvant chemotherapy（P 0.05）.There was negative correlation between P-p38 and Survivin,ERCC1,LRP（P 0.01）,but not with GST-π（P 0.05）.The average survival time of P-p38-negative patients was much less than that of the positive group（P 0.01）.【Conclusions】 The multiple courses of chemotherapy may probably inhibit p38 MAPK pathway and increase the expression of Survivin,ERCC1 and LRP in epithelial ovarian cancer resulting in the resistance of platinum,which will not be affected by neoadjuvant chemotherapy.The activation of p38 MAPK may improve the prognosis of platinum-resistant patients.