HSP70、突变型P53在复发性、耐药性卵巢癌中的表达及临床意义

目的:探讨卵巢初治和复发上皮癌组织中热休克蛋白70(HSP70)与突变型P53(mtP53)的表达情况及其在临床应用E1B-55KD缺陷型腺病毒联合化疗治疗卵巢癌中的意义,探索一种新的治疗方法。方法:采用免疫组化方法测定卵巢肿瘤组织中HSP70与mtP53的表达情况。同时用Western blot法测定卵巢癌患者血浆中HSP70在手术和化疗前后的表达情况。结果:卵巢癌组织中,复发性卵巢癌HSP70、mtP53阳性率明显高于初治卵巢癌(P<0.05);HSP70和mtP53的阳性强度在进展期、低分化卵巢癌中明显高于早期、高分化卵巢癌(P<0.05)。卵巢癌中HSP70和mtP53共同阳性率为55.9%(33/59);其中复发癌组织中,HSP70和mtP53共同阳性率明显高于初治癌。复发卵巢癌中,铂类耐药型卵巢癌HSP70、mtP53阳性率明显高于非耐药组(P<0.05)。血浆中HSP70在手术后第2～4天及化疗后第2天明显增高,术后第6天及化疗后第4天恢复原水平。结论:HSP70与mtP53在复发、耐药性卵巢癌中的高表达,使溶瘤性腺病毒的应用成为可能,腺病毒应用时机选择在手术或化疗后2 d之内可能效果更佳。

Expression and Clinical Value of mtP53 and HSP70 in Recurrent Drug Resistance in Ovarian Cancer

Objective： To examine the expression of HSP70 and mutant type P53 in patients with princeps and recurrent epithelial ovarian cancer and to discuss the clinical value of them in use of E1B-55KD deleted adenovirus plus cisplatin-based chemotherapy on patients with epithelial ovarian carcinoma.Method： Expression of mtP53 and HSP70 in varian tumor tissues was evaluated by immunohistochemical method.Expression of HSP70 in plasma for patients with epithelial ovarian cancer was studied by western blot method to compare the intensity before and after operation and chemotherapy.Results： The positive rate of HSP70 expression in recurrent cancer was significantly higher than that in primary cancer in varian tumor tissues（P〈0.05）;The positivity was significantly higher in advanced-stage and low grade cancer than in early-stage and high grade invasive cancer（P〈0.05）.Furthermore,there was significant correlation between mtP53 positivity and the expression of HSP70.In ovarian cancer,the rate of mtP53 positivity with HSP70 positivity was 55.9%（33/59）.In recurrent ovarian cancer,the rate of mtP53 positivity with HSP70 positivity was significantly higher than in primary cancer.HSP70 positivity and P53 positivity were significantly higher in cisplatin-resist ovarian cancer than non cisplatin-resist cancer（P〈0.05）.Expression of hsp70 in the plasma was significantly higher after surgery 2~4 days and chemotherapy 2 days.After surgery 6 days and chemotherapy 4 days,the level of HSP70 comebacked the normal.Conclusion： Higher expression of hsp70 and mtP53 in the princeps and recurrent epithelial ovarian cancer makes it possible to apply replication-selective oncolytic adenoviruses.E1B-deleted adenovirus plus cisplatin-based chemotherapy is significantly effective and optimal within 2 days after surgery and chemotherapy.