朊蛋白与p53突变在卵巢浆液性癌组织中表达的相关性及预后意义

Correlation and prognostic significance of expression of prion protein and p53 mutation in ovarian serous carcinoma

目的:探讨卵巢浆液性癌组织中朊蛋白表达水平及其与p53突变的相关性。方法:选取2012年11月10日至2019年10月30日北京大学第三医院妇产科收治的Ⅰ~Ⅳ期卵巢浆液性癌139例,同时选取20例正常卵巢组织、20例卵巢良性肿瘤组织作为对照。免疫组化、p53突变测序法检测朊蛋白表达水平及p53突变类型。结果:朊蛋白在卵巢浆液性癌组织中阳性表达率明显高于卵巢良性肿瘤组织和正常卵巢组织,差异均有统计学意义(59%vs 30%、20%,P分别为0.034、0.003)。卵巢浆液性癌中p53突变率高达84.89%(118/139),主要位于第5外显子(29.66%,35/118)以及DNA结合域的热点突变位点(50.84%,60/118);朊蛋白高表达组中p53构象突变率为71.93%(41/57),显著高于朊蛋白低表达组(45.90%,28/61),差异有统计学意义(P=0.004)。p53构象突变与卵巢浆液性癌淋巴结转移(P=0.005)及耐药(P=0.009)密切相关。p53构象突变患者的平均疾病无进展生存期[(34.99±2.72)月vs(43.01±2.35)月,P=0.036]及平均总生存期[(47.94±3.40)月vs(56.00±2.89)月,P=0.049]均低于p53接触突变患者。结论:卵巢浆液性癌组织中朊蛋白呈高表达,并与p53构象突变相关。p53构象突变与卵巢浆液性癌不良预后相关。

Objective:To investigate the expression levels of prion protein in ovarian serous carcinoma and to analyze the relationship between prion protein expression levels and p53 mutations.Methods:A total of 139 cases of stageⅠ~Ⅳovarian serous carcinoma between November 10,2012,and October 30,2019,were selected.Additionally,20 cases of normal ovarian tissue and 20 cases of benign ovarian tumors were selected as controls.Immunohistochemistry and p53 mutation sequencing methods were used to detect prion protein expression levels and p53 mutation types.Results:The positive rate of prion protein in ovarian serous carcinoma was significantly higher than that in benign ovarian tumor tissues(59%vs 30%,P=0.034)and normal ovarian tissues(59%vs 20%,P=0.003).In ovarian serous carcinoma,the p53 mutation rate was as high as 84.89%(118/139),mainly located in exon 5(29.66%,35/118)and the hotspot mutation sites of the DNA-binding domain(50.84%,60/118).In the prion protein high-expression group,the p53 conformational mutation rate was 71.93%(41/57),significantly higher than that in the prion protein low-expression group(45.90%,28/61),with a statistically significant difference(P=0.004).p53 conformational mutations were closely related to lymph node metastasis(P=0.005)and drug resistance(P=0.009)in ovarian serous carcinoma.The average progression-free survival[(34.99±2.72)months vs(43.01±2.35)months,P=0.036]and average overall survival[(47.94±3.40)months vs(56.00±2.89)months,P=0.049]were lower in patients with p53 conformational mutations than those with p53 contact mutations.Conclusion:Prion protein is highly expressed in ovarian serous carcinoma and is associated with p53 conformational mutations.p53 conformational mutations are related to poor prognosis in ovarian serous carcinoma.