【作者】 刘佳；

【导师】 魏军成；

【作者基本信息】 华中科技大学 ， 妇产科学（专业学位）， 2023， 硕士

【摘要】 目的:探究黄素化卵泡膜瘤伴硬化性腹膜炎(Luteinized Thecoma Associated with Sclerosing Peritonitis,LTSP)与卵泡膜细胞瘤非特指型(Thecoma Not Otherwise Specified,Thecoma NOS)之间具有病理鉴别意义的临床分子病理标记物,帮助临床医师快速准确地做出诊断并针对性地制定后续治疗策略。方法:本研究为多中心回顾性病例对照研究,纳入湖北省四家医疗机构自2001年1月至2020年12月期间诊断为LTSP或Thecoma NOS的患者。所有患者的石蜡包埋组织样本均采用免疫组织化学染色法进行分子病理标记物检测,共纳入10个分子病理标记物:α-1,6-甘露糖蛋白6-β-N-乙酰氨基葡萄糖转移酶B(Alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase B,MGAT5B)、核受体协同激活因子 3(Nuclear Receptor Coactivator 3,NCOA3)、增殖标记蛋白 Ki-67(Proliferation Marker Protein Ki-67,MKI67)、雌激素受体(Estrogen Receptor,ESR)、孕激素受体(Progesterone Receptor,PGR)、波形蛋白(Vimentin,VIM)、受体酪氨酸蛋白激酶 erbB-2(Receptor Tyrosine-Protein Kinase erbB-2,HER2)、连环蛋白 β-1(Cateninbeta-1,β-Catenin)、分化抗原簇 99(CD99 antigen,CD99)和肾母细胞瘤蛋白(Wilms Tumor Protein,WT1)。此外,本研究采用全外显子测序和荧光原位杂交实验检测MGAT5B-NCOA3融合基因。数据的统计分析采用独立样本T检验、单因素方差分析和事后多重比较方法。结果:本研究共纳入102名患者,包括11名LTSP确诊患者和91名Thecoma NOS确诊患者。相较于Thecoma NOS,在LTSP确诊患者石蜡包埋组织样本中,MGAT5B(P<0.001)、NCOA3(P<0.001)、MKI67(P<0.001)和β-Catenin(P<0.001)表达水平更高,CD99(P=0.013)和WT1(P<0.001)表达水平更低,均具有统计学意义。此外,在LTSP组织样本中首次发现MGAT5B-NCOA3融合基因,其表达水平相较于Thecoma NOS和阴性对照更高,具有统计学意义(P<0.001)。结论:相较于Thecoma NOS,LTSP表达更高水平的MGAT5B、NCOA3、MKI67和β-Catenin分子病理标记物和更低水平的CD99和WT1分子病理标记物。此外,LTSP高水平表达MGAT5B-NCOA3融合基因。本研究结果有助于临床医师对LTSP和Thecoma NOS进行病理鉴别,并对LTSP的潜在发病机制提供了新的方向。更多还原

【Abstract】 Objective:To explore the discriminative clinical molecular pathological markers between luteinized thecoma associated with sclerosing peritonitis(LTSP)and thecoma not otherwise specified(Thecoma NOS),so as to help clinicians diagnose and treat accurately.Methods:As a multicenter retrospective case-control study,four hospitals in Hubei Province were incorporated in this study,with patients diagnosed with LTSP or Thecoma NOS from January 2001 to January 2020.The expression of ten selected molecular pathological markers were analyzed by immunohistochemistry,containing alpha-1,6mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase B(MGAT5B),nuclear receptor coactivator 3(NCOA3),proliferation marker protein Ki-67(MKI67),estrogen receptor(ESR),progesterone receptor(PGR),Vimentin(VIM),receptor tyrosine-protein kinase erbB-2(HER2),Catenin beta-1(β-Catenin),CD99 antigen(CD99)and Wilms tumor protein(WT1).Furthermore,Whole-exome sequencing and fluorescence in situ hybridization were used to examine the MGAT5B-NCOA3 fusion gene.Statistical analysis was performed using independent t-test,one-way analysis of variance test and post hoc test.Results:102 patients were included in this study,containing 11 cases with LTSP and 91 cases with Thecoma NOS.Six significant markers were verified for the discrimination between LTSP and Thecoma NOS,containing four up-regulating indicators MGAT5B(P<0.001),NCOA3(P<0.001),MKI67(P<0.001)and β-Catenin(P<0.001)and two downregulating markers CD99(P=0.013)and WT1(P<0.001)in luteinized cells.In addition,the MGAT5B-NCOA3 fusion gene was identified in LTSP for the first time with significant rich expression compared to Thecoma NOS and control group(P<0.001).Conclusions:Six significant molecular pathological markers were verified in LTSP and Thecoma NOS,with significant high expression of MGAT5B,NCOA3,MKI67 and βCatenin and significant low expression of CD99 and WT1 in LTSP.Besides,a firstdiscovered MGAT5B-NCOA3 fusion gene was highly expressed in LTSP.This work could help clinicians to discriminate LTSP and Thecoma NOS pathologically and provide a new direction for the potential pathogenesis of LTSP.更多还原