无特殊分子谱的子宫内膜癌(EC)(NSMP)代表了EC的最大分子类别,包含具有不同组织学和分子谱的肿瘤的混合物。这些事实可能指向不同的肿瘤生物学,临床结果,和这一分子类别内的靶向治疗反应。PIK3CA是目前唯一与EC致癌作用直接相关的可靶向激酶癌蛋白。调查一个独特的单一机构队列,我们试图根据PIK3CA致病突变的存在对NSMPECs进行分层.进一步分析了这些病例的其他已确定相关的致癌驱动基因突变。在每种情况下,组织学和临床变量也相关。总之,175个ECs由含有ARID1A的有限定制NGS面板进行了前瞻性测试,BCOR,BRCA1,BRCA2,CTNNB1,KRAS,MLH1,MSH2,MSH6,NRAS,PIK3CA,PMS2,POLD1,POLE,PTEN,和TP53基因。我们确定了80个NSMPECs组中的24个PIK3CA突变病例,与至少一个致癌驱动基因(CTNNB1,PTEN,ARID1A,KRAS,BCOR,PMS2)19例。总之,有限的NGS组可以有效地检测EC组织中特定的致病相关癌基因突变.NSMPEC类别包含30%的PIK3CA突变病例。其中,21%含有PIK3CA突变作为唯一的EC相关癌基因突变,而79%的人至少有一个突变基因。这些发现可能为未来的医疗保健计划提供信息,并提高针对PIK3CA靶向治疗的EC患者选择的有效性。
Endometrial carcinomas (EC) of no special molecular profile (NSMP) represent the largest molecular category of EC, comprising a mixture of tumors with different histology and molecular profiles. These facts likely point to different tumor biology, clinical outcomes, and targeted therapy responses within this molecular category. The PIK3CA is currently the only targetable kinase oncoprotein directly implicated in EC carcinogenesis. Investigating a unique single-institution cohort, we attempted to stratify NSMP ECs based on the presence of the PIK3CA pathogenic mutation. Those cases were further analyzed for other well-established-associated oncogenic driver gene mutations. Histological and clinical variables were also correlated in each case. Altogether, 175 ECs were prospectively tested by a limited custom NGS panel containing ARID1A, BCOR, BRCA1, BRCA2, CTNNB1, KRAS, MLH1, MSH2, MSH6, NRAS, PIK3CA, PMS2, POLD1, POLE, PTEN,and TP53 genes. We identified 24 PIK3CA mutated cases in the group of 80 NSMP ECs, with another co-occurring mutation in at least one oncogenic driver gene (CTNNB1, PTEN, ARID1A, KRAS, BCOR, PMS2) in 19 cases. In conclusion, a limited NGS panel can effectively test EC tissue for specific pathogenetically relevant oncogene mutations. The NSMP EC category contains 30% of the PIK3CA mutated cases. Of those, 21% contain the PIK3CA mutation as a sole EC-associated oncogene mutation, while 79% harbor at least one more mutated gene. These findings may inform future healthcare planning and improve the effectiveness of EC patient selection for the PIK3CA-targeted therapy.