复发性“超低危”子宫内膜癌的临床特征和基因组分析。
Clinical patterns and genomic profiling of recurrent 'ultra-low risk' endometrial cancer.
机构信息
Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
出版信息
Int J Gynecol Cancer. 2020 Jun;30(6):717-723. doi: 10.1136/ijgc-2020-001241. Epub 2020 May 5.
OBJECTIVE
Despite good prognosis for patients with low-risk endometrial cancer, a small subset of women with low-grade/low-stage endometrial cancer experience disease recurrence and death. The aim of this study was to characterize clinical features and mutational profiles of recurrent, low-grade, non-myoinvasive, 'ultra-low risk' endometrioid endometrial adenocarcinomas.
METHODS
We retrospectively identified patients with International Federation of Gynecology and Obstetrics (FIGO) stage IA endometrioid endometrial cancers who underwent primary surgery at our institution, between January 2009 and February 2017, with follow-up of ≥12 months. 'Ultra-low risk' was defined as FIGO tumor grade 1, non-myoinvasive, and lacking lymphovascular space invasion. Tumor-normal profiling using massively parallel sequencing targeting 468 genes was performed. Microsatellite instability was assessed using MSIsensor. DNA mismatch repair (MMR) protein proficiency was determined by immunohistochemistry.
RESULTS
A total of 486 patients with ultra-low risk endometrioid endometrial cancers were identified: 14 (2.9%) of 486 patients developed a recurrence. Median follow-up for non-recurrent endometrioid endometrial cancers: 34 (range 12-116) months; for recurrent endometrioid endometrial cancers: 50.5 (range 20-116) months. Patients with recurrent disease were older, had lower body mass index, and were most commonly non-White (p=0.025, p<0.001, and p<0.001, respectively). Other clinical characteristics did not differ. MMR immunohistochemistry was obtained for 211 (43%) tumors: 158 (75%) MMR-proficient and 53 (25%) MMR-deficient. Primary tumors of 9 recurrent and 27 non-recurrent endometrioid endometrial cancers underwent mutational profiling. Most were microsatellite stable (6/9, 67% recurrent; 25/27, 93% non-recurrent). Recurrent and mutations were present in both groups. Exon 3 hotspot mutations were found in 4/9 (44%) recurrent and 8/27 (30%) non-recurrent (p=0.44).
CONCLUSIONS
Patients diagnosed with ultra-low risk endometrioid endometrial cancers have an overall excellent prognosis. However, in our study, 2.9% of patients with no identifiable clinical or pathologic risk factors developed recurrence. Further work is warranted to elucidate the mechanism for recurrence in this population.
目的
尽管低危子宫内膜癌患者的预后良好，但一小部分低级别/低分期子宫内膜癌患者仍会出现疾病复发和死亡。本研究旨在描述复发、低级别、非肌层浸润、“超低风险”子宫内膜样腺癌的临床特征和突变谱。
方法
我们回顾性地确定了在我院接受治疗的国际妇产科联合会（FIGO）IA 期子宫内膜样子宫内膜癌患者，这些患者于 2009 年 1 月至 2017 年 2 月间进行了初次手术，随访时间≥12 个月。“超低风险”定义为 FIGO 肿瘤分级 1 级、非肌层浸润且无脉管侵犯。使用靶向 468 个基因的大规模平行测序对肿瘤-正常样本进行分析。使用 MSIsensor 评估微卫星不稳定性。通过免疫组化测定 DNA 错配修复（MMR）蛋白功能。
结果
共确定了 486 例超低风险子宫内膜样腺癌患者：486 例患者中 14 例（2.9%）发生了复发。非复发子宫内膜样腺癌患者的中位随访时间为 34（范围 12-116）个月；复发子宫内膜样腺癌患者为 50.5（范围 20-116）个月。复发患者年龄较大，体重指数较低，且多为非白人（p=0.025，p<0.001 和 p<0.001）。其他临床特征无差异。对 211 例（43%）肿瘤进行了 MMR 免疫组化检测：158 例（75%）MMR 功能正常，53 例（25%）MMR 功能缺失。对 9 例复发和 27 例非复发子宫内膜样腺癌的原发性肿瘤进行了突变分析。大多数为微卫星稳定（6/9，67%复发；25/27，93%非复发）。在这两组中都发现了 和 突变。9 例复发肿瘤中有 4 例（44%）和 27 例非复发肿瘤中有 8 例（30%）存在外显子 3 热点突变（p=0.44）。
结论
诊断为超低风险子宫内膜样腺癌的患者总体预后良好。然而，在我们的研究中，2.9%的患者无明显临床或病理危险因素，但出现了复发。需要进一步研究以阐明该人群中复发的机制。
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