Weng Cindy Hsuan, Wu Kai-Yun, Wang Chin-Jung, Huang Huei-Jean, Tsai Chia-Lung, Lin Chiao-Yun, Ro Aileen, Lai Chyong-Huey, Chao An-Shine, Wu Ren-Chin, Chao Angel
Department of Obstetrics and Gynecology, Linkou Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan.
Gynecologic Cancer Research Center, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Front Med (Lausanne). 2022 Dec 22;9:1090788. doi: 10.3389/fmed.2022.1090788. eCollection 2022.
Endometrial hyperplasia (EH), particularly with atypia, is considered an antecedent of endometrial adenocarcinoma. In this study, we aimed to apply massively parallel sequencing of endometrial lavage specimens for the detection of cancer-associated mutations in atypical (AEH) and non-atypical endometrial hyperplasia (NEH). The identified alterations were compared with those detected in tissue samples.
Endometrial lavage specimens and parallel biopsy samples ( = 11 for AEH and = 9 for NEH) were obtained from 18 women (9 with AEH and 9 with NEH) who received an office hysteroscopy for suspected endometrial lesions. All samples were tested for somatic mutations in hotspot regions of 72 cancer-associated genes by massively parallel sequencing.
On analyzing sequencing data, the presence of at least one cancer-associated gene mutation was identified in 72.7 and 44.4% of endometrial lavage specimens obtained from women with AEH and NEH, respectively ( = 0.362, 95% confidence interval = 0.72-3.70). The concordance rates between mutations identified in endometrial lavage specimens and endometrial biopsies were 54.5 and 0% from women with AEH and NEH, respectively ( = 0.014). A patient with NEH harbored mutations in endometrial lavage with the same mutations found in the tissue specimen at low allele frequency below detection cutoff, raising the suspicion of missed focal atypia.
Endometrial hyperplasia is characterized by a high burden of cancer-associated mutations, particularly in the presence of atypia. Our study, albeit performed with a relatively small number of samples, indicates that their detection by massively parallel sequencing of endometrial lavage is feasible. Our findings may allow tailoring of endometrial biopsies to the individual risk of AEH; additionally, they can pave the way toward less invasive surveillance protocols in patients with known EH.
子宫内膜增生（EH），尤其是伴有异型性的增生，被认为是子宫内膜腺癌的前驱病变。在本研究中，我们旨在应用子宫内膜灌洗标本的大规模平行测序来检测非典型（AEH）和非非典型子宫内膜增生（NEH）中与癌症相关的突变。将鉴定出的改变与在组织样本中检测到的改变进行比较。
从18名因疑似子宫内膜病变接受门诊宫腔镜检查的女性中获取子宫内膜灌洗标本和平行活检样本（AEH患者11例，NEH患者9例）。通过大规模平行测序对所有样本的72个与癌症相关基因的热点区域进行体细胞突变检测。
分析测序数据时，分别在72.7%的AEH女性和44.4%的NEH女性的子宫内膜灌洗标本中鉴定出至少一种与癌症相关的基因突变（P = 0.362，95%置信区间 = 0.72 - 3.70）。AEH和NEH女性的子宫内膜灌洗标本与子宫内膜活检中鉴定出的突变的一致性率分别为54.5%和0%（P = 0.014）。一名NEH患者的子宫内膜灌洗中有突变，在组织标本中以低于检测阈值的低等位基因频率发现了相同的突变，这增加了漏诊局灶性异型性的怀疑。
子宫内膜增生的特征是与癌症相关的突变负担较高，尤其是在存在异型性的情况下。我们的研究虽然样本数量相对较少，但表明通过子宫内膜灌洗的大规模平行测序检测这些突变是可行的。我们的发现可能有助于根据个体患AEH的风险定制子宫内膜活检；此外，它们可以为已知EH患者采用侵入性较小的监测方案铺平道路。
