Mota Alba, Colás Eva, García-Sanz Pablo, Campoy Irene, Rojo-Sebastián Alejandro, Gatius Sonia, García Ángel, Chiva Luis, Alonso Sonsoles, Gil-Moreno Antonio, González-Tallada Xavier, Díaz-Feijoo Berta, Vidal August, Ziober-Malinowska Patrycja, Bobiński Marcin, López-López Rafael, Abal Miguel, Reventós Jaume, Matias-Guiu Xavier, Moreno-Bueno Gema
Departamento de Bioquímica, Universidad Autónoma de Madrid (UAM), Instituto de Investigaciones Biomédicas 'Alberto Sols' (CSIC-UAM), IdiPAZ, Madrid, Spain.
MD Anderson International Foundation, Madrid, Spain.
Mod Pathol. 2017 Jan;30(1):134-145. doi: 10.1038/modpathol.2016.143. Epub 2016 Sep 2.
Endometrial cancer is the most common cancer of the female genital tract in developed countries. Although the majority of endometrial cancers are diagnosed at early stages and the 5-year overall survival is around 80%, early detection of these tumors is crucial to improve the survival of patients given that the advanced tumors are associated with a poor outcome. Furthermore, correct assessment of the pre-clinical diagnosis is decisive to guide the surgical treatment and management of the patient. In this sense, the potential of targeted genetic sequencing of uterine aspirates has been assessed as a pre-operative tool to obtain reliable information regarding the mutational profile of a given tumor, even in samples that are not histologically classifiable. A total of 83 paired samples were sequenced (uterine aspirates and hysterectomy specimens), including 62 endometrioid and non-endometrioid tumors, 10 cases of atypical hyperplasia and 11 non-cancerous endometrial disorders. Even though diagnosing endometrial cancer based exclusively on genetic alterations is currently unfeasible, mutations were mainly found in uterine aspirates from malignant disorders, suggesting its potential in the near future for supporting the standard histologic diagnosis. Moreover, this approach provides the first evidence of the high intra-tumor genetic heterogeneity associated with endometrial cancer, evident when multiple regions of tumors are analyzed from an individual hysterectomy. Notably, the genetic analysis of uterine aspirates captures this heterogeneity, solving the potential problem of incomplete genetic characterization when a single tumor biopsy is analyzed.
子宫内膜癌是发达国家女性生殖道最常见的癌症。尽管大多数子宫内膜癌在早期被诊断出来，5年总生存率约为80%，但鉴于晚期肿瘤预后较差，早期发现这些肿瘤对于提高患者生存率至关重要。此外，正确评估临床前诊断对于指导患者的手术治疗和管理具有决定性意义。从这个意义上讲，子宫吸出物的靶向基因测序作为一种术前工具的潜力已得到评估，以获取有关特定肿瘤突变谱的可靠信息，即使是在组织学上无法分类的样本中。总共对83对样本（子宫吸出物和子宫切除标本）进行了测序，包括62例子宫内膜样和非子宫内膜样肿瘤、10例非典型增生和11例非癌性子宫内膜疾病。尽管目前仅基于基因改变诊断子宫内膜癌是不可行的，但突变主要在恶性疾病的子宫吸出物中发现，这表明其在不久的将来支持标准组织学诊断的潜力。此外，这种方法首次证明了与子宫内膜癌相关的肿瘤内高度基因异质性，当从单个子宫切除标本中分析肿瘤的多个区域时很明显。值得注意的是，子宫吸出物的基因分析捕捉到了这种异质性，解决了分析单个肿瘤活检时基因特征不完整的潜在问题。
