Lavage of the Uterine Cavity for Molecular Detection of Müllerian Duct Carcinomas: A Proof-of-Concept Study

子宫腔灌洗用于苗勒氏管癌的分子检测:一项概念验证研究

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作者:Elisabeth Maritschnegg, Yuxuan Wang, Nina Pecha, Reinhard Horvat, Els Van Nieuwenhuysen, Ignace Vergote, Florian Heitz, Jalid Sehouli, Isaac Kinde, Luis A Diaz Jr, Nickolas Papadopoulos, Kenneth W Kinzler, Bert Vogelstein, Paul Speiser, Robert Zeillinger

Conclusion

This study proved that tumor cells from ovarian neoplasms are shed and can be collected via lavage of the uterine cavity. Detection of OC and EC and even clinically occult OC was achieved, making it a potential tool of significant promise for early diagnosis.

Methods

Lavage of the uterine cavity was used to obtain samples from 65 patients, including 30 with OC, five with EC, three with other malignancies, and 27 with benign lesions involving gynecologic organs. These samples, as well as corresponding tumor tissue, were examined for the presence of somatic mutations using massively parallel sequencing (next-generation sequencing) and, in a subset, singleplex analysis.

Purpose

Type II ovarian cancer (OC) and endometrial cancer (EC) are generally diagnosed at an advanced stage, translating into a poor survival rate. There is increasing evidence that Müllerian duct cancers may exfoliate cells. We have established an approach for lavage of the uterine cavity to detect shed cancer cells. Patients and

Results

The lavage technique could be applied successfully, and sufficient amounts of DNA were obtained in all patients. Mutations, mainly in TP53, were identified in 18 (60%) of 30 lavage samples of patients with OC using next-generation sequencing. Singleplex analysis of mutations previously determined in corresponding tumor tissue led to further identification of six patients. Taken together, in 24 (80%) of 30 patients with OC, specific mutations could be identified. This also included one patient with occult OC. All five analyzed lavage specimens from patients with EC harbored mutations. Eight (29.6%) of 27 patients with benign lesions tested positive for mutations, six (75%) as a result of mutations in the KRAS gene.

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