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Towards less invasive molecular diagnostics for endometrial cancer: massively parallel sequencing of endometrial lavage specimens in women attending for an office hysteroscopy

Abstract

We aimed to detect endometrial cancer (EC)–associated mutations in endometrial lavage specimens collected in an office setting and to compare the detected mutations with those identified in tissue samples. Participants included 16 women attending for an office hysteroscopy because of suspected EC between July 2020 and October 2021. Massively parallel sequencing was conducted using the targeted 72 cancer-associated genes. Endometrial lavage specimens, endometrial tissue samples, and blood samples were simultaneously sequenced to establish the concordance of genetic alterations. In this study, the vast majority of EC-associated mutations identified in lavage samples (R2 = 0.948) were identical to those detected in endometrial tissues. Of the 13 patients with EC, 12 (92.3%) had at least one mutation identified in endometrial lavage samples. Notably, no mutations in lavage samples were identified in the two patients with a previous history of EC but no actual endometrial lesions, supporting a high negative predictive value of the test. A patient previously diagnosed with EC and with current evidence of atypical hyperplasia showed persisting PTEN, PIK3R1, and KRAS mutations in her endometrial lavage specimen. PTEN was the most commonly mutated gene, followed by PIK3R1, ARID1A, PIK3CA, CTNNB1, and KRAS. In conclusions, our study provides pilot evidence on the actionability of uterine lavage samples sequencing to detect EC-associated mutations in women with suspected endometrial lesions. In a precision medicine framework, the high mutational concordance between uterine lavage samples and tissue specimens may help inform less invasive diagnostic protocols and the need for ongoing surveillance in patients with EC who wished for fertility-preserving treatment.

Key messages

• Sequencing of uterine lavage samples collected by office hysteroscopy is feasible.

• Most EC mutations identified in lavage were identical to endometrial tissues.

• Sequencing of uterine lavage samples may help inform diagnostic protocols for EC.

• This approach can be used for recurrence surveillance in patients with EC.

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Data availability

All data generated or analyzed during this study are included in this published article and its supplementary information files.

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Acknowledgements

We thank Ms Jung-Erh Yang and Chu-Chun Huang for excellent technical assistance.

Funding

This work was supported by the Taiwan Ministry of Science and Technology (grant number 110–2314-B-182A-027-MY3 to AC, MOST108-2320-B-182–036-MY3 to RCW) and the Chang Gung Medical Foundation (grant numbers CIRPG 3 K0031/2 to AC and 3 J1302/3, CMRPG3H1153 to RCW).

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Authors

Contributions

A.C. and R.C.W.: study concept and design. K.Y.W., C.H.W., Y.S.L., Y.S.T., H.J.H., C.H.L., T.C.C., and A.S.C.: data collection and interpretation. R.C.W.: pathological examinations. A.C. C.Y.L., and R.C.W.: manuscript drafting. A.C. and R.C.W.: critical revision of the manuscript for impact intellectual content. The manuscript has been read and approved by all authors.

Corresponding author

Correspondence to Ren-Chin Wu.

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Ethical approval

The Institutional Review Board approval of the Chang Gung Memorial Hospital (identifier: 202001329B0) granted ethical approval to process and analyze all clinical/demographic data and biological samples. Written informed consent was obtained from the patients.

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The authors declare no competing interests.

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Chao, A., Wu, KY., Lin, CY. et al. Towards less invasive molecular diagnostics for endometrial cancer: massively parallel sequencing of endometrial lavage specimens in women attending for an office hysteroscopy. J Mol Med 100, 1331–1339 (2022). https://doi.org/10.1007/s00109-022-02239-7

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  • DOI: https://doi.org/10.1007/s00109-022-02239-7

Keywords

  • Endometrial cancer
  • Uterine lavage
  • Biopsy
  • Diagnostics
  • Surveillance