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Article

Molecular Classification to Prognosticate Response in Medically Managed Endometrial Cancers and Endometrial Intraepithelial Neoplasia

1
Atrium Health, Division of Gynecologic Oncology, Levine Cancer Institute, Charlotte, NC 29204, USA
2
Department of Obstetrics & Gynecology, Duke University Medical Center, Durham, NC 27710, USA
3
Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710, USA
4
Duke Cancer Institute Biostatistics, Durham, NC 27710, USA
5
GCB, Department of Biostatistics & Bioinformatics, Duke University, Durham, NC 27710, USA
6
Duke Center for Genomics and Computational Biology, Durham, NC 27710, USA
7
Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Daniela M. Dinulescu
Cancers 2021, 13(11), 2847; https://doi.org/10.3390/cancers13112847
Received: 26 March 2021 / Revised: 20 May 2021 / Accepted: 28 May 2021 / Published: 7 June 2021
Uterine cancer is the most common gynecologic cancer. The treatment for women with a newly diagnosed uterine cancer is surgery to remove the uterus, fallopian tubes, ovaries, and lymph nodes. For women who desire future pregnancy or are not healthy enough to undergo surgery with hysterectomy, treatment with hormonal therapy, using the levonorgestrel intrauterine device (IUD), is an option. Response rates to this type of therapy are promising and range between 50% and 88%. This project explores a molecular classification scheme and applies it to women with uterine cancer and pre-cancer who opt for treatment with an IUD. Evaluating the genetic alterations underlying tumor development can identify patients who would be more or less likely to respond to treatment with IUDs. Additionally, this knowledge can help physicians counsel women with uterine cancer who may be interested in non-surgical options about her odds of having her cancer respond to a hormonal treatment.
Background: The aim of this study was to evaluate whether molecular classification prognosticates treatment response in women with endometrial cancers and endometrial intraepithelial neoplasia (EIN) treated with levonorgestrel intrauterine system (LNG-IUS). Methods: Patients treated with LNG-IUS for endometrial cancer or EIN from 2013 to 2018 were evaluated. Using immunohistochemistry and single gene sequencing of POLE, patients were classified into four groups as per the Proactive Molecular Risk Classifier for Endometrial cancer (ProMisE): POLE-mutated, mismatch repair-deficient (MMRd), p53 wild type (p53wt), and p53-abnormal (p53abn). Groups were assessed relative to the primary outcome of progression or receipt of definitive treatment. Results: Fifty-eight subjects with endometrioid endometrial cancer or EIN treated with LNG-IUS were included. Of these, 22 subjects (37.9%) had endometrial cancer and 36 subjects (62.1%) had EIN. Per the ProMisE algorithm, 44 patients (75.9%) were classified as p53wt, 6 (10.3%) as MMRd, 4 (6.9%) as p53abn, and 4 (6.9%) as POLE-mutated. Of the 58 patients, 11 (19.0%) progressed or opted for definitive therapy. Median time to progression or definitive therapy was 7.5 months, with p53abn tumors having the shortest time to progression or definitive therapy. Conclusions: Molecular classification of endometrial cancer and EIN prior to management with LNG-IUS is feasible and may predict patients at risk of progression. View Full-Text
Keywords: uterine cancer; endometrial cancer; levonorgestrel intrauterine device; molecular classification; mismatch repair deficiency; POLE mutation uterine cancer; endometrial cancer; levonorgestrel intrauterine device; molecular classification; mismatch repair deficiency; POLE mutation
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MDPI and ACS Style

Puechl, A.M.; Spinosa, D.; Berchuck, A.; Secord, A.A.; Drury, K.E.; Broadwater, G.; Wong, J.; Whitaker, R.; Devos, N.; Corcoran, D.L.; Strickland, K.C.; Previs, R.A. Molecular Classification to Prognosticate Response in Medically Managed Endometrial Cancers and Endometrial Intraepithelial Neoplasia. Cancers 2021, 13, 2847. https://doi.org/10.3390/cancers13112847

AMA Style

Puechl AM, Spinosa D, Berchuck A, Secord AA, Drury KE, Broadwater G, Wong J, Whitaker R, Devos N, Corcoran DL, Strickland KC, Previs RA. Molecular Classification to Prognosticate Response in Medically Managed Endometrial Cancers and Endometrial Intraepithelial Neoplasia. Cancers. 2021; 13(11):2847. https://doi.org/10.3390/cancers13112847

Chicago/Turabian Style

Puechl, Allison M., Daniel Spinosa, Andrew Berchuck, Angeles A. Secord, Kerry E. Drury, Gloria Broadwater, Janice Wong, Regina Whitaker, Nicolas Devos, David L. Corcoran, Kyle C. Strickland, and Rebecca A. Previs 2021. "Molecular Classification to Prognosticate Response in Medically Managed Endometrial Cancers and Endometrial Intraepithelial Neoplasia" Cancers 13, no. 11: 2847. https://doi.org/10.3390/cancers13112847

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