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14.09.2023 | Gynecologic Oncology

Analysis of patients with endometrial carcinoma using the ProMise classifier: a pilot study from India

verfasst von: Alka Dahiya, Abarna Rajadurai, Sherin Daniel, Ajit Sebastian, Dhanya Susan Thomas, Vinotha Thomas, Rachel George, Thomas Samuel Ram, Arvind Sathyamurthy, Grace Rebekah, Abraham Peedicayil, Rekha Pai, Anitha Thomas

Erschienen in: Archives of Gynecology and Obstetrics | Ausgabe 4/2024

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Abstract

Background

Molecular subtyping of endometrial carcinomas (EC) has been shown to classify tumors into prognostically relevant groups. Characterizing EC with a limited number of markers viz., POLE mutations, p53 mutations, and MMR status, can provide valuable information.

Design

Paraffin sections of a cohort of 48 EC from a tertiary care center were characterized for the above-mentioned molecular markers and analyzed in the context of survival.

Methods

Formalin fixed paraffin embedded tissues from 48 EC were characterized for POLE mutations by Sanger sequencing (exons 9–14), for MMR (MLH1, MH2, MSH6) using immunohistochemistry (IHC) and copy number (high/low) using p53 IHC. Mutational status was integrated along with the clinicopathological details and survival analysis performed.

Results

Eleven (22.9%) patients were MMR deficient, 3 (6.3%) had POLE mutation, while 2 (4.1%) had both POLE and P53 mutations (regarded as multiple classifiers). Twelve (25%) patients were found to have P53 mutations, while the remaining 20 (41.7%) had no specific molecular profile (NSMP). Median follow-up duration was 43.5 (2–62) months with 8 recurrences and 9 deaths. Tumors with POLE mutation had the most favorable prognosis followed by the NSMP and the MMR mutated group while the P53 and multiple classifier groups had the worst prognosis in terms of OS (Log-rank p: 0.006) and PFS (Log-rank p: 0.001).

Conclusion

The integration of molecular-clinicopathologic data for endometrial cancer classification, through cost-effective, clinically applicable assays appears to be a highly objective tool that can be adopted even in resource-limited settings. It has the potential to cause a shift in the paradigm of EC pathology and management practice.

Siegel RL, Miller KD, Jemal A (2015) Cancer statistics. CA: A Cancer J Clinicians. 65(1):5–29

Consensus document for management of Uterine Cancer. Indian Council of Medical Research; 2019.

Raffone A, Travaglino A, Gabrielli O, Micheli M, Zuccalà V, Bitonti G et al (2021) Clinical features of ProMisE groups identify different phenotypes of patients with endometrial cancer. Arch Gynecol Obstet 303(6):1393–1400CrossRefPubMedPubMedCentral

Thompson EF, Huvila J, Jamieson A, Leung S, Lum A, Offman S et al (2022) Variability in endometrial carcinoma pathology practice: opportunities for improvement with molecular classification. Mod Pathol 35(12):1974–1982CrossRefPubMed

Kandoth C, McLellan MD, Vandin F, Ye K, Niu B, Lu C et al (2013) Mutational landscape and significance across 12 major cancer types. Nature 502(7471):333–339ADSCrossRefPubMedPubMedCentral

Talhouk A, McConechy MK, Leung S, Yang W, Lum A, Senz J et al (2017) Confirmation of ProMisE: a simple, genomics-based clinical classifier for endometrial cancer. Cancer 123(5):802–813CrossRefPubMed

Kommoss S, McConechy MK, Kommoss F, Leung S, Bunz A, Magrill J et al (2018) Final validation of the ProMisE molecular classifier for endometrial carcinoma in a large population-based case series. Ann Oncol 29(5):1180–1188CrossRefPubMed

Britton H, Huang L, Lum A, Leung S, Shum K, Kale M et al (2019) Molecular classification defines outcomes and opportunities in young women with endometrial carcinoma. Gynecol Oncol 153(3):487–495CrossRefPubMed

León-Castillo A, Britton H, McConechy MK, McAlpine JN, Nout R, Kommoss S et al (2020) Interpretation of somatic POLE mutations in endometrial carcinoma. J Pathol 250(3):323–335CrossRefPubMedPubMedCentral

10.

Wortman BG, Creutzberg CL, Putter H, Jürgenliemk-Schulz IM, Jobsen JJ, Lutgens LCHW et al (2018) Ten-year results of the PORTEC-2 trial for high-intermediate risk endometrial carcinoma: improving patient selection for adjuvant therapy. Br J Cancer 119(9):1067–1074CrossRefPubMedPubMedCentral

11.

Bosse T, Nout RA, McAlpine JN, McConechy MK, Britton H, Hussein YR et al (2018) Molecular classification of grade 3 endometrioid endometrial cancers identifies distinct prognostic subgroups. Am J Surg Pathol 42(5):561–568CrossRefPubMedPubMedCentral

12.

Female Genital Tumours. 5th ed. IARC; 2020. (WHO Classification of Tumours; vol. 4).

13.

Bellido F, Pineda M, Aiza G, Valdés-Mas R, Navarro M, Puente DA et al (2016) POLE and POLD1 mutations in 529 kindred with familial colorectal cancer and/or polyposis: review of reported cases and recommendations for genetic testing and surveillance. Genet Med 18(4):325–332CrossRefPubMed

14.

Burgart LJ, Chopp WV, Jain D, Bellizzi AM, Fitzgibbons PL, (2021) Template for Reporting Results of Biomarker Testing of Specimens From Patients With Carcinoma of the Colon and Rectum.

15.

Talhouk A, McConechy MK, Leung S, Li-Chang HH, Kwon JS, Melnyk N et al (2015) A clinically applicable molecular-based classification for endometrial cancers. Br J Cancer 113(2):299–310CrossRefPubMedPubMedCentral

16.

Singh N, Piskorz AM, Bosse T, Jimenez-Linan M, Rous B, Brenton JD, Gilks CB, Köbel M (2020) p53 immunohistochemistry is an accurate surrogate for TP53 mutational analysis in endometrial carcinoma biopsies. J Pathol 250(3):336–345. https://doi.org/10.1002/path.5375. (Epub 2020 Jan 29 PMID: 31829441)CrossRefPubMed

17.

Sung YN, Kim D, Kim J (2022) p53 immunostaining pattern is a useful surrogate marker for TP53 gene mutations. Diagn Pathol 17:92. https://doi.org/10.1186/s13000-022-01273-wCrossRefPubMedPubMedCentral

18.

Köbel M, Ronnett BM, Singh N, Soslow RA, Gilks CB, McCluggage WG. Interpretation of P53 Immunohistochemistry in Endometrial Carcinomas: Toward Increased Reproducibility. Int J Gynecol Pathol. 2019 Jan;38 Suppl 1(Iss 1 Suppl 1):S123-S131. doi: https://doi.org/10.1097/PGP.0000000000000488. PMID: 29517499; PMCID: PMC6127005.

19.

Stelloo E, Nout RA, Osse EM, Jürgenliemk-Schulz IJ, Jobsen JJ, Lutgens LC et al (2016) Improved risk assessment by integrating molecular and Clinicopathological factors in early-stage endometrial cancer-combined analysis of the PORTEC cohorts. Clin Cancer Res 22(16):4215–4224CrossRefPubMed

20.

Raffone A, Travaglino A, Mascolo M, Carotenuto C, Guida M, Mollo A et al (2020) Histopathological characterization of ProMisE molecular groups of endometrial cancer. Gynecol Oncol 157(1):252–259CrossRefPubMed

21.

Timmerman S, Van Rompuy AS, Van Gorp T, Vanden Bempt I, Brems H, Van Nieuwenhuysen E et al (2020) Analysis of 108 patients with endometrial carcinoma using the PROMISE classification and additional genetic analyses for MMR-D. Gynecol Oncol 157(1):245–251CrossRefPubMed

22.

Stelloo E, Bosse T, Nout RA, MacKay HJ, Church DN, Nijman HW et al (2015) Refining prognosis and identifying targetable pathways for high-risk endometrial cancer; a TransPORTEC initiative. Mod Pathol 28(6):836–844CrossRefPubMed

23.

McAlpine J, Leon-Castillo A, Bosse T (2018) The rise of a novel classification system for endometrial carcinoma; integration of molecular subclasses. J Pathol 244(5):538–549CrossRefPubMed

24.

Haruma T, Nagasaka T, Nakamura K, Haraga J, Nyuya A, Nishida T et al (2018) Clinical impact of endometrial cancer stratified by genetic mutational profiles, POLE mutation, and microsatellite instability. PLoS ONE 13(4):e0195655CrossRefPubMedPubMedCentral

25.

Jumaah AS, Al-Haddad HS, McAllister KA, Yasseen AA (2022) The clinicopathology and survival characteristics of patients with POLE proofreading mutations in endometrial carcinoma: a systematic review and meta-analysis. PLoS ONE 17(2):e0263585CrossRefPubMedPubMedCentral

26.

Nelson BH, McAlpine JN (2015) The more tumors change, the more they stay tame: do T cells keep POLE ultramutated endometrial carcinomas in check? Gynecol Oncol 138(1):1–2CrossRefPubMed

27.

Concin N, Creutzberg CL, Vergote I, Cibula D, Mirza MR, Marnitz S et al (2021) ESGO/ESTRO/ESP Guidelines for the management of patients with endometrial carcinoma. Virchows Arch 478(2):153–190CrossRefPubMed

28.

de Biase D, Maloberti T, Corradini AG, Rosini F, Grillini M, Ruscelli M, Coluccelli S, Altimari A, Gruppioni E, Sanza V, Turchetti D, Galuppi A, Ferioli M, Giunchi S, Dondi G, Tesei M, Ravegnini G, Abbati F, Rubino D, De Leo A (2023) Integrated clinicopathologic and molecular analysis of endometrial carcinoma: Prognostic impact of the new ESGO-ESTRO-ESP endometrial cancer risk classification and proposal of histopathologic algorithm for its implementation in clinical practice. Frontiers Med. https://doi.org/10.3389/fmed.2023.1146499CrossRef

29.

Ruscelli M, Maloberti T, Corradini AG, Rosini F, Querzoli G, Grillini M, Altimari A, Gruppioni E, Sanza V, Costantino A, Ciudino R, Errani M, Papapietro A, Coluccelli S, Turchetti D, Ferioli M, Giunchi S, Dondi G, Tesei M, Ravegnini G, Abbati F, Rubino D, Zamagni C, D’Angelo E, De Iaco P, Santini D, Ceccarelli C, Perrone AM, Tallini G, de Biase D, De Leo A (2023) Prognostic impact of pathologic features in molecular subgroups of endometrial carcinoma. J Pers Med 13(5):723CrossRefPubMedPubMedCentral

30.

León-Castillo A, de Boer SM, Powell ME, Mileshkin LR, Mackay HJ, Leary A, Nijman HW, Singh N, Pollock PM, Bessette P, Fyles A, Haie-Meder C, Smit VTHBM, Edmondson RJ, Putter H, Kitchener HC, Crosbie EJ, de Bruyn M, Nout RA, Horeweg N, Creutzberg CL, Bosse T (2020) TransPORTEC consortium. Molecular Classification of the PORTEC-3 Trial for High-Risk Endometrial Cancer: Impact on Prognosis and Benefit From Adjuvant Therapy. J Clin Oncol.; 38 (29) 3388–3397.

31.

van den Heerik ASVM, Horeweg N, Nout RA, Lutgens LCHW, van der Steen-Banasik EM, Westerveld GH, van den Berg HA, Slot A, Koppe FLA, Kommoss S, Mens JWM, Nowee ME, Bijmolt S, Cibula D, Stam TC, Jurgenliemk-Schulz IM, Snyers A, Hamann M, Zwanenburg AG, Coen VLMA, Vandecasteele K, Gillham C, Chargari C, Verhoeven-Adema KW, Putter H, van den Hout WB, Wortman BG, Nijman HW, Bosse T, Creutzberg CL (2020) PORTEC-4a: international randomized trial of molecular profile-based adjuvant treatment for women with high-intermediate risk endometrial cancer. Int J Gynecol Cancer 30(12):2002–2007CrossRefPubMedPubMedCentral

32.

RAINBO Research Consortium (2022) Refining adjuvant treatment in endometrial cancer based on molecular features: the RAINBO clinical trial program. Int J Gynecol Cancer 33(1):109–117CrossRefPubMedCentral

33.

Mills, Anne M. MD*; Jenkins, Taylor M. MD*; Howitt, Brooke E. MD†; Fan, Jinbo PhD, MD*; Ring, Kari L. MD‡; Cook, Ian MD‡. (2022) Mesonephric-like Endometrial Carcinoma: Results From Immunohistochemical Screening of 300 Endometrial Carcinomas and Carcinosarcomas for This Often Overlooked and Potentially Aggressive Entity. The American Journal of Surgical Pathology 46 (7) 921–932.

34.

Jamieson A, Thompson EF, Huvila J, Gilks CB, McAlpine JN (2021) p53abn Endometrial Cancer: understanding the most aggressive endometrial cancers in the era of molecular classification. Int J Gynecol Cancer 31(6):907CrossRefPubMed

Titel: Analysis of patients with endometrial carcinoma using the ProMise classifier: a pilot study from India
verfasst von: Alka Dahiya
Abarna Rajadurai
Sherin Daniel
Ajit Sebastian
Dhanya Susan Thomas
Vinotha Thomas
Rachel George
Thomas Samuel Ram
Arvind Sathyamurthy
Grace Rebekah
Abraham Peedicayil
Rekha Pai
Anitha Thomas
Publikationsdatum: 14.09.2023
Verlag: Springer Berlin Heidelberg
Erschienen in: Archives of Gynecology and Obstetrics / Ausgabe 4/2024
Print ISSN: 0932-0067
Elektronische ISSN: 1432-0711
DOI: https://doi.org/10.1007/s00404-023-07204-4

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Analysis of patients with endometrial carcinoma using the ProMise classifier: a pilot study from India