Skip to main content

Molecular Pathology of Endometrial Tumors

  • Chapter
  • First Online:
Molecular Surgical Pathology

Abstract

In the Western world, endometrial carcinoma is the most common malignant tumor of the female genital tract. The annual incidence has been estimated at 10–20 per 100,000 women. Several histologic types are recognized: the estrogen-related (type I, endometrioid) and the nonestrogen-related (type II, serous), being the two most frequent of them. The clinicopathological differences are paralleled by specific genetic alterations, with endometrioid carcinoma showing microsatellite instability and mutations in PTEN, PIK3CA, KRAS, and CTNNB1 (b-catenin), and serous carcinoma exhibiting TP53 mutations and chromosomal instability. Women with hereditary nonpolyposis colorectal carcinoma (HNPCC) have germline mutations in one of the DNA mismatch repair genes and frequently develop endometrioid endometrial carcinomas. Some nonendometrioid carcinomas probably arise from preexisting endometrioid carcinomas because of tumor progression and, not surprisingly, some tumors exhibit combined or mixed features at the clinical, pathological, and molecular levels. The TCGA-based molecular classification has emerged as a good tool for stratifying patients according to prognosis. Four groups were identified: (1) Ultramutated (POLE-mutated), (2) Tumors with microsatellite instability/mismatch repair deficiency, (3) Low copy number tumors/Tumors with nonspecific molecular profile, and (4) High copy number tumors. A TCGA-based surrogate has been developed to bring that molecular classification into clinical practice. There are several promising targeted therapies, including c-erbB2 and immune checkpoint inhibitors.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 119.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Similar content being viewed by others

Further Reading

  • Buza N, Roque DM, Santin AD. HER2/neu in endometrial cancer: a promising therapeutic target with diagnostic challenges. Arch Pathol Lab Med. 2014;138(3):343–50.

    Article  PubMed  Google Scholar 

  • Cho KR, Cooper K, Croce S, Djordevic B, Herrington S, Howitt B, et al. International Society of Gynecological Pathologists (ISGyP) endometrial cancer project: guidelines from the special techniques and ancillary studies group. Int J Gynecol Pathol. 2019;38(Suppl 1):S114–22.

    Article  PubMed  Google Scholar 

  • Concin N, Creutzberg CL, Vergote I, Cibula D, Mirza MR, Marnitz S, et al. ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma. Virchows Arch. 2021;478(2):153–90.

    Article  PubMed  Google Scholar 

  • Costas L, Frias-Gomez J, Guardiola M, Benavente Y, Pineda M, Pavón M, et al. New perspectives on screening and early detection of endometrial cancer. Int J Cancer. 2019;145(12):3194–206.

    Article  CAS  PubMed  Google Scholar 

  • de Boer SM, Powell ME, Mileshkin L, Katsaros D, Bessette P, Haie-Meder C, et al. Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): final results of an international, open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2018;19(3):295–309.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kandoth C, Schultz N, Cherniack AD, Akbani R, Liu Y, Shen H, et al. Integrated genomic characterization of endometrial carcinoma. Nature. 2013;497(7447):67–73.

    Article  PubMed  Google Scholar 

  • León-Castillo A, de Boer SM, Powell ME, Mileshkin LR, Mackay HJ, Leary A, et al. Molecular classification of the PORTEC-3 trial for high-risk endometrial cancer: impact on prognosis and benefit from adjuvant therapy. J Clin Oncol. 2020;38(29):3388–97.

    Article  PubMed  PubMed Central  Google Scholar 

  • Makker V, Taylor MH, Aghajanian C, Oaknin A, Mier J, Cohn AL, et al. Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer. J Clin Oncol. 2020;38(26):2981–92.

    Article  PubMed  PubMed Central  Google Scholar 

  • Megino-Luque C, Moiola CP, Molins-Escuder C, López-Gil C, Gil-Moreno A, Matias-Guiu X, et al. Small-molecule inhibitors (SMIs) as an effective therapeutic strategy for endometrial cancer. Cancers (Basel). 2020;12(10):2751.

    Article  CAS  PubMed  Google Scholar 

  • Murali R, Davidson B, Fadare O, Carlson JA, Crum CP, Gilks CB, et al. High-grade endometrial carcinomas: morphologic and Immunohistochemical features, diagnostic challenges and recommendations. Int J Gynecol Pathol. 2019;38(Suppl 1):S40–63.

    Article  PubMed  Google Scholar 

  • Oaknin A, Tinker AV, Gilbert L, Samouëlian V, Mathews C, Brown J, et al. Clinical activity and safety of the anti-programmed death 1 monoclonal antibody dostarlimab for patients with recurrent or advanced mismatch repair-deficient endometrial cancer: a nonrandomized phase 1 clinical trial. JAMA Oncol. 2020;6(11):1766–72.

    Article  PubMed  Google Scholar 

  • Piulats JM, Guerra E, Gil-Martín M, Roman-Canal B, Gatius S, Sanz-Pamplona R, et al. Molecular approaches for classifying endometrial carcinoma. Gynecol Oncol. 2017;145(1):200–7.

    Article  CAS  PubMed  Google Scholar 

  • Soslow RA, Tornos C, Park KJ, Malpica A, Matias-Guiu X, Oliva E, et al. Endometrial carcinoma diagnosis: use of FIGO grading and genomic subcategories in clinical practice: recommendations of the International Society of Gynecological Pathologists. Int J Gynecol Pathol. 2019;38(Suppl 1):S64–74.

    Article  PubMed  Google Scholar 

  • WHO. Female genital tumours. WHO classification of tumours, vol. 4. 5th ed. Lyon: Editorial World Health Organization; 2020.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Xavier Matias-Guiu .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Gatius, S., Eritja, N., Matias-Guiu, X. (2023). Molecular Pathology of Endometrial Tumors. In: Cheng, L., Netto, G.J., Eble, J.N. (eds) Molecular Surgical Pathology. Springer, Cham. https://doi.org/10.1007/978-3-031-35118-1_12

Download citation

  • DOI: https://doi.org/10.1007/978-3-031-35118-1_12

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-031-35117-4

  • Online ISBN: 978-3-031-35118-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics