DNA mismatch repair-deficient endometrial carcinosarcomas portend distinct clinical, morphologic, and molecular features compared with traditional carcinosarcomas Journal Article

   


Authors: Segura, S. E.; Pedra Nobre, S.; Hussein, Y. R.; Abu-Rustum, N. R.; Weigelt, B.; Soslow, R. A.; DeLair, D. F.
Article Title: DNA mismatch repair-deficient endometrial carcinosarcomas portend distinct clinical, morphologic, and molecular features compared with traditional carcinosarcomas
Abstract: Uterine carcinosarcomas (UCSs) are aggressive neoplasms composed of high-grade malignant epithelial and mesenchymal elements with most (∼90%) showing TP53 abnormalities. A subset, however, shows mismatch repair deficiency (MMR-D). We sought to describe their clinical, morphologic, and molecular features. Clinicopathologic data of MMR-D UCSs were recorded including age, stage, follow-up, mismatch repair and p53 immunohistochemistry (IHC), MLH1 promoter methylation status, and germline alterations, TP53 mutation status, microsatellite instability and mutational burden by massively parallel sequencing. Seventeen (6.2%) MMR-D were identified among 276 UCSs. Of MMR-D UCSs, the median age was 60 years. mismatch repair IHC loss is as follows: MLH1/PMS2 65%, MSH2/MSH6 18%, MSH6 12%, and PMS2 6%. MLH1 promoter methylation and Lynch syndrome was identified in 47% and 12% of cases, respectively. Cases with p53 IHC showed the following patterns: wild-type 70%, aberrant 20%, and equivocal 10%. Of cases with sequencing, 88% were hypermutated and microsatellite instability high. High-grade endometrioid, undifferentiated, and clear cell carcinoma was present in 53%, 41%, and 6% of cases, respectively and 47% also showed a low-grade endometrioid component. Most patients presented at an early stage (67%) and upon follow-up, 18% died of disease, 65% showed no evidence of disease, while 18% are alive with disease. Patients with MMR-D UCS are younger than the reported median age (70 y) for traditional UCS and most do not show p53 abnormalities. Low-grade endometrioid and undifferentiated carcinoma were seen in approximately half of all cases. Although UCSs have a high tendency for early extrauterine spread, most patients in our cohort presented at an early stage and at follow-up were no evidence of disease. MMR-D UCSs display distinct clinical, morphologic, and molecular features compared with traditional UCSs. © 2020 Lippincott Williams and Wilkins. All rights reserved.
Keywords: microsatellite instability; dna mismatch repair deficiency; hypermutated phenotype; uterine carcinosarcomas
Journal Title: American Journal of Surgical Pathology
Volume: 44
Issue: 11
ISSN: 0147-5185
Publisher: Lippincott Williams & Wilkins  
Date Published: 2020-11-01
Start Page: 1573
End Page: 1579
Language: English
DOI: 10.1097/pas.0000000000001561
PUBMED: 32804882
PROVIDER: scopus
PMCID: PMC8259346
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85092944711&doi=10.1097%2fPAS.0000000000001561&partnerID=40&md5=042f3577379dcce2eb1888e32cbd8f64
Notes: Article -- Export Date: 2 November 2020 -- Source: Scopus
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MSK Authors
  1. Nadeem Abu-Rustum
    888 Abu-Rustum
  2. Robert Soslow
    797 Soslow
  3. Deborah F DeLair
    106 DeLair
  4. Britta Weigelt
    633 Weigelt
  5. Sheila Elaika Segura
    12 Segura
  6. Silvana Pedra Nobre
    24 Pedra Nobre
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