File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Clinical Behavior and Molecular Landscape of Stage I p53-Abnormal Low-Grade Endometrioid Endometrial Carcinomas

TitleClinical Behavior and Molecular Landscape of Stage I p53-Abnormal Low-Grade Endometrioid Endometrial Carcinomas
Authors
Issue Date1-Dec-2023
PublisherAmerican Association for Cancer Research
Citation
Clinical Cancer Research, 2023, v. 29, n. 23, p. 4949-4957 How to Cite?
Abstract

Purpose:

The clinical significance of the p53-abnormal (p53abn) molecular subtype in stage I low-grade endometrioid endometrial carcinoma (EEC) is debated. We aimed to review pathologic and molecular characteristics, and outcomes of stage I low-grade p53abn EEC in a large international cohort.

Experimental Design:

Previously diagnosed stage I p53abn EC (POLE–wild-type, mismatch repair–proficient) low-grade EEC from Canadian retrospective cohorts and PORTEC-1&2 trials were included. Pathology review was performed by six expert gynecologic pathologists blinded to p53 status. IHC profiling, next-generation sequencing, and shallow whole-genome sequencing was performed. Kaplan–Meier method was used for survival analysis.

Results:

We identified 55 stage I p53abn low-grade EEC among 3,387 cases (2.5%). On pathology review, 17 cases (31%) were not diagnosed as low-grade EEC by any pathologists, whereas 26 cases (47%) were diagnosed as low-grade EEC by at least three pathologists. The IHC and molecular profile of the latter cases were consistent with low-grade EEC morphology (ER/PR positivity, patchy p16 expression, PIK3CA and PTEN mutations) but they also showed features of p53abn EC (TP53 mutations, many copy-number alterations). These cases had a clinically relevant risk of disease recurrence (5-year recurrence-free survival 77%), with pelvic and/or distant recurrences observed in 12% of the patients.

Conclusions:

A subset of p53abn EC is morphologically low-grade EEC and exhibit genomic instability. Even for stage I disease, p53abn low-grade EEC are at substantial risk of disease recurrence. These findings highlight the clinical relevance of universal p53-testing, even in low-grade EEC, to identify women at increased risk of recurrence.


Persistent Identifierhttp://hdl.handle.net/10722/337403
ISSN
2023 Impact Factor: 10.0
2023 SCImago Journal Rankings: 4.623

 

DC FieldValueLanguage
dc.contributor.authorJamieson, Amy-
dc.contributor.authorVermij, Lisa-
dc.contributor.authorKramer, Claire JH-
dc.contributor.authorJobsen, Jan J-
dc.contributor.authorJürgenliemk-Schulz, Ina-
dc.contributor.authorLutgens, Ludy-
dc.contributor.authorMens, Jan Willem-
dc.contributor.authorHaverkort, Marie AD-
dc.contributor.authorSlot, Annerie-
dc.contributor.authorNout, Remi A-
dc.contributor.authorOosting, Jan-
dc.contributor.authorCarlson, Joseph-
dc.contributor.authorHowitt, Brooke E-
dc.contributor.authorIp, Philip PC-
dc.contributor.authorLax, Sigurd F-
dc.contributor.authorMcCluggage, W Glenn-
dc.contributor.authorSingh, Naveena-
dc.contributor.authorMcAlpine, Jessica N-
dc.contributor.authorCreutzberg, Carien L-
dc.contributor.authorHoreweg, Nanda-
dc.contributor.authorGilks, C Blake-
dc.contributor.authorBosse, Tjalling-
dc.date.accessioned2024-03-11T10:20:36Z-
dc.date.available2024-03-11T10:20:36Z-
dc.date.issued2023-12-01-
dc.identifier.citationClinical Cancer Research, 2023, v. 29, n. 23, p. 4949-4957-
dc.identifier.issn1078-0432-
dc.identifier.urihttp://hdl.handle.net/10722/337403-
dc.description.abstract<p>Purpose:</p><p>The clinical significance of the p53-abnormal (p53abn) molecular subtype in stage I low-grade endometrioid endometrial carcinoma (EEC) is debated. We aimed to review pathologic and molecular characteristics, and outcomes of stage I low-grade p53abn EEC in a large international cohort.</p><p>Experimental Design:</p><p>Previously diagnosed stage I p53abn EC (<em>POLE</em>–wild-type, mismatch repair–proficient) low-grade EEC from Canadian retrospective cohorts and PORTEC-1&2 trials were included. Pathology review was performed by six expert gynecologic pathologists blinded to p53 status. IHC profiling, next-generation sequencing, and shallow whole-genome sequencing was performed. Kaplan–Meier method was used for survival analysis.</p><p>Results:</p><p>We identified 55 stage I p53abn low-grade EEC among 3,387 cases (2.5%). On pathology review, 17 cases (31%) were not diagnosed as low-grade EEC by any pathologists, whereas 26 cases (47%) were diagnosed as low-grade EEC by at least three pathologists. The IHC and molecular profile of the latter cases were consistent with low-grade EEC morphology (ER/PR positivity, patchy p16 expression, <em>PIK3CA</em> and <em>PTEN</em> mutations) but they also showed features of p53abn EC (<em>TP53</em> mutations, many copy-number alterations). These cases had a clinically relevant risk of disease recurrence (5-year recurrence-free survival 77%), with pelvic and/or distant recurrences observed in 12% of the patients.</p><p>Conclusions:</p><p>A subset of p53abn EC is morphologically low-grade EEC and exhibit genomic instability. Even for stage I disease, p53abn low-grade EEC are at substantial risk of disease recurrence. These findings highlight the clinical relevance of universal p53-testing, even in low-grade EEC, to identify women at increased risk of recurrence.</p>-
dc.languageeng-
dc.publisherAmerican Association for Cancer Research-
dc.relation.ispartofClinical Cancer Research-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleClinical Behavior and Molecular Landscape of Stage I p53-Abnormal Low-Grade Endometrioid Endometrial Carcinomas-
dc.typeArticle-
dc.identifier.doi10.1158/1078-0432.CCR-23-1397-
dc.identifier.volume29-
dc.identifier.issue23-
dc.identifier.spage4949-
dc.identifier.epage4957-
dc.identifier.eissn1557-3265-
dc.identifier.issnl1078-0432-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats