Mismatch repair markers in preoperative and operative endometrial cancer samples; expression concordance and prognostic value

Background The endometrial cancer mismatch repair (MMR) deficient subgroup is defined by loss of MSH6, MSH2, PMS2 or MLH1. We compare MMR status in paired preoperative and operative samples and investigate the prognostic impact of differential MMR protein expression levels. Methods Tumour lesions fr...

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Bibliographic Details
Published in:British journal of cancer 2023-02, Vol.128 (4), p.647-655
Main Authors: Berg, Hege F., Engerud, Hilde, Myrvold, Madeleine, Lien, Hilde E., Hjelmeland, Marta Espevold, Halle, Mari K., Woie, Kathrine, Hoivik, Erling A., Haldorsen, Ingfrid S., Vintermyr, Olav, Trovik, Jone, Krakstad, Camilla
Format: Article
Language:English
Subjects:
631/337/1427/2121
631/67/1517/1931
692/4028/67/1517/1931
692/53/2422
692/699/67/1517
Biomedical and Life Sciences
Biomedicine
Cancer
Cancer Research
Curettage
DNA Mismatch Repair
Drug Resistance
Endometrial cancer
Endometrial Neoplasms - pathology
Endometrium
Epidemiology
Female
Gene expression
Humans
Hysterectomy
Lymph nodes
Medical prognosis
Metastases
Mismatch repair
Mismatch Repair Endonuclease PMS2 - genetics
MLH1 protein
MMR protein
Molecular Medicine
MSH2 protein
MSH6 protein
MutL Protein Homolog 1 - genetics
MutS Homolog 2 Protein - genetics
Oncology
Prognosis
Protein expression
Proteins
Tumors
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Summary:Background The endometrial cancer mismatch repair (MMR) deficient subgroup is defined by loss of MSH6, MSH2, PMS2 or MLH1. We compare MMR status in paired preoperative and operative samples and investigate the prognostic impact of differential MMR protein expression levels. Methods Tumour lesions from 1058 endometrial cancer patients were immunohistochemically stained for MSH6, MSH2, PMS2 and MLH1. MMR protein expression was evaluated as loss or intact to determine MMR status, or by staining index to evaluate the prognostic potential of differential expression. Gene expression data from a local ( n  = 235) and the TCGA ( n  = 524) endometrial cancer cohorts was used for validation. Results We identified a substantial agreement in MMR status between paired curettage and hysterectomy samples. Individual high expression of all four MMR markers associated with non-endometrioid subtype, and high MSH6 or MSH2 strongly associated with several aggressive disease characteristics including high tumour grade and FIGO stage, and for MSH6, with lymph node metastasis. In multivariate Cox analysis, MSH6 remained an independent prognostic marker, also within the endometrioid low-grade subgroup ( P  
ISSN:0007-0920
1532-1827
DOI:10.1038/s41416-022-02063-3