We analyzed mismatch repair (MMR) protein expression by immunohistochemistry in EIN/AH concurrent with MMR-deficient endometrial carcinomas, and in endometrial biopsy/curettage specimens with EIN/AH from an unselected group of patients.
ProMisE was applied to a retrospective cohort of women with ECs <50 yo at diagnosis, and associations between the four ProMisE molecular subtypes (MMR deficient (MMRd), POLE mutated (POLE), p53 wild type (p53wt), and p53 abnormal (p53abn)) and clinicopathological parameters, including outcomes, were assessed.
It has poor prognosis compared with Grade 3 endometrioid adenocarcinoma and is often associated with the loss of mismatch repair (MMR) proteins, which is seen in microsatellite instability (MSI)-type endometrial cancer.
The PROMISE diagnostic algorithm, which uses p53, mismatch repair (MMR) protein immunohistochemistry, and DNA polymerase ε (POLE) exonuclease domain mutation testing, is a reliable surrogate of the molecular group in endometrial carcinoma.
Lynch Syndrome (LS) patients harbor germline mutations in one of several mismatch repair (MMR) genes and are predisposed to the development of colon and endometrial cancers and multiple other cancers types as well.
Extensive hypermethylation of the MLH1 promoter was observed in 69.6% ECs with MLH1 deficiency and 3.5% with MMR proficiency, but in none of the ECs with loss of other MMR genes (P < .0001).
The aim of this study was to investigate the prognostic value of the Hedgehog (Gli, Patched-1, Shh, Smo) and Notch (Jag1, Notch2, Notch3) pathway members, in comparison to a panel of proteins (ER, PgR, HER2/neu, Ki67, p53, p16, PTEN and MMR) previously suggested to be involved in the pathogenesis of endometrial cancer, in association with clinical outcome and standard clinicopathological characteristics.
Advanced endometrial cancer can rarely (~7%) show somatic loss of MMR protein expression in recurrent or metastatic sites compared to matched paired primary tumor.
Loss of MMR proteins has been shown to correlate with tumoral PD-L1 expression in colorectal and endometrial carcinomas, but the association between expression of MMR proteins and PD-L1 has not previously been studied in breast carcinoma, where MMR deficiency is less common.
Reflexive testing for MMR protein loss by immunohistochemistry (IHC) is currently only recommended for colorectal and endometrial cancers, although upper tract urothelial carcinoma (UTUC) is the third-most common malignancy in patients with LS.
Additionally, 19.2% of patients displayed deficiency in at least 1 MMR protein, with a significantly higher proportion of MMR protein deficiency in the PFH group than in the NFH group (adjusted OR = 4.81, 95% CI: 2.14-8.83).Clinicopathologic features differ for young patients with EC with and without a family history of cancer.
In addition, we analyzed a cohort of 138 endometrial cancers (EC) by immunohistochemistry to determine MMR protein expression and validation of our new MSI assay.
Immunohistochemistry (IHC) for the presence or absence of mismatch repair (MMR) proteins (to identify MMR deficiency [MMR-D]), sequencing for polymerase-ɛ (POLE) exonuclease domain mutations (POLE EDMs), and IHC for tumor protein 53 (p53) (wild type vs null/missense mutations; p53 wt and p53 abn, respectively) were performed on 319 new EC samples.
Monoallelic germline mutations in one of the DNA mismatch repair (MMR) genes cause Lynch syndrome, with a high lifetime risks of colorectal and endometrial cancer at adult age.
Although consensus has yet to be reached on universal mismatch-repair (MMR) protein immunohistochemical (IHC) screening for Lynch syndrome (LS) in endometrial cancer (EC), an increasing number of institutions have adopted universal screening protocols similar to those used for colorectal carcinoma.
Although many studies have evaluated the impact of mismatch repair protein loss of expression (MMR LOE) or microcystic, elongated, and fragmented (MELF) pattern of myometrial invasion as individual factors in endometrial cancer, we analyzed the combined impact of both.
Risk was also evaluated for family history of up to three cancers from known familial syndromes (Lynch, Cowden, hereditary breast and ovarian cancer) overall, by histological subtype and, for a subset of 678 patients, by EC tumor mismatch repair (MMR) gene expression.
In our study, 151 endometrial carcinomas were molecularly categorized using sequencing for the exonuclease domain mutations (EDM) of POLE, and immunohistochemistry for p53 and mismatch repair (MMR) proteins.
Lynch syndrome (LS) is an autosomal-dominant inherited disorder mainly caused by a germline mutation in the DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2) and is associated with increased risk for various cancers, particularly colorectal cancer and endometrial cancer (EC).