Introduction/Background Mismatch repair system(MMR) deficiency is more common in endometrioid-type endometrial carcinomas(E-EC) than other endometrial tumors. It’s prognostic significance vary among different studies. Additional criteria are needed to predict outcome in MMR-deficient(MMRd) E-ECs.
Methodology 108 patients diagnosed with E-EC between 2020–2022 at our institution were included in the study. Of these, 51 were MMR-deficient immunohistochemically and remaining 57 were MMR-proficient(MMRp). Histopathological features like tumor size, FIGO grade&stage, lymphovascular invasion(LVI), MELF(microcystic,elongated&fragmanted)-type invasion, necrosis/comedonecrosis, psammoma bodies, depth-of-invasion, squamous/mucinous differentiation were noted for all cases. Previously performed immunohistochemical stains (MSH2,MSH6,PMS2,MLH1,ER,PR,p53) were reevaluated. Six tissue-microarray blocks were manually constructed with representative 2cores of 1mm2 for each case and immunohistochemistry was performed by using PD-L1,CD3,CD4,CD8,CD45,BRAF-VE1,CERB-B2 antibodies. Densities of CD3,CD4,CD8,CD45 positive immune-cells(IC) were calculated (positive-cells/mm2) both in the stromal&intratumoral compartments. PD-L1 scores were grouped as: negative,≤1%,2–20%,>20% of the tumor cells(TC) &ICs. CERB-B2 expression was evaluated as applied in breast cancer. BRAF-VE1 staining was evaluated in the tumor cells and grouped as negative/weak/moderate/strong.
Results Median follow-up time was 11 months(range:1–160). Mean tumor size was 37.22mm(range:7–160). Comparison of MMRd and MMRp group revealed that, MMRd-cases had the propensity for higher tumor size, FIGO grade&stage. Presence of comedonecrosis, psammoma bodies, diffuse LVI were more frequent, CD3&CD8 densities were higher in the MMRd-group. PD-L1 expression was higher in TC&ICs of MMRd-tumors. A statistically significant correlation between the presence of extensive necrosis and tumor recurrence/metastasis was detected within the MMRd-group(p=0.004), despite of no such relation within the MMRp-group. Recurrence/metastasis rates were significantly higher in BRAF positive cases among all E-ECs(p=0.021).
Conclusion CD3,CD8 positive lymphocytes constituted the majority of ICs in MMRd-cases and PD-L1 expression was also higher in MMRd-group. Extent of necrosis may be important criteria for predicting outcome in MMRd E-ECs. BRAF expression significantly correlated with recurrence/metastasis in all E-ECs, independently of MMR status, and maybe promising as a prognostic parameter for E-ECs.
Disclosures The authors have no conflict of interest to declare.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.