Article Text
Abstract
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.