Nurwardah Alfian

Background: This study investigated PD-L1 and EZH2 immunoexpressions in endometrial carcinomas (ECs) and correlated their associations with clinicopathological parameters and five-year survival outcomes. Methods: A cross-sectional, retrospective study was conducted on all ECs diagnosed between January 2014 and December 2018. Immunohistochemical staining for PD-L1 (clone 22C3) and EZH2 was performed on tumour samples, and their expression levels were assessed. Results: Among the 104 EC cases included, 19.2% (n = 20) overexpressed PD-L1, while 8.7% (n = 9) overexpressed EZH2. Most (n = 19/20, 95.0%) PD-L1-expressing tumour cells showed EZH2 immunonegativity. Likewise, most (n = 8/9, 88.9%) EZH2-expressing ECs were PD-L1-negative. Increased PD-L1 and EZH2 expressions in ECs were seen more frequently in women more than 60 years of age (p = 0.013 and p = 0.039). EZH2 overexpression was associated with higher tumour grade (p = 0.009) and more aggressive histological subtypes (p = 0.013), while PD-L1 expression was not significantly associated with tumour grade, tumour stage, histological subtypes, and lymph node status (p > 0.05). Kaplan–Meier survival analysis revealed that PD-L1-positive ECs had a significantly better five-year overall survival (OS) rate compared to PD-L1-negative ECs (p = 0.034). Conversely, EZH2 overexpression did not correlate with survival outcomes (p > 0.05). Notably, the combination of PD-L1 and EZH2 expression patterns on ECs (PD-L1-/EZH2+) portends the worst OS compared to other combined PD-L1/EZH2 expression patterns (p = 0.05). Conclusions: PD-L1 immunoexpression was associated with better survival outcomes in ECs, while overexpression of EZH2 was associated with higher tumour grade and aggressive histological subtypes, suggesting their potential utility as prognostic biomarkers in ECs.

Background: Connexins (Cx) 43 and 40 play a role in leukocytes recruitment in acute inflammation. They are expressed in the endothelial cells. They are also found in the placenta and involved in the placenta development. Acute chorioamnionitis is associated with an increased risk of adverse perinatal outcomes. The aim of this study was to determine the expressions of Cx43 and Cx40 in the placenta of mothers with acute chorioamnionitis, and to correlate their association with the severity of chorioamnionitis and adverse perinatal outcomes. Methods: This study comprised a total of 81 cases, consisting of 39 placenta samples of mothers with acute chorioamnionitis and 42 non-acute chorioamnionitis controls. Cx43 and Cx40 immunohistochemistry were performed on all cases and their expressions were evaluated on cytotrophoblasts, syncytiotrophoblasts, chorionic villi endothelial cells, stem villi endothelial cells, maternal endothelial cells and decidua of the placenta. Results: Primigravida has a significantly higher risk of developing acute chorioamnionitis (p < 0.001). Neonates of mothers with a higher stage of fetal inflammatory response was significantly associated with lung complications (p = 0.041) compared to neonates of mothers with a lower stage. The expression of Cx40 was significantly higher in fetal and maternal vascular endothelial cells in acute chorioamnionitis (p < 0.001 and p = 0.037, respectively) compared to controls. Notably, Cx43 was not expressed in most of the types of cells in the placenta, except for decidua. Both Cx43 and Cx40 expressions did not have correlation with the severity of acute chorioamnionitis and adverse perinatal outcomes. Conclusion: Cx40 was overexpressed in the fetal and maternal vascular endothelial cells in the placenta of mothers with acute chorioamnionitis, and it may have a role in the development of inflammation in placenta.

Introduction: Cyclophilin A was reported to be increased in the serum of mothers with preeclampsia, and is implicated in its pathogenesis. This study aimed to determine the expression of cyclophilin A in the placenta of mothers with and without hypertension, and to correlate its expression with maternal complications and adverse perinatal outcomes. Materials and Methods: This study consisted of a total of 70 cases (35 cases of mothers with hypertension, and 35 normotensive mothers as a control). Cyclophilin A immunohistochemistry was performed on a paraffin-embedded tissue section of placenta submitted at full thickness in order to evaluate the expression in fetal endothelial cells, cytotrophoblasts, syncytiotrophoblasts, maternal endothelial cells and decidual cells. The cyclophilin A expression was scored as weak, moderate or strong intensity. Results: The hypertensive group was more likely to have preterm deliveries (p < 0.0001), caesarean sections (p < 0.0001), and infants admitted to the intensive care unit (p < 0.001). Fifty-one percent of the fetal endothelial cells and cytotrophoblasts expressed cyclophilin A in the hypertensive group, compared to only 28.6% in the normotensive group. However, the difference was not statistically significant (p = 0.086). Conclusion: We found no significant difference in placental cyclophilin A expression between hypertensive and normotensive mothers. There was also no difference in expression in mothers with and without maternal complications and adverse perinatal outcomes.

Endometrial carcinoma is the only gynaecologic malignancy with a raising incidence and mortality, posing a major health concern worldwide. The upregulation of programmed death ligand 1 (PD-L1) on tumour cells causes T-cell suppression, which impedes antitumour immunity, promotes immune cell evasion and enhances tumour survival. The aim of this study was to evaluate PD-L1 expression in endometrial carcinoma and to correlate it with survival rate. A total of 59 cases of endometrial carcinoma were evaluated. Thirty-two cases of non-neoplastic endometrial tissue were included as control. PD-L1 immunohistochemistry was performed on all cases. PD-L1 expression was evaluated on tumour cells and immune cells. PD-L1 was positive in 62.7% (37/59) and 28.8% (17/59) of immune cells and tumour cells, respectively. PD-L1 expression in immune cells was significantly higher in endometrial carcinoma than in non-neoplastic endometrium (p < 0.001). Among the patients with endometrial carcinoma, PD-L1 expression in tumour cells was significantly higher in patients who died (10/15, 66.7%) compared to those who survived (7/44, 15.9%) (p < 0.001). It is noteworthy to point out that the expression of PD-L1 in tumour cells was significantly associated with a poor survival. This suggests that immunomodulation using PD-L1 inhibitors may be useful in advanced endometrial carcinoma.