Overexpression of Connexin 40 in the Vascular Endothelial Cells of Placenta with Acute Chorioamnionitis.

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.

Placental Cyclophilin A Expression in Pregnancies Complicated with Hypertension.

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.

Long term outcome of immunoglobulin A (IgA) nephropathy: A single center experience.

INTRODUCTION: IgA nephropathy (IgAN) has a heterogeneous presentation and the progression to end stage renal disease (ESRD) is often influenced by demographics, ethnicity, as well as choice of treatment regimen. In this study, we investigated the long term survival of IgAN patients in our center and the factors affecting it. METHODS: This study included all biopsy-proven IgAN patients with ≥ 1year follow-up. Patients with diabetes mellitus at diagnosis and secondary IgAN were excluded. Medical records were reviewed for demographics, clinical presentation, blood pressure, 24-hour urine protein, serum creatinine, renal biopsy and treatment received. The primary outcome was defined as combined event of 50% estimated glomerular filtration rate (eGFR) reduction or ESRD. RESULTS: We included 130 (74 females; 56 males) patients of mean age 38.0 ± 14.0 years and median eGFR of 75.2 (interquartile range (IQR) 49.3-101.4) ml/min/1.73m2. Eighty-four (64.6%) were hypertensive at presentation, 35 (26.9%) had nephrotic syndrome and 57 (43.8%) had nephrotic range proteinuria (NRP). Median follow-up duration was 7.5 (IQR 4.0-13.0) years. It was noted that 18 (13.8%) developed ESRD and 34 (26.2%) reached the primary outcome. Annual eGFR decline was -2.1 (IQR -5.3 to -0.1) ml/min/1.73m2/year, with median survival of 20 years. Survival rates from the combined event (50% decrease in eGFR or ESRD) at 10, 20 and 30 years were 80%, 53% and 25%, while survival from ESRD were 87%, 73% and 65%, respectively. In the univariate analysis, time-average proteinuria (hazard ratio (HR) = 2.41, 95% CI 1.77-3.30), eGFR <45ml/min/1.73m2 at biopsy (HR = 2.35, 95% CI 1.03-5.32), hypertension (HR = 2.81, 95% CI 1.16-6.80), mean arterial pressure (HR = 1.02, 95% CI 1.01-1.04), tubular atrophy/interstitial fibrosis score (HR = 3.77, 95% CI 1.84-7.73), and cellular/fibrocellular crescent score (HR = 2.44, 95% CI 1.19-5.00) were found to be significant. Whereas only time-average proteinuria (TA-proteinuria) remained as a significant predictor in the multivariate analysis (HR = 2.23, 95% CI 1.57-3.16). CONCLUSION: In our cohort, TA-proteinuria was the most important predictor in the progression of IgAN, irrespective of degree of proteinuria at presentation.

A study of HER2 expression in endometrial carcinoma: a single centre experience.

INTRODUCTION: endometrial carcinoma (EC) is the seventh most common cancer in females in Malaysia, of which the majority is composed of lower grade type I EC. Although less prevalent, type II EC which is of higher grade has poorer outcome and prognosis. Human epidermal growth factor receptor 2 (HER2) is one of the possible prognostic molecular markers which can be a target for immunotherapy. This study aimed to assess the expression of HER2 in common type of EC in the local population and to determine its correlation with the clinicopathological features. METHODS: a total of 53 cases of endometrioid type of EC were selected within a six-year period comprising of 22 cases of grade 1, 25 cases of grade 2 and six cases of grade 3 carcinoma. The selected whole tumour tissue sections were immune-stained with HER2 antibody. The scoring was semi-quantitatively analyzed based on 2013 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAPs) guidelines for the scoring of HER2 in breast cancer. RESULTS: all cases regardless of grades of endometrioid carcinoma showed negative expression of HER2 (score 0). CONCLUSION: there was no significant HER2 expression in endometrioid carcinoma. However, a follow-up study with a larger number of samples from different type of endometrial carcinoma is needed. Testing of several tumour tissue blocks to assess possible tumour heterogeneity, as well as correlation with HER2 gene amplification status by in-situ-hybridisation, are also recommended.

Programmed Death Ligand 1: A Poor Prognostic Marker in Endometrial Carcinoma.

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.