Clinicopathological significance of protein disulphide isomerase A3 and phosphorylated signal transducer and activator of transcription 3 in cervical carcinoma.

Introduction: Death in cervical cancer patients is usually due to invasion and metastasis due to the aggressive nature of the tumour. Therefore, it is critical to identify potent therapeutic targets and prognostic markers to detect high-risk patients. Material and methods: We assessed the immunohistochemical expression of protein disulphide isomerase A3 (PDIA3) and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in 50 cases of cervical carcinoma, and we investigated their association with clinicopathological characteristics. Results: High PDIA3 was detected in 50% of cases, and statistical analysis revealed a positive correlation between high PDAI3 expression and tumour grade (p < 0.001) and large tumour size (p = 0.010), depth of stromal invasion (p = 0.017), lymph-vascular invasion (p = 0.005), parametrial invasion (p < 0.001), nodal metastasis (p < 0.001), and higher International Federation of Gynaecology and Obstetrics stages (p < 0.001). Positive nuclear expression of p-STAT3 was detected in 44% of cases and showed significant association with histological grade (p = 0.036), tumour stage (p = 0.021), nodal metastasis (p = 0.020), and parametrial invasion (p = 0.045); statistical analysis of the patient's survival data revealed that shorter overall survival and disease-free survival, S, were associated with high PDIA3 expression and positive p-STAT3 immunoexpression. Conclusions: The high expression of PDIA3 and p-STAT3 was related to highly aggressive cervical carcinoma with poor prognosis, and high risk of recurrence after the standardised protocol of treatment. Hence, both PDIA3 and p-STAT3 could be considered as novel biomarkers for tumour progression and promising targets in the management of cervical carcinoma patients.

Clinicopathologic Impact of NANOG, ZEB1, and EpCAM Biomarkers on Prognosis of Serous Ovarian Carcinoma.

OBJECTIVES: Serous ovarian carcinoma (SOC) is a biologically heterogeneous with different genomic and molecular profiles, beside clinical response to the chemotherapy with subsequent in obstacles in starting unified, acceptable treatments and so we assess immunoexpression of Nanog, ZEB1, and EpCAM in SOC. METHODS: In this study, the immunoexpression of Nanog, ZEB1, and EpCAM was studied in 60 cases of SOC. Overall survival (OS), disease-free survival (DFS) data and response to chemotherapy were  analyzed. RESULTS: NANOG was immunostained in 65% of the cases with a significant association with tumor grade, lymph node metastasis, and FIGO stage (p < 0.001 for each). ZEB1 showed moderate- high expression in 58.3% of the cases with significant up-regulation of ZEB1 expression with SOC grade, nodal metastasis, and SOC FIGO stage (p<0.001). EpCAM revealed high expression in 60% of the cases with significant association with higher grade, nodal metastasis, and advanced stage (p < 0.001 for each). Up-regulation of Nanog was significantly associated with response to chemotherapy, relapse, shorter OS and DFS (p < 0.001 for each). ZEB1 overexpression exhibited a significant association with response to chemotherapy (p= 0.012), relapse, shorter OS and DFS (p<0.001 for each). Moreover, the high EpCAM had a significant association with response to chemotherapy (p= 0.043), relapse (p < 0.001) shorter OS (p=0.006) and DFS (p< 0.001). CONCLUSIONS: Up-regulation of Nanog and ZEB-1 and EpCAM perhaps promote an aggressive SOC with a high risk of relapse and unfavorable response to standard chemotherapy regimen.

An in vivo confocal masked study on corneal epithelium and subbasal nerves in patients with dry eye.

PURPOSE: The objective of the present study was to determine whether dry eye (DE) associated with primary Sjögren's syndrome (PSDE) and DE not associated with Sjögren's syndrome (NSDE) are related to an alteration of corneal innervation. METHODS: Eleven healthy volunteers younger than 60 years (normal [N] < 60 group), 10 healthy volunteers 60 years of age or older (N > or = 60 group), 11 patients with PSDE, and 10 patients with NSDE were studied. Epithelial and stromal density and subbasal and stromal nerves were investigated by confocal microscopy. RESULTS: The density of the superficial epithelial cells was 741 +/- 306 cells/mm2 in the PSDE group; 1022 +/- 331 cells/mm2 in the NSDE group; 1523 +/- 294 cells/mm2 in the N > or = 60 group, and 1529 +/- 341 cells/mm2 in the N < 60 group (P < 0.0001, ANOVA). The number of subbasal nerves was 2.8 +/- 1.2 in the PSDE group, 3.3 +/- 0.7 in the NSDE group, 3.1 +/- 0.9 in the N > or = 60 group, and 4.6 +/- 0.8 in the N < 60 group (P < 0.0001, ANOVA). The number of beadlike formations observed in the different groups was 387 +/- 62/mm in the PSDE group, 323 +/- 64/mm in the NSDE group, 182 +/- 63/mm in the N > or = 60 group, and 198 +/- 66/mm in the N < 60 group (P < 0.0001, ANOVA). A correlation was found between the number of subbasal nerves and age (P < 0.01) and between the number of subbasal nerves and Schirmer's test (P < 0.001, Spearman rho). CONCLUSIONS: Patients with DE show alteration in the corneal innervations. The demonstration of such alterations introduces new strategies for treatment of this frequent disease.