Endometrial Cytology in Diagnosis of Endometrial Cancer: A Systematic Review and Meta-Analysis of Diagnostic Accuracy.

BACKGROUND: Because the incidence of endometrial cancer has been increasing every year, it is important to identify an effective screening method for it. The endometrial cytology test (ECT) is considered to be the more acceptable technique compared to invasive endometrial sampling. METHODS: The study followed the Priority Reporting Project for Systematic Evaluation and Meta-Analysis (PRISMA-DTA) protocol. This systematic rating searched EMBASE and Web of Science databases for studies on ECT for endometrial cancer from the databases' dates of inception to 30 September 2022. All literature screening and data extraction were performed by two researchers, while the methodological quality of the included studies was assessed against defined inclusion criteria. And a third researcher resolves the disagreements. RESULTS: Twenty-six studies were eventually included in this final analysis. Meta-analysis results showed that the diagnostic accuracy characteristics of ECT for endometrial cancer were as follows: combined sensitivity = 0.84 [95% confidence interval (CI) (0.83-0.86)], combined specificity = 0.98 [95% CI (0.98-0.98)], combined positive likelihood ratio = 34.65 [95% CI (20.90-57.45)], combined negative likelihood ratio = 0.21 [95% CI (0.15-0.30)], and area under the summary receiver operating characteristic curve = 0.9673. CONCLUSIONS: ECT had the ability to detect endometrial cancer with strong specificity, although some studies have demonstrated significant differences in sensitivity.

High expression of crystallin αB represents an independent molecular marker for unfavourable ovarian cancer patient outcome and impairs TRAIL- and cisplatin-induced apoptosis in human ovarian cancer cells.

Dysregulated apoptotic pathways are regarded as major reasons for chemoresistance development as a particular challenge in ovarian cancer therapy. In search of molecular factors affecting human ovarian cancer cell apoptosis and, consequently, patient survival, we examined tumors of 103 platinum-/taxane-treated ovarian cancer patients by mRNA-array hybridization, qPCR, and immunohistochemistry. We identified high expression of crystallin αB (CRYAB), a proposed negative regulator of tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-mediated apoptosis. By Kaplan Meier analysis, this factor turned out to be significantly associated with poor patient outcome [overall survival (OS) p = 0.001, recurrence-free survival (RFS) p = 0.003]. Elevated hazard ratios (HR) were estimated with regard to OS (HR = 2.11, 95% CI 1.10-4.06) and RFS (HR = 1.92, 95% CI 1.07-3.47) in multivariable analyses. These associations were confirmed in independent, publicly available mRNA data comprising 431 patients for OS (p < 0.001) and 413 for RFS (p < 0.001). Our findings were validated by studying apoptotic events in cultured human ovarian cancer cells which were stably transfected to express elevated CRYAB levels. These data emphasized the crucial role of CRYAB in human ovarian cancer biology since TRAIL- as well as cisplatin-induced apoptosis was significantly impaired as a function of enhanced CRYAB expression. Taken together, we identified CRYAB as an independent biomarker for unfavourable outcome of human ovarian cancer patients. Since TRAIL is currently tested as anti-cancer drug and large proportions of the present patient cohort displayed low CRYAB levels in their tumors, CRYAB may enable the selection of patient subgroups benefiting most from TRAIL-containing therapy.

Neutrophil gelatinase-associated lipocalin (NGAL) predicts response to neoadjuvant chemotherapy and clinical outcome in primary human breast cancer.

In our previous work we showed that NGAL, a protein involved in the regulation of proliferation and differentiation, is overexpressed in human breast cancer (BC) and predicts poor prognosis. In neoadjuvant chemotherapy (NACT) pathological complete response (pCR) is a predictor for outcome. The aim of this study was to evaluate NGAL as a predictor of response to NACT and to validate NGAL as a prognostic factor for clinical outcome in patients with primary BC. Immunohistochemistry was performed on tissue microarrays from 652 core biopsies from BC patients, who underwent NACT in the GeparTrio trial. NGAL expression and intensity was evaluated separately. NGAL was detected in 42.2% of the breast carcinomas in the cytoplasm. NGAL expression correlated with negative hormone receptor (HR) status, but not with other baseline parameters. NGAL expression did not correlate with pCR in the full population, however, NGAL expression and staining intensity were significantly associated with higher pCR rates in patients with positive HR status. In addition, strong NGAL expression correlated with higher pCR rates in node negative patients, patients with histological grade 1 or 2 tumors and a tumor size <40 mm. In univariate survival analysis, positive NGAL expression and strong staining intensity correlated with decreased disease-free survival (DFS) in the entire cohort and different subgroups, including HR positive patients. Similar correlations were found for intense staining and decreased overall survival (OS). In multivariate analysis, NGAL expression remained an independent prognostic factor for DFS. The results show that in low-risk subgroups, NGAL was found to be a predictive marker for pCR after NACT. Furthermore, NGAL could be validated as an independent prognostic factor for decreased DFS in primary human BC.

Electrofusion generates diverse DC-tumour cell hybrids for cancer immunotherapy.

BACKGROUND: Hybrid cells generated from dendritic cells (DC) and tumour cells provide tumour-associated antigens (TAA) in a polyvalent mode. The present study was designed to investigate the hybrid cell generation by dendritic cells and different tumour cell lines to establish an electrofusion protocol with an optimal fusion setting. MATERIALS AND METHODS: Hybrid cells from mature DC and tumour cells were generated by electrofusion. Fusion efficiency was determined by flow cytometry, as well as by light and fluorescence microscopy analyses. RESULTS: The gradual electrofusion process constituted different human dendritic cell tumour cell hybrids of high diversity depending on electrical and non-electrical parameters. Factors influencing fusion frequency were determined by specific cell staining with mAbs, FACS analysis and trypan blue dye exclusion. CONCLUSION: Increased fusion efficiency was associated with reduced viability. The protocol presented in this work might be helpful for future fusion studies as a prerequisite for comparable in vitro and human vaccination trials.