Chronic endometritis (CE) is a continuous inflammation of uterine endometrium, and it is usually symptomless. As CE has been thought not to affect the reproductive status and general health of affected women, its significance has not been explored. However, recent studies have shown that CE is related with repeated implantation failures after in vitro fertilization-embryo transfer, unexplained infertility, and recurrent miscarriages. As decidua differentiates to support the implantation process and maintains the pregnancy, we hypothesized that CE may influence the process of decidualization. Seventeen patients were employed in the experiment involving culture of endometrial stromal cells (ESCs). After obtaining endometrial samples, ESCs were harvested and cultured for 13 days. The concentrations in culture media and the protein expressions in ESCs of prolactin (PRL) and insulin-like growth factor binding protein-1 (IGFBP-1), two well known decidualization markers used in a large number of in vitro models, were analyzed by ELISA and Western blotting, respectively, and the cell numbers were also counted. The mRNA levels of PRL and IGFBP-1 were tested by quantitative real time polymerase chain reaction (RT-PCR). Since sex hormone induce proliferation and differentiation to decidua via binding to the sex hormone receptors (ERα, ERβ, PRA, and PRB), their expression was assessed in another 17 patients’ paraffin-embedded endometrial tissue specimens by immunohistochemistry and semi-quantified by H-score. Increased cell numbers and reduced secretion of PRL and IGFBP-1 were detected by ELISA in the ESCs of CE patients after culture for 13 days compared with non-CE patients. The decreased protein expression of IGFBP-1 in ESCs of CE patients was detected by Western blotting. The decreased expression of PRL mRNA and IGFBP-1 mRNA were detected by RT-PCR. Increased expressions of ERα, ERβ, PRA, and PRB were observed in the stromal cells of CE patients in comparison to non-CE patients, whereas increased expressions of ERα and ERβ were detected in the glandular cells of CE. Our data suggests that CE modifies decidualization of human ESC through untuning the function of sex steroid hormone receptor.

Background: Cancer-associated fibroblasts (CAFs) are some of the most abundant components of the tumour microenvironment. A recent study suggested that in some cancers, CAFs express programmed death ligand 1 (PD-L1), which can act as a prognostic marker. The aim of this study was to investigate the clinicopathological significance of CAF PD-L1 expression in patients with triple-negative breast cancer (TNBC) and to identify the most suitable primary antibody for immunostaining for CAF PD-L1. Methods: Immunohistochemical staining (primary antibodies of 73–10, SP142, and E1L3N) and tissue microarrays were used to analyse the expression profiles of PD-L1 in CAF in 61 patients with TNBC who underwent surgery. Overall survival (OS) was compared based on CAF PD-L1 expression, and the risk factors for OS were analysed. The relationship between clinicopathological parameters and survival was also examined. Results: Thirty-four (55.7%) patients were positive for CAF PD-L1 (73–10) expression. Compared with CAF PD-L1 negativity, there was a significant correlation between CAF PD-L1 positivity and better OS (p = 0.029). CAF PD-L1 expression, evaluated using SP-142 or E1L3N, did not correlate with OS. CAF PD-L1-positivity (73–10) correlated significantly with better prognosis in multivariate analyses (hazard ratio: 0.198; 95% confidence interval: 0.044–0.891; p = 0.035). Conclusions: CAF PD-L1 expression is a novel marker for a better prognosis of patients with TNBC, and the 73–10 assay may be suitable for immunostaining CAF PD-L1.

Background: Stromal reaction is an important prognostic factor in several cancers, and the presence of myxoid change was assessed as a poor prognostic factor in colorectal cancer. However, the prognostic significance of myxoid change in triple-negative breast cancer (TNBC) remains unknown. This study aimed to determine the prognostic significance of myxoid change and fibrotic focus (FF), which is a fibrotic area within the tumor and considered a poor prognostic indicator in patients with TNBC. Methods: We enrolled 62 patients with TNBC and reviewed the surgically resected specimens to evaluate myxoid change and FF in the tumor using previously outlined criteria. We evaluated tumor-infiltrating lymphocytes (TILs) using hematoxylin and eosin slides. Overall survival (OS) and relapse-free survival (RFS) were compared based on the presence of myxoid change and/or FF, and the risk factors for RFS were analyzed. Results: Myxoid change and FF were observed in 25.8% and 33.9% of specimens, respectively. Based on stromal lymphocyte infiltration, 19 patients (30.6%) had high TILs, while the remaining 43 patients (69.4%) had low/intermediate TILs. Presence of myxoid change was significantly correlated with poor OS and RFS (p = 0.040 and 0.031, respectively). FF was also significantly correlated with poor OS and RFS (p = 0.012 and 0.028, respectively). The combination of myxoid change and FF was an independent and poor prognostic factor according to the multivariate analysis (HR 11.61; 95% CI 1.027–131.2; p = 0.048). Presence of myxoid change and FF were significantly associated with low/intermediate TILs in the stroma (p = 0.013). Conclusions: Histopathological assessment of myxoid change and FF in TNBC may be a useful, practical, and easily assessable method for predicting prognosis in patients with TNBC, which should be confirmed in larger prospective studies. Diagnostic criteria for the establishment of myxoid change and FF in TNBC must be established, and their underlying molecular events must be clarified.

Background: The purpose of the present study was to evaluate the relationship between chronic endometritis and the epithelial-mesenchymal transition in the endometrium of infertile patients in the implantation phase. Methods: Endometrial biopsy specimens from 66 infertility patients were analyzed. The presence of chronic endometritis was investigated by immunostaining for CD138. Immunohistochemical staining for E-cadherin, N-cadherin, Slug, and Snail was performed, and the expression profiles were statistically analyzed according to the presence of chronic endometritis. When the loss of E-cadherin expression and/or the positive expression of N-cadherin was detected, the specimen was considered epithelial-mesenchymal transition-positive. Epithelial-mesenchymal transition-positive cases were also statistically analyzed according to the presence of chronic endometritis. The characteristics of the patients in the epithelial-mesenchymal transition-positive and epithelial-mesenchymal transition-negative groups were compared. The association between variables, including age, body mass index, gravidity, parity, and each causative factor of infertility and epithelial-mesenchymal transition positivity was analyzed. Results: The rates of the loss of E-cadherin expression, the gain of N-cadherin and epithelial-mesenchymal transition positivity were significantly higher in chronic endometritis patients. The expression of Slug, cytoplasmic Snail, and nuclear Snail was also detected at significantly higher rates in chronic endometritis patients. Chronic endometritis were related to the epithelial-mesenchymal transition. Conclusion: The epithelial-mesenchymal transition was frequently detected in the endometrium in infertile patients with chronic endometritis. Since the epithelial-mesenchymal transition is associated with chronic endometritis, the epithelial-mesenchymal transition appears to be involved in the alteration of mechanisms of implantation.

Background: Traditionally, the treatment options for unresectable locally advanced (UR-LA) and metastatic (UR-M) pancreatic ductal adenocarcinoma (PDAC) are palliative chemotherapy or chemoradiotherapy. The benefits of surgery for such patients remains unknown. The present study investigated clinical outcomes of patients undergoing conversion surgery (CS) after chemo(radiation)therapy for initially UR-PDAC. Methods: We recruited patients with UR-PDAC who underwent chemo(radiation)therapy for initially UR-PDAC between April 2006 and September 2017. We analyzed resectability of CS, predictive parameters for overall survival, and early recurrence (within six months). Results: A total of 468 patients (108 with UR-LA and 360 with UR-M PDAC) were enrolled in this study, of whom, 17 (15.7%) with UR-LA and 15 (4.2%) with UR-M underwent CS. The median survival time (MST) and five-year survival of patients who underwent CS was 37.2 months and 34%, respectively; significantly better than non-resected patients (nine months and 1%, respectively, p < 0.0001). MST did not differ according to UR-LA or UR-M (50.5 vs. 29.0 months, respectively, p = 0.53). Early recurrence after CS occurred in eight patients (18.8%). Lymph node metastasis, positive washing cytology, large tumor size (>35 mm), and lack of postoperative adjuvant chemotherapy were statistically significant predictive factors for early recurrence. Moreover, the site of pancreatic lesion and administration of postoperative adjuvant chemotherapy were statistically significant prognostic factors for overall survival in the patients undergoing CS. Conclusion: Conversion surgery offers benefits in terms of increase survival for initially UR-PDAC for patients who responded favorably to chemo(radiation)therapy when combined with postoperative adjuvant chemotherapy.