Investigation of Ki67 and Phospho-Histone H3 Expressions in Urothelial Carcinoma of the Bladder by Immunohistochemical Method.

BACKGROUND: In our study, it is aimed to investigate the relationship between Ki67 and phospho-histone H3 (pHH3) expressions in bladder urothelial carcinomas, with clinicopathological parameters and survival, which have prognostic value. METHODS: The study included 44 cases of high-grade urothelial carcinoma (HGUC), 37 cases of low-grade urothelial carcinoma (LGUC), and 11 nontumoral bladder cases. Ki67 and pHH3 were applied to the paraffin blocks of the tissues of 81 urothelial carcinoma and 11 nontumoral bladder cases by immunohistochemical method. Percentages of Ki67 and pHH3 expressions were evaluated by digital imaging analysis method. Expression percentages were compared with various clinicopathological parameters, and the relationship between them was evaluated. RESULTS: Ki67 was expressed in 28% of urothelial carcinoma cases and 1% of nontumoral cases. pHH3 was expressed in 10.32% of urothelial carcinoma cases and 0.16% of nontumoral cases. In our study, we found significantly higher Ki67 and pHH3 expressions in urothelial carcinoma compared to nontumoral cases. There was a statistically significant relationship (p < 0.05) and a positive correlation between Ki67 expression and lymphovascular invasion, pT stage, and histological grade. A statistically significant relationship (p < 0.05) and a positive correlation were found between pHH3 expression and lymphovascular invasion, pT stage, recurrence, and histological grade. In addition, a statistically significant relationship was found between Ki67 and pHH3 expressions. In our study, survival was found to be low in high-grade urothelial carcinoma cases with lymphovascular invasion, advanced age (65 years and older), and high Ki67 and pHH3 expression rates. CONCLUSIONS: According to our findings, high Ki67 and pHH3 expressions were found to be associated with poor prognostic parameters such as advanced pathologic stage, high histologic grade, and low survival. Our findings suggest that Ki67 and pHH3 may play a role in the differentiation, progression, and aggressive behavior of urothelial carcinoma. However, further studies are needed to confirm our findings and determine the role of these markers in urothelial carcinoma.

The effect of Vortioxetine on the NLRP3 pathway and microglial activity in the prefrontal cortex in an experimental model of depression.

BACKGROUND: Increasing evidence suggests that early life stress (ELS) and neuroinflammation are associated with the pathophysiology of depression. The purpose of this study was to determine the effects of Vortioxetine (VOR), a novel antidepressant, on ELS-induced behavioral changes and neuroinflammation. METHOD: Wistar Albino 4-week-old male rats were divided into four groups: control; chronic unpredictable stress (CUMS), VOR, CUMS + VOR. Neurobehavioral assessment was performed on the first, 21st, and 42nd days. RT-PCR was used to detect the expression of P2X7, NLRP3, IL1ß, IL18 in the prefrontal cortex. To assess the microglial activities of the prefrontal cortex, immunohistochemically stained CD68, and leukocyte common antigen (LCA) preparations were scanned with Manual WSI software, Basler camera, and scored. RESULT AND DISCUSSION: Exposure to CUMS was associated with depression and anxiety-like behaviors, and administration of VOR led to improvement in these behaviors. NLRP3, IL-1ß, and IL-18 were shown to be upregulated in the prefrontal cortex of CUMS rats, while their high expression was inhibited by VOR treatment. CD68 and LCA expressions were significantly higher in the CUMS group compared to the other groups. CONCLUSION: According to these results, it may be considered that NLRP3 inflammasome-associated neuroinflammatory response and microglial activation may play a role in the etiopathogenesis of ELS.

Prognostic value of claudin 18.2 expression in gastric adenocarcinoma.

BACKGROUND: Claudin 18.2 (CLDN18.2) is a cell surface protein expressed by gastric cancer cells. The monoclonal antibody zolbetuximab binds CLDN18.2-positive cancer cells and causes cancer cell death. A few studies researched the prognostic effect of CLDN18.2 expression in metastatic gastric adenocarcinoma. AIM: To identify the prognostic value of CLDN18.2 expression in patients with metastatic gastric adenocarcinoma. METHODS: This study was conducted with 65 patients over the age of 18 who were diagnosed with metastatic gastric adenocarcinoma. We investigated the effect of CLDN18.2 expression on clinicopathological characteristics (age, sex, histological grade, Lauren classification, family history, metastatic site, HER2 expression) and prognosis for patients with metastatic gastric adenocarcinoma. RESULTS: CLDN18.2 expression was positive in 73.8% (48) of the patients. During the median 17.7-mo follow-up period, 89.2% (58) of the patients died. Median progression-free survival and overall survival (OS) were 6 mo (95% confidence interval: 1.6-10.4) and 12 mo (95% confidence interval: 7.5-16.5). There was no statistically significant correlation between CLDN18.2 expression and clinicopathological characteristics of the patients. In univariate and multivariate Cox regression analysis, there was no correlation between clinicopathological characteristics of patients and progression-free survival or OS. CONCLUSION: CLDN18.2 expression was quite high in patients with gastric adenocarcinoma, identifying the proportion of the patients in whom zolbetuximab would be efficacious. There is no statistically significant correlation with clinicopathological characteristics and OS. CLDN18.2 is not a prognostic marker in patients with gastric adenocarcinoma, although it is predictive.

The expression of stanniocalcin-1, estrogen receptor and progesterone receptor in endometrioid endometrial cancer.

Objective: To evaluate the expression of stanniocalcin-1 (STC-1) and to investigate the correlation of STC-1 with expression of estrogen receptor (ER), progesterone receptor (PR) and clinical parameters, histopathological findings and prognostic factors in endometrioid endometrial cancer (EEC). Materials and Methods: In this retrospective study, STC-1 (cytoplasmic), ER (nuclear), and PR (nuclear) stainings were applied to tissue microarray sections of 89 EEC, 27 endometrial intraepithelial neoplasia (EIN), and 21 normal endometrium (NE). Prognostic factors such as age, tumor size, depth of myometrial invasion, lymphovascular invasion, perineural invasion, and lymph node metastasis were compared with the expression of these markers. Results: ER showed significantly higher positivity in grade 1 EEC. PR expression was also higher in grade 1 EEC, but these findings were not statistically significant. Strong expression of STC-1 was observed in EIN and EECs compared with NE. STC-1 showed low staining in the NE, and high staining was also noted in the EIN foci adjacent to the NE. STC-1 expression was positively correlated with grade 1 EECs. Conclusion: STC-1 expression was positively correlated with low histologic grade in EECs. STC-1 can be used for distinguishing low-grade endometrioid tumors and high -grade endometrioid tumors in curretage specimens. Since STC-1 is related to well differentiated tumors, it can also be regarded as a good prognostic factor in EECs.

The role of claudin 18.2 and HER-2 in pancreatic cancer outcomes.

To examine the prognostic value of claudin 18.2 (CLDN18.2) and human epidermal growth factor receptor-2 (HER-2) expression in patients with resected pancreatic ductal adenocarcinoma (PDAC). This study enrolled patients who underwent surgery and were diagnosed with PDAC at Suleyman Demirel University Hospital, Turkey between 2015 and 2019. Sixty-eight patients with resected PDAC treated at a medical oncology clinic were assessed. All patients were over the age of 18 years, underwent follow-up and treatment in our unit, and had pathology slides that we could access. Clinicopathological data were obtained from medical files, including the patients' age, sex, pathological parameters, and clinical stage according to the Eighth International Union against Cancer/American Joint Committee on Cancer. Patient survival and the period from the date of diagnosis to death were assessed in the follow-up data. There was no statistically significant difference between CLDN18.2 and HER-2 expression scores for samples and patient clinicopathological characteristics. No HER-2 expression scores of ≥2 were found in the samples. Only 25% (n = 17) of the samples had HER-2 expression scores of +1. CLDN18.2 expression was detected in 54.4% (n = 37) of the patient samples. CLDN18.2 expression scores were +1 in 30.8% (n = 21) of the patient samples, +2 in 16.2% (n = 11), and +3 in 7.4% (n = 5). When CLDN18.2 and HER-2 expression were compared, a statistically significant difference and moderate positive correlation were observed. No significant relationship between HER-2 expression and survival was observed in the survival analysis of PDAC patients; however, high CLDN18.2 expression was related to longer overall survival. Our study is the third to research CLDN18.2 expression in PDAC. HER-2 expression is low and CLDN18.2 expression is high in patients with PDAC. HER-2 expression is not related to overall survival but CLDN18.2 is related and may be used as a prognostic marker in patients with PDAC.

Diagnostic and prognostic value of Stanniocalcin 1 expression in papillary thyroid cancer.

PURPOSE: To evaluate the potential role of immunohistochemical changes in stanniocalcin 1 (STC1) and stanniocalcin 2 (STC2) expressions in papillary thyroid cancer (PTC) tissues in the disease's diagnosis and to investigate their relationship with classical clinicopathological prognostic factors. METHODS: The study included 100 patients with PTC. Normal thyroid tissue adjacent to the tumor was taken as the control group. Clinicopathological prognostic features at the time of diagnosis of patients were recorded. STC1 and STC2 expressions of tumor tissue and adjacent normal tissue were determined immunohistochemically. RESULTS: The sensitivity of STC1 in the diagnosis of PTC was 93%, the specificity was 94%, positive predictive value (PPV) 93.9%, and negative predictive value (NPV) 93.1%. It was determined that the STC1 staining score in tumor tissue was positively correlated with the disease TNM stage score (r = 0.259, p = 0.009) and the increase in STC1 staining score were independent risk factors that increased the risk of lymph node metastasis (R2 = 0.398, p < 0.001). While 21% of the tumor tissues were stained with STC2, none of the normal thyroid tissues adjacent to the tumor tissue showed any staining with STC2. No correlation was found between STC2 immunohistochemical staining of tumor tissue and clinicopathological risk factors for the disease. CONCLUSION: Increased STC1 expression in thyroid lesions may be helpful in diagnosing PTC. In addition, since increased STC1 expression in PTC tissues is associated with the risk of lymph node metastasis, it may be an efficient marker for predicting the prognosis of the disease.