Increased expression of YAP1 in prostate cancer correlates with extraprostatic extension.

Objective:Yes associated protein 1 (YAP1) is a member of the Hippo pathway, acting as a transcriptional coactivator. To elucidate the role of YAP1 and phosphorylated (p)YAP1 in prostate cancer (PCa) tumorigenesis, we investigated their expression in clinical samples of PCa and cell lines. Methods:Fifty-four tumor, adjacent nontumor, and prostate intraepithelial neoplasia (PIN) tissues from patients with PCa after radical prostatectomy were selected from a retrospective cohort and studied using immunohistochemistry (IHC). Protein and mRNA expression levels of YAP1 were evaluated by Western blot analysis and quantitative real-time reverse transcription PCR, respectively, in cancer cell lines. Publicly available gene expression datasets were downloaded to analyze YAP1 mRNA and protein levels in PCa tissue samples. Results:IHC analysis of PCa tissues revealed that YAP1 staining intensities were moderate to weak in the nucleus and cytoplasm of tumor cells, whereas adjacent normal epithelia showed strong staining. We observed that benign prostates were characterized by higher expression levels of both nuclear (P=0.004) and cytosolic (P=0.005) YAP1. pYAP1 staining was weak in the cytoplasm and absent in the nucleus of all the tissues investigated. YAP1 expression was an indicator of extraprostatic extension (EPE). The level of YAP1 was negatively correlated with the level of the androgen receptor (AR) in The Cancer Genome Atlas dataset and Western blot analysis of cell lines. Conclusions:Our study suggested that YAP1 expression is heterogeneous in PCa tissue samples; therefore, YAP1 might play different roles in different aspects of PCa progression. This might involve AR-YAP1 interplay in PCa

Prognostic significance of survivin, β-catenin and p53 expression in urothelial carcinoma

Survivin, β-catenin, and p53 are well-known cell-cycle and apoptosis regulators of tumorigenesis. Urothelial carcinomas (UCs) are the most common of the human cancers. Compared to superficial tumors (Ta, CIS, or T1), invasive UCs are important with regard to recurrence, progression, and mortality. Therefore, we examined whether survivin, β-catenin, and p53 could be used as the biomarkers for the early prediction of the invasiveness of UCs and the overall survival of the patients. We investigated the prognostic expressions of those biomarkers in UC (n=147) and in non-muscle invasive UC (NMI-UC) (n=113), using tissue microarray and immunohistochemistry. Spearman's correlation analysis and multivariate Cox regression analyses were used for statistical interpretation. High expressions of β-catenin, survivin, and p53 were associated with a high T stage, recurrence, progression, mortality, low recurrence-free survival, low progression-free survival and low overall survival (p < 0.01). Similar findings were achieved for recurrence and progression in the NMI-UC group, except for mortality. Moreover, a positive correlation was shown between p53 and β-catenin and between p53 and survivin (r=0.221, p < 0.01; r=0.236, p < 0.01, respectively). Survivin, p53, and β-catenin overexpression, as prognostic markers, might suggest that the UCs are biologically aggressive with the poor prognosis. Thus, dysregulation of those these cell-cycle and apoptosis regulators in bladder carcinoma could be used as a molecular marker to determine the best treatment strategy and could contribute to the development of targeted therapies

The relation of presenting symptoms with staging, grading, and postoperative 3-year mortality in patients with stage I-III non-metastatic colon cancer

Background/Aims: To evaluate the association of presenting symptoms with staging, grading, and postoperative 3-year mortality in patients with colon cancer. Materials and Methods: A total of 132 patients-with a mean (standard deviation; SD) age of 63.0 (10.0) years and of whom 56.0% were males-with non-metastatic stage I-III colon cancer were included. Symptoms prior to diagnosis were evaluated with respect to tumor localization, tumor node metastasis (TNM) stage, histological grade, and postoperative 3-year mortality. Results: Constipation and abdominal pain were the two most common symptoms appearing first (29.5% and 16.7%, respectively) and remained most predominant (25.0% and 20.0%, respectively) up to diagnosis. The frequency of admission symptoms significantly differed with respect to tumor location, TNM stage and histological grade. The postoperative 3-year survival rate was 61.4%. Multivariate logistic regression revealed that melena and rectal bleeding increased the likelihood of 3-year mortality by 13.6-fold (p=0.001) and 4.08-fold (p=0.011), respectively. Conclusion: Our findings revealed differences in presenting symptom profiles with respect to the time of manifestation and predominance as well as to the TNM stage, histological grade, and tumor location. Given that melena and rectal bleeding increased the 3-year mortality risk by 13.6-fold and 4.08-fold, respectively, our findings indicate the association of admission symptoms with outcome among patients with colon cancer

The ghrelin and orexin activity in testicular tissues of patients with idiopathic non-obstructive azoospermia

The aim of the present study is to evaluate the presence of ghrelin and orexin in the testicular tissue of patients who have undergone microscopic testicular sperm extraction (micro-TESE) due to idiopathic non-obstructive azoospermia. Seventy azoospermic cases were included in this study; serum hormone levels were measured and genetic investigations were performed. The patients were divided into two groups: micro-TESE (+) and micro-TESE (−). The number of Leydig cells and stained cells in the seminiferous tubules were counted under a light microscope, and we analyzed ghrelin and orexin activity. The relationship between serum hormone levels and ghrelin and orexin distributions in testicular tissue was evaluated according to micro-TESE results. While sperm was found in 33 cases (47.1%), micro-TESE was negative in 37 cases (52.9%). Peptide hormone activity in testicular tissue was higher in micro-TESE (+) cases. However, interstitial orexin (p = 0.038) and ghrelin (p = 0.002) activity showed statistically meaningful differences. Many different peptides, genes, and other unknown mechanisms play important roles in testicular function. In particular, the peptides orexin and ghrelin may play regulatory roles in testicular function in humans. Keywords: Ghrelin, Micro-TESE, Non-obstructive azoospermia, Orexi

Increased expression of YAP1 in prostate cancer correlates with extraprostatic extension.

ObjectiveYes associated protein 1 (YAP1) is a member of the Hippo pathway, acting as a transcriptional coactivator. To elucidate the role of YAP1 and phosphorylated (p)YAP1 in prostate cancer (PCa) tumorigenesis, we investigated their expression in clinical samples of PCa and cell lines.MethodsFifty-four tumor, adjacent nontumor, and prostate intraepithelial neoplasia (PIN) tissues from patients with PCa after radical prostatectomy were selected from a retrospective cohort and studied using immunohistochemistry (IHC). Protein and mRNA expression levels of YAP1 were evaluated by Western blot analysis and quantitative real-time reverse transcription PCR, respectively, in cancer cell lines. Publicly available gene expression datasets were downloaded to analyze YAP1 mRNA and protein levels in PCa tissue samples.ResultsIHC analysis of PCa tissues revealed that YAP1 staining intensities were moderate to weak in the nucleus and cytoplasm of tumor cells, whereas adjacent normal epithelia showed strong staining. We observed that benign prostates were characterized by higher expression levels of both nuclear (P=0.004) and cytosolic (P=0.005) YAP1. pYAP1 staining was weak in the cytoplasm and absent in the nucleus of all the tissues investigated. YAP1 expression was an indicator of extraprostatic extension (EPE). The level of YAP1 was negatively correlated with the level of the androgen receptor (AR) in The Cancer Genome Atlas dataset and Western blot analysis of cell lines.ConclusionsOur study suggested that YAP1 expression is heterogeneous in PCa tissue samples; therefore, YAP1 might play different roles in different aspects of PCa progression. This might involve AR-YAP1 interplay in PCa