Kutsal Yörükoğlu

Primary pigmented nodular adrenocortical disease (PPNAD) is a rare genetic disease mainly associated with Carney complex (CNC), which is caused by germline mutations of the regulatory subunit type 1A (RIα) of the cAMP-dependent protein kinase (PRKAR1A) gene. We report three cases suffering from CNC with unique features in diagnosis and follow-up. All cases had obesity and a cushingoid appearance and exhibited laboratory characteristics of hypercortisolism. However biochemical and radiological examinations initially suggested Cushing's disease in one case . All of the cases were treated surgically; two of them underwent bilateral adrenalectomy at once, one of them had unilateral adrenalectomy at first but required contralateral adrenalectomy after nine months. Contrary to what is usually known regarding PPNAD, the adrenal glands of two cases (case 2 and 3) had a macronodular morphology. Genetic analyses revealed pathogenic variants in PRKAR1A (case 1: c.440+5 G>A, not reported in the literature; cases 2 and 3: c.349G>T, p.V117F). One case developed Hodgkin lymphoma five year after adrenalectomy, this association was not previously reported with CNC. The findings of these families provide important information for a better understanding of the genetic pathogenesis, diagnosis, and clinical management of CNC. Hodgkin lymphoma may be a component of CNC.

Context: Neutrophil‐to‐lymphocyte ratio (NLR) and platelet‐to‐lymphocyte ratio (PLR) have recently emerged in assessing pheochromocytomas and paragangliomas (PPGLs). However, their combined use with PASS scale has not yet been explored.Objective: Our goal was to investigate the prognostic values of NLR and PLR and incorporate the PASS score into our analysis.Methods: Data from 74 histologically confirmed pheochromocytomas/paragangliomas across two centres were assessed. Poor prognosis was characterised by the presence of metastasis or disease‐specific mortality. Clinical characteristics such as age, gender, primary tumour size and location, and urinary metanephrine and normetanephrine levels, alongside NLR, PLR, and the PASS score as prognostic markers, were analysed. The prognostic value of the PASS score combined with NLR or PLR was evaluated using Receiver Operating Characteristic Curve (ROC), univariate, and multivariate regression analyses.Results: Sixty‐four patients with better prognosis and 10 patients with poor prognosis were included in the analysis, with mean PASS scores of 4 and 9, respectively. Poor prognosis was significantly higher in patients with NLR Á 3.43 (Area Under Curve(AUC) = 0.761; 70% sensitivity, 82.8% specificity, 38.9% PPV and 94.7% NPV) and with PLR > 193.12 (AUC = 0.738; 70% sensitivity, 76.2% specificity, 30% PPV and 94% NPV). The PASS and preoperative NLR or PLR combination predicted poor prognosis significantly in the multivariate models (OR: 125; 95% CI: 6.25–∞; p = 0.001 for PASS ≥ 6 and NLR > 3.43 and OR: 28.57; 95% CI: 3–250; p = 0.003 for PASS ≥ 6 and PLR > 193.12).Conclusion: As the roles of NLR and PLR in prediction of prognosis is gaining recognition, combining these with PASS score may improve preoperative stratification of prognosis and management of patients.

The aim of the study was to demonstrate the most common genetic alterations and evaluate possible targets involving phosphatidylinositol-3-OH kinase (PIK3)/AKT/mammalian target of rapamycin (mTOR) signaling and DNA damage repair (DDR) pathways for personalized treatment in patients with non-muscle invasive bladder cancer (NMIBC). Alterations of these pathways were observed in 89.5% and 100% of patients, respectively. Among them, BARD1 was more frequently altered in low/intermediate-risk cases, but PARP4 was more frequently affected in intermediate/high-risk patients. The possible target feasibility of BARD1 and PARP4 alterations should be evaluated for personalized treatment using PARP-inhibitors in NMIBC. It is important to detect high tumor mutation burden (TMB) in patients in terms of immunotherapy.

Aim: To evaluate the ex vivo efficacy of chemotherapy, immunotherapy and targeted agents with the oncogram method in patients with bladder cancer and determine the most appropriate personalized tre... Plain language summary Bladder cancer primary cell cultures were shown to be effective for drug sensitivity and also able to be used ex vivo in the process of determining personalized treatment. Th... Tweetable abstract Evaluation of drug responses detected by oncogram can provide important information for pretreatment drug selection when determining individualized treatment. These results show ...

Prostate cancer is one of the most common cancer for men worldwide with advanced forms showing supernumerary or clustered centrosomes. Hematological and neurological expressed 1 (HN1) also known as Jupiter Microtubule Associated Homolog 1 (JPT1) belongs to a small poorly understood family of genes that are evolutionarily conserved across vertebrate species. The co-expression network of HN1 from the TCGA PRAD dataset indicates the putative role of HN1 in centrosome-related processes in the context of prostate cancer. HN1 expression is low in normal RWPE-1 cells as compared to cancerous androgen-responsive LNCaP and androgen insensitive PC-3 cells. HN1 overexpression resulted in differential response for cell proliferation and cell cycle changes in RWPE-1, LNCaP, and PC-3 cells. Since HN1 overexpression increased the proliferation rate in PC-3 cells, these cells were used for functional characterization of HN1 in advanced prostate carcinogenesis. Furthermore, alterations in HN expression led to an increase in abnormal to normal nuclei ratio and increased chromosomal aberrations in PC-3 cells. We observed the co-localization of HN1 with γ-tubulin foci in prostate cancer cells, further validated by immunoprecipitation. HN1 was observed as physically associated with γ-tubulin and its depletion led to increased γ-tubulin foci and disruption in microtubule spindle assembly. Higher HN1 expression was correlated with prostate cancer as compared to normal tissues. The restoration of HN1 expression after silencing suggested that it has a role in centrosome clustering, implicating a potential role of HN1 in cell division as well as in prostate carcinogenesis warranting further studies.

Background: Epstein criteria based on sextant biopsy are assumed to be valid for 12-core biopsies. However, very scarce information is present in the current literature to support this view. Objectives: To investigate the validity of Epstein criteria for clinically insignificant prostate cancer (PCa) in a cohort of the currently utilized 12-core prostate biopsy (TRUS-Bx) scheme in patients with low-risk and intermediate-risk PCa. Method: Pathological findings were separately evaluated in the areas matching the sextant biopsy (6-core paramedian) scheme and in all 12-core schemes. Patients were divided into 2 groups according to the final pathology report of RP as true clinically significant PCa (sPCa) and insignificant PCa (insPCa) groups. Predictive factors (including Epstein criteria) and cutoff values for the presence of insPCa were separately evaluated for 6- and 12-core TRUS-Bx schemes. Then, different predictive models based on Epstein criteria with or without additional biopsy findings were created. Results: A total of 442 patients were evaluated. PSA density, biopsy GS, percentage of tumor and number of positive cores, PNI, and HG-PIN were independent predictive factors for insPCa in both TRUS-Bx schemes. For the 12-core scheme, the best cutoff values of tumor percentage and number of positive cores were found to be ≤50% (OR: 3.662) and 1.5 cores (OR: 2.194), respectively. The best predictive model was found to be that which added 3 additional factors (PNI and HG-PIN absence and number of positive cores) to Epstein criteria (OR: 6.041). Conclusions: Using a cutoff value of “1” for the number of positive biopsy cores and absence of biopsy PNI and HG-PIN findings can be more useful for improving the prediction model of the Epstein criteria in the 12-core biopsy scheme.