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    BRAF mutation, TERT promoter mutation, and HER2 amplification in sporadic or neurofibromatosis-related neurofibromas and malignant peripheral nerve sheath tumors: do these molecules have a signature in malignant transformation?
    (Wiley, 2020) Coskun, Sinem; Gamsizkan, Mehmet; Yilmaz, Ismail; Yalcinkaya, Ulviye; Sungur, Mehmet Ali; Buyucek, Seyma; Onal, Binnur
    Peripheral nerve sheath tumors may occur sporadically or related to neurofibromatosis (NF). Unless the mechanisms of tumorigenesis in NF related malignant peripheral nerve sheath tumors (MPNST) are better understood, it remained unclear in sporadic cases. We aimed to investigate the genetic route for malignancy in both individuals with NF-1 and sporadic ones to open a way for targeted therapies in the future. We investigated the role of HER2 with Dual ISH DNA Probe Cocktail test, BRAF mutation (exon 15) and TERT promoter mutation frequency with Sanger sequencing method in respectively 25 sporadic neurofibromas, 25 NF-1 related neurofibromas and 25 MPNST cases from two institutes. Categorical data were analyzed and summarized as frequency and percentage. Statistical analysis was done with SPSS v.22 statistical package, and the statistical significance level was considered as 0.05. We identified TERT promoter mutation only in one sporadic MPNST (4%) and no BRAF mutation in any case. HER2 amplification is found in 10/25 (40%) MPNST cases. No mutations or gene amplification detected in neurofibromas (p < 0.001). MPNSTs are sarcomas with poor prognosis and limited treatment options. TERT promoter mutations and HER2 amplification may play a putative role in therapeutic purposes.
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    Expressions of p53, KAI1, PTEN and their use as prognostic markers in urothelial carcinoma of the bladder
    (Kuwait Medical Assoc, 2020) Celik, Ozgur Ilhan; Celik, Serkan Yasar; Han, Unsal; Onal, Binnur
    Objectives: To determine the expression levels of p53, KAI1, PTEN and their relations with the clinicopathologic parameters in patients with urothelial carcinoma of the bladder Design: Retrospective study Setting: Department of Pathology, Ankara Diskapi Yildirim Beyazit Education and Research Hospital, Ankara, Turkey Subjects: Seventy-eight patients with a diagnosis of urothelial carcinoma of the bladder at the Pathology Department of Ankara Diskapi Yildirim Beyazit Education and Research Hospital and who were followed up for two years Intervention: Archived pathology materials of all patients were reviewed and clinical data were collected from medical database records retrospectively. Main outcome measures: We considered the following parameters: age, gender, survivals and disease-free survivals of the patients, tumor-stage, lymphovascular-angiovascular invasions, expressions of KAI1, PTEN and p53 in tumorous tissues. Results: In non-metastatic-patients, 55.2% were p53 negative; however, 45.8% of the metastatic-patients had diffuse-strong p53-expressions. Hence, p53 positivity indicates that the tumor will metastase. In transurethral resection (TUR) materials, patients with positive KAI1-expression had better survival (p=0.0285). The tumor seemed to be more aggressive and invasive in patients with decreased KAI1-expressions because there was no KAI1 expression in 50% of the metastatic-patients, although it wasn't statistically significant (p=0.550). For PTEN expression, no statistically-significant relation was found with the tumor-stage (p=0.34) and survival/ disease-free-survival (TUR:p=0.9599/0.7576, radical cystectomy :p=0.8219/0.5790). Conclusions: The presence of metastasis dramatically decreases the overall survival in patients with urothelial carcinoma. Identification of these patients as early as possible would effect their therapies, follow-up intervals and surveys. p53 and KAI1 seem to be especially better indicators of the prognosis than PTEN.
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    KRAS, BRAF, PIK3CA mutation frequency of radical prostatectomy samples and review of the literature
    (Taylor & Francis Ltd, 2021) Bahcivan, Atike; Gamsizkan, Mehmet; Coskun, Sinem Kantarcioglu; Cangur, Sengul; Yuksel, Alpaslan; Ceyhan, Aysegul; Onal, Binnur
    Objective The molecular basis of prostate cancer is highly heterogeneous. Our study aimed to perform the mutation analysis of KRAS, BRAF, PIK3CA, and immunohistochemical (IHC) evaluation of EGFR, HER2, p16, and PTEN to demonstrate new areas for targeted therapies. Methods A total of 24 prostatectomy samples diagnosed with adenocarcinoma were analyzed by microarray hybridization. Also, these samples were IHC stained for EGFR, HER2, P16, and PTEN. The cases were divided into two groups based on low and high Gleason scores. All findings were compared with the clinicopathological parameters of the patients. Results While KRAS mutation was in 3/24 (12.5%) of our cases, BRAF and PIK3CA mutations were not detected. There was no significant difference between the groups in terms of KRAS mutation frequency. HER2 was immunohistochemically negative in all samples. There was no correlation between EGFR, P16 immunopositivity, and clinicopathological features. Conclusion KRAS mutation frequency is similar to those in Asian populations. BRAF and PIK3CA mutation frequencies have been reported in the literature in the range of 0-15% and 0-10.4%, respectively, consistent with our study findings. HER2 immunoexpression is a controversial issue in the literature. EGFR and p16 expressions may not correlate with the stage.
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    Prevalence of High-Risk Human Papillomavirus Types and Their Association with Cervical Squamous Cell Carcinoma, and High- and Low-Grade Squamous Intraepithelial Lesions in Turkish Women
    (Iranian Scientific Society Medical Entomology, 2023) Erkinueresin, Taskin; Kartal, Esra; Ustunyurt, Emin; Demirci, Hakan; Kilitci, Asuman; Onal, Binnur
    Background: This study aimed to investigate human papillomavirus (HPV) type prevalence in our region and the relationship between uterine cervical HPV types and squamous cell carcinoma (SCC)/intraepithelial lesions.Methods: HPV test results were obtained from patient file archives of the Gynecology and Obstetrics Clinic. Pathology report results were obtained from the digital records of the Pathology Laboratory and the patient file archives of the Gynecology and Obstetrics Clinic in 2018.Results: The most frequently detected was HPV16 (29.2%), followed by HPV51 (13.1%), HPV56 (11%), HPV31 (9.2%), HPV52 (8.4%), and HPV68 (8.2%). HPV16 was positive in 50% of patients diagnosed with SCC, 54.9% of patients with HSIL, 27% of patients with LSIL, and 25% of cases diagnosed as benign (P<0.001). HPV18 was positive in 25% of patients diagnosed with SCC, 11% of patients with HSIL, 4.7% of patients with LSIL, and 5.2% of cases diagnosed as benign (P=0.019).Conclusion: The most frequent hrHPV genotype was HPV16, followed by HPV51, HPV 56, and HPV 31. There is an increase in the frequency of HPV51 and HPV56. HPV51, not included in HPV vaccines and is the second most frequent, should be included in these vaccines. In addition, although the frequency of HPV18 has decreased, HSIL and SCC generation is still high together with HPV16.
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    Recommendations for immunocytochemistry in lung cancer typing: An update on a resource-efficient approach with large-scale comparative Bayesian analysis
    (Wiley, 2021) Elmas, Hatice; Diel, Roland; Onal, Binnur; Sauter, Guido; Stellmacher, Florian; Welker, Lutz
    Objectives The majority of lung cancer cases are of advanced stage and diagnosis is usually made using minimally invasive small biopsies and cytological specimens. The WHO 2015 classification recommends limiting immunocytochemistry (ICC) to lung cancer typing and molecular testing drives for personalised therapies. An algorithm using Bayes' theorem could be useful for defining antibody profiles. This study aims to assess the impact of different antibody profiles for cytological samples on the accuracy of lung cancer typing with a large-scale Bayesian analysis. Methods A retrospective examination of 3419 consecutive smears and/or cytospins diagnosed over 2011-2016 found 1960 primary lung cancer tumours: 972 adenocarcinomas (ADC), 256 squamous carcinomas (SQC), 268 neuroendocrine tumours (NET), and 464 non-small cell cancer-not otherwise specified (NSCC-NOS). The a priori and a posteriori probabilities, before and after ICC using antibodies singly or in combination, were calculated for different lung cancer types. Results TTF-1 or CK7 alone improved the a posteriori probabilities of correct cytological typing for ADC to 86.5% and 95.8%, respectively. For SQC, using p40 ( increment Np63) or CK5/6 together with CK5/14 led to comparable results (78.3% and 90.3%). With synaptophysin or CD56 alone, improvements in a posteriori probabilities to 87.5 and 90.3% for the correct recognition of NET could be achieved. Conclusions Based on morphological and clinical data, the use of two antibodies appears sufficient for reliable detection of the different lung cancer types. This applies to diagnoses that were finalised following ICC both on a clinical or cytological basis and on a histological basis.
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    Shear Wave Ultrasound Elastography and Diffusion-Weighted Magnetic Resonance Imaging Findings of Pleural Based Masses with Histopathologic Correlation
    (Duzce Univ, Fac Medicine, 2021) Unlu, Elif Nisa; Altinsoy, Hasan Baki; Balaby, Ege Gulec; Sungur, Mehmet Ali; Boran, Mertay; Onal, Binnur
    Objective: The study aims to evaluate the usefulness of non-invasive diagnostic methods, shear wave elastography (SWE), and diffusion-weighted magnetic resonance imaging (DWI) to differentiate benign and malignant lesions in the thoracic pleural based masses by comparing them with histopathological findings. Methods: Sixty-three patients having a pleural-based peripheral mass on computed tomography (CT), admitted to the interventional radiology department for transthoracic biopsy, were included in the study. All patients underwent DWI, and ADC values of the groups were measured. Transthoracic biopsy was performed with the guidance of US from the area where the highest shear wave velocity (SWV) value was calculated. ADC and SWV values of histopathologically proven benign and malignant lesions were statistically compared. Results: Fifty-six patients were male, and seven were female. The mean age was 64.68 +/- 10.13 years (41-85 years). Fourty-four patients were malignant, and 19 were benign. The maximum SWV was found to be 4.13 +/- 0.59 m/s in malignant cases and 3.55 +/- 0.71 m/s in benign cases, and the difference was significant (p = 0.001). Mean ADC value was measured as 1.04 +/- 0.30 x 10-3 mm2/s in malignant cases and 1.32 +/- 0.33 x 10-3 mm2/s in benign cases on DWI and the difference was significant (p = 0.002). In malignant cases, the minimum ADC was 0.73 +/- 0.29 x 10-3 mm2/s, and 0.99 +/- 0.44 x 10-3 mm2/s in benign cases, the difference was significant (p = 0.024). ROC analysis revealed a cut-off value of >= 4.08 m/s for SWVmax, <= 1.01x10-3 mm2/s for mean ADC, and <0.8x10-3 mm2/s for minimum ADC showed a significant performance in distinguishing malignant and benign lesions. Conclusions: Transthoracic US elastography and DWI are useful in differentiating malignant and benign lesions in appropriate cases. Both SWE and DWI are useful in routine use because they are non-invasive and do not contain radiation. In particular, SWE is suitable for biopsy guidance and may prevent the possibility of insufficient material.