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1. Lysyl Oxidase Like-4 (LOXL4) as a tumor marker and prognosticator in advanced stage laryngeal cancer

Author

Altuntaş, Muzaffer Ozan (ORCID 0000-0002-8747-7420 & YÖK ID 169795), Süslü, N.; Güler Tezel, Y.G.; Tatlı Doğan, H.; Yılmaz, T., School of Medicine, Altuntaş, Muzaffer Ozan (ORCID 0000-0002-8747-7420 & YÖK ID 169795), Süslü, N.; Güler Tezel, Y.G.; Tatlı Doğan, H.; Yılmaz, T., and School of Medicine

Abstract

Introduction: Lysyl oxidase-like 4 is an amine oxidase from the lysyl oxidase family that was previously shown to be overexpressed in head and neck cancer and upregulated in response to hypoxia. The possible role of lysyl oxidase-like 4 as a tumor marker in advanced stage larynx cancer was investigated. Objective: To investigate the expression of lysyl Oxidase-Like 4 protein in advanced stage laryngeal cancer and elucidate its possible role as a tumor marker, predictor of treatment response and prognosticator. Methods: Diagnostic specimens of 72 patients treated for stage III–IV laryngeal squamous cell carcinoma were evaluated for lysyl oxidase-like 4 expression by immunohistochemistry. Results: Lysyl oxidase-like 4 expression was correlated with advanced tumor stage (p = 0.041) and better differentiation (p = 0.025) but was independent of tumor diameter (p = 0.456). Response to induction chemotherapy or the need for salvage laryngectomy were not affected by lysyl oxidase-like 4 expression (p = 0.999, p = 0.070 respectively). Increased lysyl oxidase-like 4 expression was associated with better 2 year overall survival in both univariate (p = 0.036) and multivariate analyses (p = 0.014). Conclusion: Lysyl oxidase-like 4 expression emerges with advancing stages, is lost with worsening differentiation, and may have tumor suppressive properties in larynx cancer., This research was funded by a research grant from the Scientific Research Projects Commission of Hacettepe University.

Published
2022

3. What does the Data of 354,725 Patients from Turkey Tell Us About Cervical Smear Epithelial Cell Abnormalities? - the Epithelial Cell Abnormality Rate is Increasing - Quality Control Studies and Corrective Activity are Musts

Author

Eken Kg, Binnur Onal, Hatice Özer, Sema Arici, Kamali Gh, Selma Sengiz Erhan, Meral Koyuncuoglu, Akbulut M, Kahraman Ds, Hulya Dogan, Çelik B, Kimiloğlu E, Alp Usubutun, Kivilcim Eren Erdogan, Şahin N, Safak Ersoz, Demir H, Emine Kilic Bagir, Erdoğan G, Mehmet Kefeli, Yılmaz Baş, Abdullah Aydin, Asli Cakir, Astarci M, Tulin Yalta, Serdar Altınay, Iclal Gurses, Çetiner H, Nuray Başsüllü, Funda Eren, Bolat Fa, Yasemin Yuyucu Karabulut, Sevinç Şahin, Bengü Çobanoğlu, Aslan F, Bahar Muezzinoglu, Nihan Haberal, Sevgen Onder, Resit Dogan Koseoglu, Omer Murat Aydin, Özcan Z, Pinar Firat, İlknur Türkmen, Sönmez Fc, OMÜ, BAİBÜ, Tıp Fakültesi, Cerrahi Tıp Bilimleri Bölümü, Astarcı, Müzeyyen, Çukurova Üniversitesi, Acibadem University Dspace, Hitit Üniversitesi, Tıp Fakültesi, Cerrahi Tıp Bilimleri Bölümü, ARICI, DILEK SEMA, ŞAHİN, NURHAN, and Çetinaslan Türkmen, İ., Department of Pathology, Istanbul Medipol University Faculty of Medicine, İstanbul, Turkey -- Usubütün, A., Department of Pathology, Hacettepe University Faculty of Medicine, Ankara, Turkey -- Çakir, A., Department of Pathology, Istanbul Medipol University Faculty of Medicine, İstanbul, Turkey -- Aydin, Ö., Department of Pathology, Acibadem University Faculty of Medicine, İstanbul, Turkey -- Aka Bolat, F., Department of Pathology, Başkent University ERH, Adana, Turkey -- Akbulut, M., Department of Pathology, Pamukkale University Faculty of Medicine, Denİzlİ, Turkey -- Altinay, S., Department of Pathology, Bagcilar ERH, Istanbul, Turkey -- Arici, S., Department of Pathology, Bezmialem Vakif University Faculty of Medicine, Istanbul, Turkey -- Aslan, F., Department of Pathology, Dumlupinar University Evliya Celebi ERH, KÜtahya, Turkey -- Astarci, M., Department of Pathology, Abant Izzet Baysal University Faculty of Medicine, Bolu, Turkey -- Kılıç Bağir, E., Department of Pathology, Cukurova University Faculty of Medicine, Adana, Turkey -- Baş, Y., Department of Pathology, Hitit University Çorum ERH, Çorum, Turkey -- Başsüllü, N., Department of Pathology, Bilim University Faculty of Medicine, Istanbul, Turkey -- Çelik, B., Department of Pathology, Antalya ERH, Antalya, Turkey -- Çetiner, H., Department of Pathology, Zeynep Kamil ERH, İstanbul, Turkey -- Çobanoğlu, B., Department of Pathology, Medeniyet University Goztepe ERH, İstanbul, Turkey -- Aydin, A., Department of Pathology, Medeniyet University Goztepe ERH, İstanbul, Turkey -- Demir, H., Department of Pathology, Istanbul University Cerrahpaşa Medical Faculty, İstanbul, Turkey -- Tatlı Doğan, H., Department of Pathology, Yildirim Beyazit University Ankara Ataturk ERH, Ankara, Turkey -- Gülçin Eken, K., Department of Pathology, Sisli Hamidiye Etfal ERH, İstanbul, Turkey -- Şengiz Erhan, S., Department of Pathology, Okmeydani ERH, İstanbul, Turkey -- Erdoğan, G., Department of Pathology, Akdeniz University Faculty of Medicine, Antalya, Turkey -- Eren Erdoğan, K., Department of Pathology, Mersin State Hospital, Mersİn, Turkey -- Eren, F., Department of Pathology, Marmara University Faculty of Medicine, İstanbul, Turkey -- Ersöz, Ş., Department of Pathology, Karadeniz Technical University Faculty of Medicine, Trabzon, Turkey -- Firat, P., Department of Pathology, Istanbul University Faculty of Medicine, İstanbul, Turkey -- Gürses, İ., Department of Pathology, Mersin University Faculty of Medicine, Mersİn, Turkey -- Haberal, N., Department of Pathology, Baskent University Faculty of Medicine, Ankara, Turkey -- Solakoğlu Kahraman, D., Department of Pathology, Tepecik ERH, İZMİR, Turkey -- Kamali, G.H., Department of Pathology, Okmeydani ERH, İstanbul, Turkey -- Karabulut, Y.Y., Department of Pathology, Cankiri State Hospital, Çankiri, Turkey -- Kefeli, M., Department of Pathology, Ondokuz Mayis University Faculty of Medicine, Samsun, Turkey -- Koyuncuoğlu, M., Department of Pathology, Dokuz Eylul University Faculty of Medicine, İzmİr, Turkey -- Köseoğlu, R.D., Department of Pathology, Gaziosmanpasa University Faculty of Medicine, Tokat, Turkey -- Müezzinoğlu, B., Department of Pathology, Kocaeli University Faculty of Medicine, Kocaelİ, Turkey -- Onal, B., Department of Pathology, Diskapi ERH, Ankara, Turkey -- Önder, S., Department of Pathology, Hacettepe University Faculty of Medicine, Ankara, Turkey -- Özcan, Z., Department of Pathology, Taksim ERH, İstanb, UL, Turkey -- Kimiloğlu, E., Department of Pathology, Taksim ERH, İstanb, UL, Turkey -- Özer, H., Department of Pathology, Cumhuriyet University Faculty of Medicine, Sİvas, Turkey -- Sönmez, F.C., Department of Pathology, Bezmialem Vakif University Faculty of Medicine, Istanbul, Turkey -- Şahin, S., Department of Pathology, Bozok University Faculty of Medicine, Yozgat, Turkey -- Şahin, N., Department of Pathology, Inonu University Faculty of Medicine, Malatya, Turkey -- Yalta, T., Department of Pathology, Trakya University Faculty of Medicine, Edİrne, Turkey

Subjects
0301 basic medicine, Turkey, hematologic disease, Uterine Cervical Neoplasms, cytotechnologist, Medical Oncology, Turkey (republic), uterine cervix tumor, Control parameters, Early Detection of Cancer, early cancer diagnosis, media_common, medicine.diagnostic_test, uterine cervix dysplasia, Obstetrics, Papanicolaou test, Squamous intraepithelial lesion, female, uterine cervix cytology, oncology, standards, lcsh:RB1-214, Quality Control, medicine.medical_specialty, uterine cervix biopsy, media_common.quotation_subject, 030106 microbiology, uterine cervix carcinoma, Atypical Squamous Cells, Epithelial cell abnormality, Article, Pathology and Forensic Medicine, 03 medical and health sciences, lcsh:Pathology, medicine, Humans, Quality (business), human, Pap test, Vaginal Smears, business.industry, questionnaire, squamous intraepithelial lesion of the cervix, Cervical cytology, medicine.disease, Cervical Smear, Surgery, Cervical smear, business, Quality assurance, vagina smear
Abstract

Erdogan, Kivilcim Eren/0000-0002-4951-8703; kilic bagir, Emine/0000-0002-1447-1060; Celik, Betul/0000-0001-9731-9939; Tatli Dogan, Hayriye/0000-0003-4318-2775; Cakir, Asli/0000-0003-0128-6947 WOS: 000414649400006 PubMed: 28272675 Objective: There is no other screening program close to the success rate of PAP test. Cervical cytology constitutes a large workload so that quality control in cervical cytology is important for the quality assurance of pathology laboratories. Material and Method: In this study, we collected the cervical cytology results from all over Turkey and discussed the parameters influencing the quality of the PAP test. The study was conducted with Turkish gynaecopathology working group and 38 centers (totally 45 hospitals) agreed to contribute from 24 different cities. The study was designed to cover the cervical cytology results during 2013. The results were evaluated from the data based on an online questionnaire. Results: The total number of Epithelial Cell Abnormality was 18,020 and the global Epithelial Cell Abnormality rate was 5.08% in the total 354,725 smears and ranging between 0.3% to 16.64% among centers. The Atypical squamous cells/Squamous intraepithelial lesion ratios changed within the range of 0.21-13.94 with an average of 2.61. When the centers were asked whether they performed quality assurance studies, only 14 out of 28 centers, which shared the information, had such a control study and some quality parameters were better in these centers. Conclusion: There is an increase in the global Epithelial Cell Abnormality rate and there are great differences among centers. Quality control studies including the Atypical squamous cells/Squamous intraepithelial lesion ratio are important. Corrective and preventive action according to quality control parameters is a must. A cervical cytology subspecialist in every center can be utopic but a dedicated pathologist in the center is certainly needed.

Published
2017

4. The Relationship Between DNA Mismatch Repair Status and Clinicopathologic Characteristics in Colon Cancer.

Author

Doğan M, Kılıç M, and Tatlı Doğan H

Subjects
Humans, Male, Female, Retrospective Studies, Middle Aged, Aged, Adult, DNA-Binding Proteins genetics, MutS Homolog 2 Protein genetics, MutS Homolog 2 Protein metabolism, Aged, 80 and over, Mismatch Repair Endonuclease PMS2 genetics, DNA Mismatch Repair genetics, Microsatellite Instability, Proto-Oncogene Proteins B-raf genetics, Colonic Neoplasms genetics, Colonic Neoplasms pathology, MutL Protein Homolog 1 genetics, Immunohistochemistry, Colorectal Neoplasms, Hereditary Nonpolyposis genetics, Colorectal Neoplasms, Hereditary Nonpolyposis pathology, Mutation
Abstract

DNA mismatch repair (MMR) proteins are essential for repairing genetic mutations that occur during DNA replication. Deficiency of MMR proteins results in a phenotype called microsatellite instability (MSI), which occurs in Lynch syndrome as well as sporadic colorectal cancers (CRC), and it is associated with several clinicopathological features. We aimed to investigate the association of the loss of MMR proteins with clinicopathologic considerations in our CRC series. In this retrospective study, DNA MMR protein status in CRC is evaluated in a total of 200 colorectal resection specimens by immunohistochemistry (IHC) for MLH1, MSH2, MSH6 and PMS2 protein expression. The BRAF mutation was investigated by the real-time PCR in cases with loss of MLH1 protein expression. The relationship between MMR status and clinicopathological parameters was investigated statistically. Loss of MMR protein expression was detected in 26 of 200 CRC cases. The BRAFV600E mutation was detected in 2 of the cases with MLH1 loss and accepted as sporadic. The remaining 24 cases (12%) were identified as Lynch syndrome candidates. There were statistical differences observed regarding the presence of tumor-infiltrating lymphocytes (P < .001), Crohn's-like reaction (P = .001), expansile growth (P < .001), tumor heterogeneity (P < .001), mucinous differentiation (P < .001), and presence of metastatic lymph nodes (P = .045) between sporadic cases with preserved MMR and Lynch candidates. However, difference in the survival rates between sporadic cases and Lynch candidates was not significant. Immunohistochemical staining for MMR is a practical method for predicting MSI phenotype as well as Lynch candidates. MMR expression status was found to be associated with certain clinicopathological features some of which also have prognostic significance.

Published
2024
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5. Lysyl Oxidase Like-4 (LOXL4) as a tumor marker and prognosticator in advanced stage laryngeal cancer.

Author

Altuntaş OM, Süslü N, Güler Tezel YG, Tatlı Doğan H, and Yılmaz T

Subjects
Humans, Biomarkers, Tumor metabolism, Laryngectomy, Neoplasm Staging, Laryngeal Neoplasms diagnosis, Laryngeal Neoplasms metabolism, Protein-Lysine 6-Oxidase metabolism, Squamous Cell Carcinoma of Head and Neck diagnosis, Squamous Cell Carcinoma of Head and Neck metabolism
Abstract

Introduction: Lysyl oxidase-like 4 is an amine oxidase from the lysyl oxidase family that was previously shown to be overexpressed in head and neck cancer and upregulated in response to hypoxia. The possible role of lysyl oxidase-like 4 as a tumor marker in advanced stage larynx cancer was investigated., Objective: To investigate the expression of lysyl Oxidase-Like 4 protein in advanced stage laryngeal cancer and elucidate its possible role as a tumor marker, predictor of treatment response and prognosticator., Methods: Diagnostic specimens of 72 patients treated for stage III-IV laryngeal squamous cell carcinoma were evaluated for lysyl oxidase-like 4 expression by immunohistochemistry., Results: Lysyl oxidase-like 4 expression was correlated with advanced tumor stage (p = 0.041) and better differentiation (p = 0.025) but was independent of tumor diameter (p = 0.456). Response to induction chemotherapy or the need for salvage laryngectomy were not affected by lysyl oxidase-like 4 expression (p = 0.999, p = 0.070 respectively). Increased lysyl oxidase-like 4 expression was associated with better 2 year overall survival in both univariate (p = 0.036) and multivariate analyses (p = 0.014)., Conclusion: Lysyl oxidase-like 4 expression emerges with advancing stages, is lost with worsening differentiation, and may have tumor suppressive properties in larynx cancer., (Copyright © 2021 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.)

Published
2022
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6. Retrospective analysis of oncogenic human papilloma virus and Epstein-Barr virus prevalence in Turkish nasopharyngeal cancer patients.

Author

Tatlı Doğan H, Kılıçarslan A, Doğan M, Süngü N, Güler Tezel G, and Güler G

Subjects
Adult, Aged, Carcinoma, Female, Humans, Immunohistochemistry, In Situ Hybridization, Kaplan-Meier Estimate, Male, Middle Aged, Nasopharyngeal Carcinoma, Nasopharyngeal Neoplasms mortality, Prevalence, Retrospective Studies, Turkey, Young Adult, Epstein-Barr Virus Infections epidemiology, Nasopharyngeal Neoplasms virology, Papillomavirus Infections epidemiology
Abstract

Nasopharyngeal carcinoma (NPC) is associated with the Epstein-Barr virus (EBV). Human papilloma virus (HPV) has also been detected in NPC cases. In this retrospective study, we analyze the frequency of EBV and HPV infection in 82 Turkish patients with NPC. A total of 82 were evaluated for EBV and HPV. In situ hybridization (ISH) was performed for EBV. HPV-ISH and P16 immunohistochemistry used to determine the HPV status. Seventy-two of the 82 (87%) NPC patients were EBV-positive. The highest rate of EBV-positivity was found in undifferentiated NPC patients, which accounted for 65 of 68 (95.6%) undifferentiated cases. One of the 82 NPC patients whose tumor was non-keratinizing differentiated, contained HPV. Our data shows that EBV is closely associated with NPC in Turkey. We found lower rates of HPV-positivity in NPC patients than in North American populations. In addition, both EBV and HPV-negativity were more associated with decreased survival than EBV-positive cases., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

Published
2016
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