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Current Advances on Non-Melanoma Skin Cancer • Constantin Caruntu Current Advances on Non-Melanoma Skin Cancer

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Current Advances on Non-Melanoma Skin Cancer • Constantin Caruntu Current Advances on Non-Melanoma Skin Cancer Current Advances on Non-Melanoma on Cancer Skin Advances Current • Constantin Caruntu Current Advances on Non-Melanoma Skin Cancer Edited by Constantin Caruntu Printed Edition of the Special Issue Published in Journal of Clinical Medicine www.mdpi.com/journal/jcm Current Advances on Non-Melanoma Skin Cancer Current Advances on Non-Melanoma Skin Cancer Editor Constantin Caruntu MDPI • Basel • Beijing • Wuhan • Barcelona • Belgrade • Manchester • Tokyo • Cluj • Tianjin Editor Constantin Caruntu “Carol Davila” University of Medicine and Pharmacy Romania Editorial Office MDPI St. Alban-Anlage 66 4052 Basel, Switzerland This is a reprint of articles from the Special Issue published online in the open access journal Journal of Clinical Medicine (ISSN 2077-0383) (available at: https://www.mdpi.com/journal/jcm/ special issues/Non-Melanoma Skin Cancer). For citation purposes, cite each article independently as indicated on the article page online and as indicated below: LastName, A.A.; LastName, B.B.; LastName, C.C. Article Title. Journal Name Year, Volume Number, Page Range. ISBN 978-3-0365-0890-0 (Hbk) ISBN 978-3-0365-0891-7 (PDF) © 2021 by the authors. Articles in this book are Open Access and distributed under the Creative Commons Attribution (CC BY) license, which allows users to download, copy and build upon published articles, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. The book as a whole is distributed by MDPI under the terms and conditions of the Creative Commons license CC BY-NC-ND. Contents About the Editor .............................................. vii Preface to ”Current Advances on Non-Melanoma Skin Cancer” .................. ix Taxiarchis Konstantinos Nikolouzakis, Luca Falzone, Konstantinos Lasithiotakis, Sabine Kr uger-Krasagakis,¨ Alexandra Kalogeraki, Maria Sifaki, Demetrios A. Spandidos, Emmanuel Chrysos, Aristidis Tsatsakis and John Tsiaoussis Current and Future Trends in Molecular Biomarkers for Diagnostic, Prognostic, and Predictive Purposes in Non-Melanoma Skin Cancer Reprinted from: J. Clin. Med. 2020, 9, 2868, doi:10.3390/jcm9092868 ................. 1 Mircea Tampa, Simona Roxana Georgescu, Cristina Iulia Mitran, Madalina Irina Mitran, Clara Matei, Cristian Scheau, Carolina Constantin and Monica Neagu Recent Advances in Signaling Pathways Comprehension as Carcinogenesis Triggers in Basal Cell Carcinoma Reprinted from: J. Clin. Med. 2020, 9, 3010, doi:10.3390/jcm9093010 ................. 23 Paola Pasquali, Gonzalo Segurado-Miravalles, Mar Castillo, Angeles´ Fortu ˜no,Susana Puig and Salvador Gonz´alez Use of Cytology in the Diagnosis of Basal Cell Carcinoma Subtypes Reprinted from: J. Clin. Med. 2020, 9, 612, doi:10.3390/jcm9030612 ................. 39 Mihai Lupu, Iris Maria Popa, Vlad Mihai Voiculescu, Ana Caruntu and Constantin Caruntu A Systematic Review and Meta-Analysis of the Accuracy of in Vivo Reflectance Confocal Microscopy for the Diagnosis of Primary Basal Cell Carcinoma Reprinted from: J. Clin. Med. 2019, 8, 1462, doi:10.3390/jcm8091462 ................. 49 Andreea D. Lazar, Sorina Dinescu and Marieta Costache Deciphering the Molecular Landscape of Cutaneous Squamous Cell Carcinoma for Better Diagnosis and Treatment Reprinted from: J. Clin. Med. 2020, 9, 2228, doi:10.3390/jcm9072228 ................. 67 Ricardo Moreno, Laura N´ajera,Marta Mascaraque, Angeles´ Juarranz, Salvador Gonz´alezand Yolanda Gilaberte Influence of Serum Vitamin D Level in the Response of Actinic Keratosis to Photodynamic Therapy with Methylaminolevulinate Reprinted from: J. Clin. Med. 2020, 9, 398, doi:10.3390/jcm9020398 ................. 91 Mihai Lupu, Ana Caruntu, Daniel Boda and Constantin Caruntu In Vivo Reflectance Confocal Microscopy-Diagnostic Criteria for Actinic Cheilitis and Squamous Cell Carcinoma of the Lip Reprinted from: J. Clin. Med. 2020, 9, 1987, doi:10.3390/jcm9061987 .................101 v About the Editor Constantin Caruntu (MD, Ph.D.) is professor of Physiology at the “Carol Davila” University of Medicine and Pharmacy and is also a dermatologist at the “Prof. N. Paulescu” National Institute of Diabetes in Bucharest. He is trained in in vivo reflectance confocal microscopy, cellular and molecular biology techniques, and molecular imaging techniques. He is member of the International Dermoscopy Society, International League of Dermatological Societies, International Union of Physiological Sciences and many other national or international scientific societies. Furthermore, he is academic editor, guest editor and reviewer for various prestigious scientific journals. His research interests include in vivo reflectance confocal microscopy, dermato-oncology, inflammatory skin diseases, neurogenic inflammation and neuroendocrinology of the skin. vii Preface to ”Current Advances on Non-Melanoma Skin Cancer” Non-melanoma skin cancer (NMSC) comprises basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and several rare skin tumors and is the most common malignancy that affects humans worldwide. It accounts for the vast majority of skin cancers and a large percentage of all malignant tumors. Despite the growing public awareness and scientific interest regarding the risk of skin cancer, the incidence of NMSC is still rapidly increasing. Even if most NMSCs are associated with a less aggressive behavior, they can still be locally invasive and may produce extensive destruction of neighboring structures, inducing significant morbidity. Moreover, different types or subtypes of NMSCs are associated with frequent recurrence and may carry a significant metastatic potential. As a direct consequence, NMSC has become a major burden on healthcare systems with a significant socio-economic impact. Hence, there is no doubt as to why these keratinocyte-derived tumors are in the spotlight of scientific interest for both fundamental research and clinical practice. Consequently, this Special Issue brings together recent and relevant scientific research on NMSC. Studies regarding the complex inherited and environmental factors that can trigger tumor initiation and progression may offer a new perspective on skin cancer prevention. Investigation of new markers of skin carcinogenesis may contribute to the development of novel diagnostic, staging, and prognosis strategies for skin cancer and could lead to the design of more sophisticated and individually tailored treatment protocols. Improvements related to non-invasive or minimally invasive diagnostic tools and treatment methods may ameliorate the discomfort of patients while also reducing the costs associated with therapy. Moreover, the development of new techniques for the early diagnosis of NMSCs could reduce morbidity, ensuring more efficient treatment with better aesthetic and functional results. Constantin Caruntu Editor ix Journal of Clinical Medicine Review Current and Future Trends in Molecular Biomarkers for Diagnostic, Prognostic, and Predictive Purposes in Non-Melanoma Skin Cancer Taxiarchis Konstantinos Nikolouzakis 1,2, Luca Falzone 3, Konstantinos Lasithiotakis 2, Sabine Krüger-Krasagakis 4, Alexandra Kalogeraki 5, Maria Sifaki 6, Demetrios A. Spandidos 7, Emmanuel Chrysos 2, Aristidis Tsatsakis 6,* and John Tsiaoussis 1,* 1 Laboratory of Anatomy-Histology-Embryology, Medical School, University of Crete, 71110 Heraklion, Crete, Greece; [email protected] 2 Department of General Surgery, University General Hospital of Heraklion, 71110 Heraklion, Crete, Greece; [email protected] (K.L.); [email protected] (E.C.) 3 Epidemiology Unit, IRCCS Istituto Nazionale Tumori ‘Fondazione G. Pascale’, I-80131 Naples, Italy; [email protected] 4 Dermatology Department, University Hospital of Heraklion, 71110 Heraklion, Crete, Greece; [email protected] 5 Department of Pathology-Cytopathology, Medical School, University of Crete, 70013 Heraklion, Crete, Greece; [email protected] 6 Centre of Toxicology Science and Research, Faculty of Medicine, University of Crete, 71003 Heraklion, Crete, Greece; [email protected] 7 Laboratory of Clinical Virology, Medical School, University of Crete, 71003 Heraklion, Crete, Greece; [email protected] * Correspondence: [email protected] (A.T.); [email protected] (J.T.) Received: 3 August 2020; Accepted: 1 September 2020; Published: 4 September 2020 Abstract: Skin cancer represents the most common type of cancer among Caucasians and presents in two main forms: melanoma and non-melanoma skin cancer (NMSC). NMSC is an umbrella term, under which basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and Merkel cell carcinoma (MCC) are found along with the pre-neoplastic lesions, Bowen disease (BD) and actinic keratosis (AK). Due to the mild nature of the majority of NMSC cases, research regarding their biology has attracted much less attention. Nonetheless, NMSC can bear unfavorable characteristics for the patient, such as invasiveness, local recurrence and distant metastases. In addition, late diagnosis is relatively common for a number of cases of NMSC due to the inability to recognize such cases. Recognizing the need for clinically and economically efficient modes of diagnosis, staging, and prognosis, the present review discusses the main etiological and pathological features of NMSC as well as the new and promising molecular biomarkers available including telomere length (TL), telomerase activity (TA), CpG island methylation (CIM), histone methylation and acetylation, microRNAs (miRNAs), and micronuclei frequency (MNf). The
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