Report Significance of SOX18 expression in nonmelanoma skin cancers for prediction of high-risk patients: a preliminary study Yomna Mazid El-Hamd Neinaa 1 , MD, Amal Ahmad El-Ashmawy 1 , MD, Hanan Al-Saeid Alshenawy 2 , MD and Enas Elsaid Ahmed Arakeeb 3 , MSc 1 Dermatology and Venereology, Faculty of Medicine, Tanta University, Tanta, Egypt, 2 Pathology, Faculty of Medicine, Tanta University, Tanta, Egypt, and 3 Dermatology and Venereology, Mahalet Marhom General Hospital, Tanta, Egypt Correspondence Yomna Mazid El-Hamd Neinaa, MD Assistant Professor of Dermatology & Venereology Faculty of Medicine Tanta University Tanta, Egypt E-mail: yomnamazid@yahoo.com Conflict of interest: None. Funding source: None. doi: 10.1111/ijd.15032 Abstract Background SOX18 is an integral transcription factor that is involved in endothelial cells differentiation during both angiogenesis and lymphangiogenesis. Therefore, it has been implicated in tumor progression and metastasis. Objective To study SOX18 expression in nonmelanoma skin cancers (NMSCs) in comparison to seborrheic keratosis (SK) and normal control skin, and to assess its probable role in tumor evolution and progression. Patients and Methods This study was conducted on 60 specimens of NMSCs: 30 basal cell carcinomas (BCC) and 30 squamous cell carcinomas (SCC), 30 specimens of SK, and 30 normal skin specimens. All were examined for immunohistochemical expression of SOX18 antibody. Additionally, morphometric assessment of vessel density (blood & lymphatic) in each specimen was estimated. Results Significant SOX18 overexpression was observed in all studied cutaneous tumors in comparison to control skin. The highest score of SOX18 expression was detected in SCC, then BCC, and the least expression was reported in SK with significant difference between them. Furthermore, significant upregulation of SOX18 expression was observed in high-risk types of both BCC and SCC compared to low-risk types. Stromal vessel density showed significant differences between the studied tumors with the highest mean value in SCC, followed by BCC and then SK. Positive correlation between SOX18 expression in the studied tumors and their vessel density was detected. Conclusions SOX18 may have a potential role in the evolution as well as progression of NMSCs, possibly through induction of both angiogenesis and lymphangiogenesis. Furthermore, it could be beneficial for prediction of NMSC patients with poor prognosis. Introduction Nonmelanoma skin cancers (NMSCs), including basal cell carci- noma (BCC) and squamous cell carcinoma (SCC), are reported to be increasing in incidence worldwide. Both are capable of locally infiltrative growth and metastatic spread, although the incidence of metastases from BCC is very low. However, SCC is characterized by its liability to spread to regional lymph nodes and distant metastasis. Seborrheic keratosis (SK) is the com- monest benign epidermal neoplasm. They do not specify a major health concern, unless developed abruptly. 1-3 The SOX genes are defined as the high mobility group (HMG)-box genes involved in sex determination called SRY, which resides on Y-chromosomes. Based on their amino acid homology, members of the SOX family have been divided into 10 groups (A–J). 4 SOX18 belongs to group F and is involved in maturation and differentiation of endothelial cells prenatally and in angiogenesis 5 and lymphangiogenesis postnatally. 6 Recent studies detected upregulation of SOX18 in various kinds of human neoplasm and suggested that it may have an oncogenic role in tumor promotion and progression. 7-10 However, its contri- bution in NMSCs is not yet elucidated. Therefore, it is considered interesting to study the immuno- histochemical expression of SOX18 in NMSCs (BCC and SCC) compared to SK (as a benign skin neoplasm) and normal skin (as a healthy control) to assess its potential role in their evolu- tion and progression. Patients and methods This study was a prospective, case–control study, carried out on 120 skin specimens classified as follows: Group I: 30 normal control skin specimens obtained from healthy subjects, matched to patients as regards age and sex. Group ΙΙ: 30 SK specimens, ª 2020 the International Society of Dermatology International Journal of Dermatology 2020 1