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Simple Summary  Amplification and overexpression of the  SEC62  oncogene was reported in a variety of human cancers and was associated with poor prognosis as well as lymph node and distant metastases. In this study,  SEC62  expression was analyzed in benign, borderline, and malignant melanocytic lesions of 209 patients. We found the highest expression in Spitz nevi, followed by melanoma metastases, primary melanoma, congenital nevi, and blue nevi. In melanoma patients, high Sec62 levels correlated with shorter overall and progression-free survival. Significantly higher Sec62 levels were found in melanomas with lymph node and distant metastases compared with those without. Taken together, these data suggest a relevant role of  SEC62  as a metastasis-stimulating oncogene in melanoma development, which represents a promising therapeutic target.    Abstract   SEC62  oncogene located at chromosomal region 3q26 encodes for a transmembrane protein of the endoplasmic reticulum (ER) and is expressed at high levels in numerous human malignancies.  SEC62  overexpression has been associated with worse prognosis and high risk for lymphatic and distant metastases in head and neck cancer, cervical cancer, hepatocellular cancer, and lung cancer. However, its role in the development and tumor biology of melanocytic lesions has not been investigated so far. An immunohistochemical study including 209 patients with melanocytic lesions (malignant melanoma (MM),  n  = 93; melanoma metastases (MET),  n  = 28; Spitz nevi (SN),  n  = 29; blue nevi (BN),  n  = 21; congenital nevi (CN),  n  = 38) was conducted and  SEC62  expression was correlated with clinical data including patient survival and histopathological characteristics. SN showed the highest  SEC62  expression levels followed by MET, MM, CN, and BN. High  SEC62  expression correlated with a shorter overall and progression-free survival in MM patients. Additionally, high Sec62 levels correlated significantly with higher tumor size (T stage), the presence of tumor ulceration, and the presence of lymph node as well as distant metastases. Strikingly,  SEC62  expression showed a strong correlation with Clark level. Taken together, these data demonstrate that  SEC62  is a promising prognostic marker in MM and has the potential to predict biological behavior and clinical aggressiveness of melanocytic lesions.

Expression of SEC62 Oncogene in Benign, Malignant and Borderline Melanocytic Tumors—Unmasking the Wolf in Sheep’s Clothing?