DNA methylation is an essential component of epigenetic modification. Global genome hypomethylation in cancer cells can lead to chromosomal instability and activate endogenous elements, including long interspersed nuclear elements-1(LINE-1). LINE-1 is recognised as a useful surrogate marker of whole-genome methylation levels, encoding two proteins: open reading frame (ORF)1 and ORF2. Various types of internal organ cancers have been reported to show immunoreactivity to LINE-1 ORF1 protein. However, the expression of LINE-1 protein in skin tumors has not been investigated yet. In this study, we examined LINE-1 expression in skin tumors as well as normal skin.
A total of 120 formalin-fixed and paraffin-embedded samples of malignant and benign skin tumors were examined immunohistochemically using an anti-LINE-1 ORF1p antibody. Genomic DNA was extracted from the samples, and a DNA methylation analysis for the LINE-1 promoter region was carried out by pyrosequencing (PyroMark Q24 CpG LINE-1) three cases of each tumor.
In normal skin, LINE-1 was expressed only in the hair follicles and sebaceous glands. Among skin tumors, basal cell carcinoma (BCC) (100%), squamous cell carcinoma (SCC) (81%), Bowen’s disease (91%) and malignant melanoma (MM) (18%) revealed positivity to LINE-1. LINE-1 promoter methylation was reduced in BCC (56%; average of 3cases) and SCC (52.6%) compared to normal skin (73%).
High rates of positivity for anti-LINE-1 ORF1p antibody were generally seen in malignant skin tumors.  Our results suggest that LINE-1 hypomethylation may generally occur in malignant skin tumors and LINE-1 may be a useful surrogate marker for global hypomethylation.

Long interspersed nuclear elements-1 expression in skin tumors