As the HEp-2 cells are derived from a human adenocarcinoma, and as the location of HMGB1 may predominate in the cytoplasm of malignant cells [45, 46], this could be a plausible explanation for the cytoplasmic staining of HMGB1 in HEp-2 cells. This evidence concerns the gene HMGB1 and adenocarcinoma.