Screening of cytochrome CYP26A1 expression in different bone tumors

Cytochrome P450 26A1 (CYP26A1) is a retinoic acid metabolizing enzyme which is overexpressed in many cancers. However, its expression in bone tumors has not been characterized. Immunohistochemistry was used to evaluate CYP26A1 expression in a human bone disease spectrum comprising duplicated cores of 95 cases of benign, intermediate and malignant bone tumors alongside normal bone samples. STRING database was utilized to perform CYP26A1 protein–protein interaction and functional enrichment analyses. CYP26A1 staining was not identified in the normal bone samples analyzed. Collectively, CYP26A1 was expressed in 31.6% (30/95) of bone tumors, with cytoplasmic localization, while no immunoreactivity was detected in normal tissues. Compared with benign (18.8%) and malignant tumors (27.1%), intermediate bone tumors expressed CYP26A1 significantly more frequently (66.7%). This difference in expression between tumor categories was statistically confirmed ( p < 0.05, Cramér’s V = 0.382). Among intermediate tumors, CYP26A1 was detected with high frequency and weak staining intensity in giant cell tumors (GCTs, 14/20 cases), with immunoreactivity localized mainly in osteoblast-like and osteocyte-like stromal cells. Malignant bone tumors predominantly showed focal or an absence of CYP26A1 immunoreactivity. However, strong CYP26A1 immunoreactivity was displayed in the limited chordoma and adamantinoma cases examined, while osteosarcoma and Ewing sarcoma displayed no immunoreactivity in general. Interestingly, functional enrichment analysis confirmed the established association of CYP26A1 with retinoid metabolic pathways. CYP26A1 expression was most frequent in giant cell tumors of bone. While also detected in a subset of other bone tumors, expression was limited or absent in most benign and malignant lesions, and entirely absent in normal bone tissue. These findings provide novel descriptive insight into CYP26A1 distribution and support further investigation into its role in retinoid-related pathways in bone tumor biology.