Differential HLA class I subunit (A, B, C heavy chain and β₂-microglobulin) expression levels in normal tissues

Human leukocyte antigen (HLA) class I subunit expression level in primary and metastatic lesions has been characterized in many cancer types utilizing formalin-fixed and paraffin-embedded (FFPE) tissue sections as substrates in immunohistochemical reactions. The evaluation of the results of these studies has been hampered by the scant information about HLA class I subunit expression level in normal tissues. To address this unmet need, we have analyzed the HLA class I subunit expression level in FFPE sections of normal tissues.Two tissue microarray (TMA) blocks were constructed from archived FFPE tissue samples of a wide number of human normal tissues. The expression level of HLA-A, HLA-B, HLA-C heavy chains and β2-microglobulin (β2-M) was evaluated by IHC staining, with mAb HC-A2, mAb HC-10, and mAb NAMB1, respectively. The staining was scored according to its intensity.According to their staining patterns with the three mAbs tested, normal tissues can be divided into four groups: (i) tissues displaying moderate/strong staining patterns, (ii) tissues displaying barely detectable staining patterns, (iii) tissues displaying differential staining patterns, and (iv) tissues with no detectable staining. The ubiquitous expression pattern for HLA-A, B, C heavy chain and β2-M was found only at the endothelial level; the stroma was negative except for fibroblasts in all the tissues analyzed. Our data suggest that, contrary to the general postulate, HLA class I subunit expression is not detectable in all nucleated cells. This information provides a useful background to evaluate changes in HLA class I subunit expression associated with the malignant transformation of cells.