Abstract
Background Karyopherin α 2 (KPNA2), a member of the Karyopherin α family, has been observed in several cancers but lack substantial investigation in malignant bone tumors. The purpose of the current study was to evaluate KPNA2 expression level and its utility as a novel diagnostic biomarker in osteosarcomas and their malignant bone tumor mimickers, such as chondrosarcomas and Ewing sarcomas.Method We investigated the expression of KPNA2 protein by immunohistochemistry on paraffin embedded surgical specimens from 217 patients with malignant and benign tumors of bone, including 81 osteosarcomas, 42 chondrosarcomas, 9 Ewing sarcomas, 28 osteoid osteoma, 20 osteochondroma and 37 Chondroblastoma. Immunoreactivity was scored semi quantitatively based on stain extent and intensity.Results Seventy one of 81 (87.7%) osteosarcomas, zero of 42 (0%) chondrosarcomas and one of 9 (11.1%) Ewing sarcomas showed immunoreactivity for KPNA2. Negative KPNA2 expression was observed in all of benign bone tumors. Much more positive expression of KPNA2 was found in osteosarcomas as compared with chondrosarcomas and Ewing sarcomas. The sensitivity and specificity of KPNA2 immuno-expression for osteosarcoma was 87.7% and 100%, respectively. In several subtypes of osteosarcomas, immunohistochemical expression of KNA2 was more frequent in osteoblastic (94.5%), with 39 (70.9%) showing strong-intensity staining. KPNA2 positivity was observed in eleven of 13 (84.6%) chondroblastic, three of 6 (50%) fibroblastic, three of 4 (75%) telangiectatic and two of 3 (66.7%) giant cell-rich osteosarcoma. Stronger-intensity staining was observed in osteoblastic osteosarcoma.Conclusion KPNA2 is most frequently expressed in osteosarcomas, particularly in osteoblastic and chondroblastic tumors, but is rarely positive in chondrosarcomas and Ewing sarcomas. This feature may have diagnostic value since it is very useful for distinguishing between osteosarcomas and other bone sarcomas mimickers. This report supports KPNA2 as a novel marker for the diagnosis of osteosarcoma.
KPNA2 expression is a potential marker for differential diagnosis between osteosarcomas and other malignant bone tumor mimickers
