KPNA2 expression is a potential marker for differential diagnosis between osteosarcomas and other malignant bone tumor mimics

Background: Karyopherin α2 (KPNA2), a member of the karyopherin α family, has been studied in several cancers but has not yet been substantially investigated in malignant bone tumors. The purpose of the current study was to evaluate the KPNA2 expression level and its utility as a novel diagnostic biomarker in osteosarcomas and malignant bone tumor mimics, such as chondrosarcomas and Ewing sarcomas (ESs). Method: We investigated the expression of KPNA2 protein by immunohistochemistry on paraffin-embedded surgical specimens from 223 patients with malignant and benign bone tumors, including 81 osteosarcomas, 42 chondrosarcomas, 15 ESs, 28 osteoid osteomas, 20 osteochondromas and 37 chondroblastomas. Immunoreactivity was scored semiquantitatively based on staining extent and intensity. Results: Sixty-seven of 81 (82.7%) osteosarcoma, zero of 42 (0%) chondrosarcoma and one of 15 (6.7%) ES samples showed immunoreactivity for KPNA2. Negative KPNA2 expression was observed in all benign bone tumors. The expression of KPNA2 in osteosarcoma samples was much higher than that in chondrosarcoma and ES samples ( P <0.001). The sensitivity and specificity of KPNA2 immunoexpression for detecting osteosarcoma were 82.7% and 100%, respectively. Several subtypes of osteosarcoma were analyzed, and immunostaining of KPNA2 was frequent in osteoblastic samples (90.9%), with 39 samples (70.9%) showing strong-intensity staining. KPNA2 positivity was observed in ten of 13 (76.9%) chondroblastic, two of 6 (33.3%) fibroblastic, three of 4 (75%) telangiectatic and two of 3 (66.7%) giant cell-rich osteosarcoma samples. The strongest intensity staining was observed in osteoblastic osteosarcoma. Conclusion: KPNA2 is frequently expressed in osteosarcomas, particularly in osteoblastic and chondroblastic tumors, but is rarely positive in chondrosarcomas and ESs. This feature may aid in distinguishing between osteosarcoma and other bone sarcoma mimics. This report supports KPNA2 as a novel marker for the diagnosis of osteosarcoma.