Department of Pathology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, 510630, Guangdong, China.
Department of Pathophysiology, School of Medicine, Jinan University, Guangzhou, 510632, Guangdong, China.
Diagn Pathol. 2020 Nov 11;15(1):135. doi: 10.1186/s13000-020-01051-6.
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).
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.
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.
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.
亲核蛋白α2（KPNA2）是亲核蛋白α 家族的成员，已在多种癌症中进行了研究，但在恶性骨肿瘤中尚未得到充分研究。本研究的目的是评估 KPNA2 蛋白的表达水平，并将其作为骨肉瘤和恶性骨肿瘤模拟物（如软骨肉瘤和尤文肉瘤（ES））的新型诊断生物标志物进行研究。
我们通过免疫组织化学法检测了 223 例恶性和良性骨肿瘤石蜡包埋手术标本中 KPNA2 蛋白的表达，包括 81 例骨肉瘤、42 例软骨肉瘤、15 例 ES、28 例骨样骨瘤、20 例骨软骨瘤和 37 例软骨母细胞瘤。根据染色范围和强度进行半定量评分。
81 例骨肉瘤中有 67 例（82.7%）、42 例软骨肉瘤中有 0 例（0%）和 15 例 ES 中有 1 例（6.7%）显示 KPNA2 免疫反应性。所有良性骨肿瘤均未见 KPNA2 表达阴性。骨肉瘤样本中 KPNA2 的表达明显高于软骨肉瘤和 ES 样本（P<0.001）。KPNA2 免疫表达检测骨肉瘤的灵敏度和特异性分别为 82.7%和 100%。分析了几种骨肉瘤亚型，发现 KPNA2 在成骨细胞样本中免疫染色频繁（90.9%），其中 39 例（70.9%）表现为强染色强度。在 13 例软骨母细胞瘤中有 10 例（76.9%）、6 例纤维母细胞瘤中有 2 例（33.3%）、4 例血管扩张型中有 3 例（75.0%）和 3 例巨细胞瘤中有 2 例（66.7%）可见 KPNA2 阳性。最强的染色强度见于成骨细胞骨肉瘤。
KPNA2 在骨肉瘤中经常表达，特别是在成骨细胞和成软骨细胞瘤中，但在软骨肉瘤和 ES 中很少阳性。这一特征可能有助于鉴别骨肉瘤和其他骨肉瘤模拟物。本报告支持 KPNA2 作为骨肉瘤诊断的新型标志物。
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