Krishnan Chandra, Higgins John P, West Robert B, Natkunam Yasodha, Heerema-McKenney Amy, Arber Daniel A
Department of Pathology, Stanford University, Stanford, CA 94205, USA.
Am J Surg Pathol. 2009 Nov;33(11):1695-704. doi: 10.1097/PAS.0b013e3181b0ebdc.
Microtubule-associated protein-2 (MAP-2) is a protein expressed in high levels in cells derived from the neural crest. To the best of our knowledge, MAP-2 expression has not been thoroughly evaluated in tissues outside of the central nervous tissue. We examined the diagnostic utility of MAP-2 as a marker of neuroblastoma and attempted to characterize the expression of this protein in other tumors in the morphologic differential diagnosis of neuroblastoma.
MAP-2 showed significant cytoplasmic reactivity in 95% of primary and 100% of metastatic neuroblastomas. Included within this set of tumors were 3 undifferentiated neuroblastomas, all of which showed strong staining. MAP-2 did not show significant staining in the majority of other small round blue cell tumors within the morphologic differential. Additionally, MAP-2 showed comparable sensitivity in staining primary neuroblastomas as compared with synaptophysin, chromogranin, CD56, and beta-catenin. In contrast to other markers of neuroblastoma, MAP-2 did not show significant cross reactivity to native bone marrow precursors, thus eliminating a potential source of confusion. In normal tissues, MAP-2 staining was essentially restricted to organs derived from the neural crest (adrenal medulla, endocrine organs). Variant patterns of staining were seen in exocrine organs, monocyte/macrophages and solitary fibrous tumor/hemangiopericytoma family of tumors. Rarely, high-grade adult sarcomas exhibiting strong cytoplasmic MAP-2 staining were seen.
MAP-2 is a sensitive and specific marker of neuroblastoma, both in the primary tumor and bone marrow biopsy settings. We think that MAP-2, in conjunction with synaptophysin, is a very powerful immunohistochemical marker in differentiating neuroblastoma from its morphologic mimics.
微管相关蛋白2（MAP-2）是一种在神经嵴来源的细胞中高表达的蛋白质。据我们所知，MAP-2在中枢神经组织以外的组织中尚未得到充分评估。我们研究了MAP-2作为神经母细胞瘤标志物的诊断效用，并试图在神经母细胞瘤的形态学鉴别诊断中描述该蛋白在其他肿瘤中的表达情况。
MAP-2在95%的原发性神经母细胞瘤和100%的转移性神经母细胞瘤中显示出显著的细胞质反应性。这组肿瘤中包括3例未分化神经母细胞瘤，均显示强染色。在形态学鉴别诊断中的大多数其他小圆形蓝细胞肿瘤中，MAP-2未显示出显著染色。此外，与突触素、嗜铬粒蛋白、CD56和β-连环蛋白相比，MAP-2在原发性神经母细胞瘤染色中显示出相当的敏感性。与神经母细胞瘤的其他标志物不同，MAP-2对天然骨髓前体细胞未显示出显著交叉反应性，从而消除了潜在的混淆来源。在正常组织中，MAP-2染色基本局限于神经嵴来源的器官（肾上腺髓质、内分泌器官）。在外分泌器官、单核细胞/巨噬细胞以及孤立性纤维瘤/血管外皮细胞瘤家族性肿瘤中可见不同的染色模式。很少见到高级别成人肉瘤呈现强细胞质MAP-2染色。
MAP-2是神经母细胞瘤原发肿瘤和骨髓活检中的一种敏感且特异的标志物。我们认为，MAP-2与突触素联合使用，在鉴别神经母细胞瘤与其形态学相似肿瘤方面是一种非常强大的免疫组化标志物。
