Microtubule-associated protein-2 is a sensitive marker of primary and metastatic neuroblastoma

Am J Surg Pathol. 2009 Nov;33(11):1695-704. doi: 10.1097/PAS.0b013e3181b0ebdc.

Abstract

Background: 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.

Results: 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.

Conclusions: 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.

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Bone Marrow Neoplasms / diagnosis
  • Bone Marrow Neoplasms / metabolism
  • Bone Marrow Neoplasms / secondary
  • Cytoplasm / metabolism
  • Cytoplasm / pathology
  • Diagnosis, Differential
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Microtubule-Associated Proteins / metabolism*
  • Neuroblastoma / diagnosis*
  • Neuroblastoma / metabolism
  • Neuroblastoma / secondary
  • Predictive Value of Tests
  • Synaptophysin / metabolism
  • Tissue Array Analysis

Substances

  • Biomarkers, Tumor
  • MAP2 protein, human
  • Microtubule-Associated Proteins
  • Synaptophysin