Microtubule-associated Protein-2 is a Sensitive Marker of Primary and Metastatic Neuroblastoma

Krishnan, Chandra; Higgins, Julian P T; West, Robert B.; Natkunam, Yasodha; Heerema-McKenney, Amy; Arber, Daniel A.

doi:10.1097/pas.0b013e3181b0ebdc

Cited by 18 publications

(13 citation statements)

References 16 publications

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“…MAP-2, a marker of neural crest derivatives, has been reported in multiple neoplasms including paragangliomas and neuroblastoma. 18,22,40 Although another study has examined MAP-2 reactivity in pheochromocytoma with immunoreactivity in 13 of 18 (72%) cases, none to our knowledge have formally investigated immunoreactivity in adrenal cortical lesions. MAP-2 showed positive immunoreactivity in 89% of pheochromocytomas using a Z2+ staining intensity prerequisite.…”

Section: Discussionmentioning

confidence: 93%

A Tissue Microarray-based Comparative Analysis of Novel and Traditional Immunohistochemical Markers in the Distinction Between Adrenal Cortical Lesions and Pheochromocytoma

Sangoi¹,

McKenney

2010

American Journal of Surgical Pathology

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We have encountered an increasing number of image-guided adrenal mass biopsies in which the differential diagnosis is adrenal cortical lesion versus pheochromocytoma. This distinction is sometimes difficult because of confounding clinical presentations, overlapping morphologies, and some degree of immunophenotypic overlap including focal staining with markers of purported lineage specificity. Interventional radiologists commonly use narrow gauge biopsy needles in this setting, which yield scant diagnostic tissue and further complicate pathologic evaluation. In this study, a detailed immunoprofile of 63 adrenal cortical lesions (3 adrenal rests, 6 adrenal cortical hyperplasias, 43 adrenal cortical adenomas, 4 adrenal cortical neoplasms of uncertain malignant potential, and 7 adrenal cortical carcinomas) was compared with 35 pheochromocytomas using traditional (calretinin, chromogranin, inhibin, melanA, and synaptophysin) and novel [steroidogenic factor-1 (SF-1), microtubule-associated protein 2, and mammalian achaete-scute homolog-1] antibodies, using tissue microarray technology to simulate small image-guided biopsies. Staining extent and intensity were each scored semiquantitatively for each antibody. A comparison of sensitivity and specificity using different intensity thresholds required for a "positive" result (> or = 1+ vs. > or = 2+) was performed. Staining results based on a > or = 1+ and (> or = 2+) intensity threshold were as follows: calretinin-95% (89%) in adrenal cortical lesions and 14% (0%) in pheochromocytomas; chromogranin-0% in adrenal cortical lesions and 100% in pheochromocytomas; inhibin-97% (86%) in adrenal cortical lesions and 6% (0%) in pheochromocytomas; microtubule-associated protein 2-29% (16%) in adrenal cortical lesions and 100% (89%) in pheochromocytomas; mammalian achaete-scute homolog-1-0% in both adrenal cortical lesions and pheochromocytomas; melanA-94% (86%) in adrenal cortical lesions and 6% (0%) in pheochromocytomas; SF-1-87% (86%) in adrenal cortical lesions and 0% in pheochromocytomas; synaptophysin-67% (59%) in adrenal cortical lesions and 100% in pheochromocytomas. Using an antibody panel consisting of chromogranin plus the nuclear antibody SF-1 and either calretinin or inhibin, while requiring a high-staining intensity threshold, helps to eliminate interpretative issues of artifactual or background reactivity, improves diagnostic sensitivity/specificity, and makes for an effective immunohistochemical approach in distinguishing adrenal cortical lesions from pheochromocytomas.

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Section: Discussionmentioning

confidence: 93%

A Tissue Microarray-based Comparative Analysis of Novel and Traditional Immunohistochemical Markers in the Distinction Between Adrenal Cortical Lesions and Pheochromocytoma

Sangoi¹,

McKenney

2010

American Journal of Surgical Pathology

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“…These included proteins regulating proliferation (β-catenin/FZD1, SHH/Gli1/PTCH1, TrkB/BDNF, PDGFR), apoptosis (FZD1, Gli1), chemo-resistance (FZD1, Telomerase), angiogenesis (VEGF/VEGFR, PDGFRβ, SHH), metastasis (SHH, MAP2, TrkB), adhesion and migration (NCAM, TrkB, Dcx), and differentiation and neurite extension (MAP2, Dcx) (Eggert et al, 2000; Oltra et al, 2005; Nakamura et al, 2006; Flahaut et al, 2009; Korja et al, 2009; Krishnan et al, 2009; Bahnassy et al, 2010; Oue et al, 2010; Souzaki et al, 2010; Wesbuer et al, 2010; Zhang et al, 2010; Schiapparelli et al, 2011). Western blot analysis revealed differences in expression of PDGFRβ, MAP2, Dcx, NCAM, survivin, and β-catenin (Figures 6A,B), thereby identifying these molecules as potential unique markers of AI or AD phenotypes.…”

Section: Resultsmentioning

confidence: 99%

Reversible adaptive plasticity: a mechanism for neuroblastoma cell heterogeneity and chemo-resistance

Chakrabarti¹

2012

Front. Oncol.

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We describe a novel form of tumor cell plasticity characterized by reversible adaptive plasticity in murine and human neuroblastoma. Two cellular phenotypes were defined by their ability to exhibit adhered, anchorage dependent (AD) or sphere forming, anchorage independent (AI) growth. The tumor cells could transition back and forth between the two phenotypes and the transition was dependent on the culture conditions. Both cell phenotypes exhibited stem-like features such as expression of nestin, self-renewal capacity, and mesenchymal differentiation potential. The AI tumorspheres were found to be more resistant to chemotherapy and proliferated slower in vitro compared to the AD cells. Identification of specific molecular markers like MAP2, β-catenin, and PDGFRβ enabled us to characterize and observe both phenotypes in established mouse tumors. Irrespective of the phenotype originally implanted in mice, tumors grown in vivo show phenotypic heterogeneity in molecular marker signatures and are indistinguishable in growth or histologic appearance. Similar molecular marker heterogeneity was demonstrated in primary human tumor specimens. Chemotherapy or growth factor receptor inhibition slowed tumor growth in mice and promoted initial loss of AD or AI heterogeneity, respectively. Simultaneous targeting of both phenotypes led to further tumor growth delay with emergence of new unique phenotypes. Our results demonstrate that neuroblastoma cells are plastic, dynamic, and may optimize their ability to survive by changing their phenotype. Phenotypic switching appears to be an adaptive mechanism to unfavorable selection pressure and could explain the phenotypic and functional heterogeneity of neuroblastoma.

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“…It was found to be increased during prostate cancer progression to metastasis in an expression profiling approach and its over‐expression resulted in chromosomal ploidy. Six other antigens (RPIA, NOVA2, MAP2, HSPH1, RASSF7, and RBM15) have been linked to other forms of cancers (Table II) 29–38. Interestingly, high titers of serum autoantibodies against NOVA proteins (also called anti‐Ri antibodies) were detected in patients with ospoclonus myoclonus syndrome, a rare neurological disorder associated with latent cancer 30, 39, 40.…”

Section: Resultsmentioning

confidence: 99%

Serum‐autoantibodies for discovery of prostate cancer specific biomarkers

et al. 2011

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Microtubule-associated Protein-2 is a Sensitive Marker of Primary and Metastatic Neuroblastoma

Abstract: 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.

Cited by 18 publications

References 16 publications

A Tissue Microarray-based Comparative Analysis of Novel and Traditional Immunohistochemical Markers in the Distinction Between Adrenal Cortical Lesions and Pheochromocytoma

A Tissue Microarray-based Comparative Analysis of Novel and Traditional Immunohistochemical Markers in the Distinction Between Adrenal Cortical Lesions and Pheochromocytoma

Reversible adaptive plasticity: a mechanism for neuroblastoma cell heterogeneity and chemo-resistance

Serum‐autoantibodies for discovery of prostate cancer specific biomarkers

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