Differential expression of somatostatin receptors, p44/42 mapk, and mtor activation in medulloblastomas and primitive neuroectodermal tumors

Mahlon Johnson, Mary J. O'Connell, Howard Silberstein, David Korones

Research output: Contribution to journalArticle

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Abstract

Recently, somatostatin receptors (SSR) have been identified on medulloblastomas and proposed as a new target for chemotherapy including inhibitory somatostatin analogs. Activation of SSRs inhibit growth, in part, by activating phosphatases that dephosphorylate/deactivate growth stimulatory signaling of the MEK1-p44/42 MAPK and PI3K-Akt-mTOR pathways. These SSR-inhibited signaling pathways have not been characterized or correlated with SSR expression in medulloblastomas or primitive neuroectodermal tumors (PNETs), yet may represent additional targets for combined chemotherapy. We evaluated the distribution and extent of SSR1 and SSR2 expression and correlated it with activation of downstream MEK1-p44/42 MAPK and PI3K-Akt-mTOR pathways in medulloblastomas and PNETs. Sections from 22 medulloblastomas and 9 PNETs were compared using immunohistochemistry with monoclonal antibodies to SSR1, SSR2, p44/42 MAPK, phosphorylated p44/42 MAPK, and phosphorylated mTOR. SSR1 was detected in 50% of medulloblastomas, extensive in 46%, and similar in classic, desmoplastic, and large cell/anaplastic subtypes. SSR1 was detected in 78% of PNETs and extensive in the majority. SSR2 was found in 18% of medulloblastomas and 33% of PNETs. Activated/ phosphorylated pMAPK 44/42 was detected in 82% of medulloblastomas, all subtypes, and in 62.5% of PNETs with coexpression of SSR1 in one third. Activated/phosphorylated mTOR was found in only 18% of medulloblastomas but in 88% of PNETs. SSR1 coexpression with activated/phosphorylated mTOR was identified in 75% of PNETs. These findings suggest that addition of an mTOR inhibitor may potentiate growth inhibitory effects of SSR agonists in the treatment of PNETs. Immunohistochemical identification of mTOR activation/phosphorylation in biopsies of initial and treatment-resistant PNETs may facilitate development of clinical trials and therapeutic decisions.

Original languageEnglish (US)
Pages (from-to)532-538
Number of pages7
JournalApplied Immunohistochemistry and Molecular Morphology
Volume21
Issue number6
DOIs
StatePublished - Mar 4 2013

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Primitive Neuroectodermal Tumors
Somatostatin Receptors
Medulloblastoma
Mitogen-Activated Protein Kinase 3
Phosphatidylinositol 3-Kinases
Growth
Drug Therapy
Somatostatin
Phosphoric Monoester Hydrolases
Therapeutics
Immunohistochemistry
Monoclonal Antibodies
Phosphorylation
Clinical Trials
Biopsy

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Histology
  • Medical Laboratory Technology

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Differential expression of somatostatin receptors, p44/42 mapk, and mtor activation in medulloblastomas and primitive neuroectodermal tumors. / Johnson, Mahlon; O'Connell, Mary J.; Silberstein, Howard; Korones, David.

In: Applied Immunohistochemistry and Molecular Morphology, Vol. 21, No. 6, 04.03.2013, p. 532-538.

Research output: Contribution to journalArticle

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