Tyrosine kinase receptor expression in chordomas: phosphorylated AKT correlates inversely with outcome

Author(s)

de Castro, Carolina Vieira ^[1] ; Guimaraes, Gustavo ^[2] ; Aguiar, Jr., Samuel ^[2] ; Lopes, Ademar ^[2] ; Baiocchi, Glauco ^[2] ; da Cunha, Isabela Werneck ^[1] ; Froes Marques Campos, Antonio Hugo Jose ^[1] ; Soares, Fernando Augusto ^[1] ; Begnami, Maria Dirlei ^[1]

Affiliation

^[1] Hosp AC Camargo Fund Antonio Prudente, Dept Pathol, BR-01509900 Sao Paulo - Brazil

^[2] Hosp AC Camargo Fund Antonio Prudente, Dept Pelv Surg, BR-01509 Sao Paulo - Brazil

• Document type: Journal article
• Source: HUMAN PATHOLOGY; v. 44, n. 9, p. 1747-1755, SEP 2013.
• Web of Science Citations: 19

Abstract

Chordomas are rare neoplasms arising from notochord remnants. Tyrosine kinase receptors (RTK) are altered in these lesions. We used a tissue microarray containing 58 chordomas to examine the expression of platelet-derived growth factor receptor (PDGFR)-alpha and PDGFR-beta, epidermal growth factor receptor (EGFR), c-Met, c-Kit, pAKT, mammalian target of rapamycin, and HER2 by immunohistochemistry and fluorescence in situ hybridization. Most tumors were positive for PDGFR-alpha (92%), PDGFR-beta (85%), c-Kit (77.4%), c-Met (96%), pAKT (82%), mammalian target of rapamycin (56%), HER2 (24%), and EGFR (26%) by immunohistochemistry. Amplifications or deletions could not be identified for HER2 or EGFR in the 13 cases available for fluorescence in situ hybridization analysis; however, chromosome 7 polysomy was detected in 29% of the cases. The only factor directly associated with a poorer survival rate was pAKT positivity (P = .042). The 5-year survival rate for patients with pAKT-negative chordomas was 100%, whereas it was 45% for patients with pAKT-positive chordomas. Our results confirm that RTKs are frequently altered in chordomas. Given the implications of pAKT positivity, RTK inhibitors might be efficacious, and drugs that inhibit AKT, alone or in combination with radiotherapy, could be an effective treatment for patients with refractory chordomas. (C) 2013 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 09/10458-9 - Thyrosin Kinase receptors in Chordomas
• Grantee: Maria Dirlei Ferreira de Souza Begnami
• Support Opportunities: Regular Research Grants