IMMUNOHISTOCHEMICAL DETECTION OF THERAPEUTIC TARGETS IN MALIGNANT PEDIATRIC BRAIN TUMORS

Publication Type:

Journal Article

Source:

Neuro-Oncology, Volume 16, p.145-145 (2014)

URL:

http://scholars.fhcrc.org/4598/

Keywords:

2014, August 2014, Clinical Research Division, Oncology Clinical Neurology Clinical Research Division August 2014 2014Q3

Abstract:

Specific protein detection by immunohistochemistry may predict patient survival and identify opportunities for targeted therapy in a variety of malignancies. We studied a single institution cohort of pediatric patients who underwent neurosurgical resection of malignant brain tumors at Seattle Children’s Hospital between 2000-2011. EGFR, ERBB2, pS6, CD117, pERK, and PDGFRa status was evaluated in tissue microarrays by immunohistochemical staining. Clinical data were obtained from the electronic medical record. The association between clinical factors, protein status and patient survival was analyzed using the Kaplan-Meier method, log-rank test and multivariable Cox regression. Sixty one patients with samples obtained at diagnosis were studied, including medulloblastoma (n = 28), ependymoma (n = 17), supratentorial primitive neuroectodermal tumor (n = 6) and high grade glioma (n = 10); 13 patients also had paired specimens obtained at relapse. Median age at diagnosis was 7.9 years (range 0.2-20) and 61% were male. Five year survival was 70%. The majority (92%) of tumors obtained at diagnosis and 100% of tumors at relapse were positive for at least one of the six proteins studied. EGFR, PDGFRa and pS6 positivity at diagnosis were each associated with death, and were found in 16% (10/61), 73% (44/60) and 54% (33/61) of tumors, respectively. Five-year survival was 18% for subjects with EGFR positive tumors, compared to 80% for subjects with EGFR negative tumors (p < 0.001); 61% and 100% for PDGFRa positive and negative tumors (p = 0.03); and 56% and 88% for pS6 positive and negative tumors (p = 0.02). When adjusted for tumor histology, positive EGFR status at diagnosis remained predictive of death (p = 0.005). EGFR, PDGFRa and pS6 positivity were associated with death in malignant pediatric brain tumors. Further evaluation of mechanisms to target these pathways in brain tumors is warranted.

Notes:

ISI Document Delivery No.: AJ8AK Times Cited: 0 Cited Reference Count: 0 Cole, Bonnie Rudzinski, Erin Anderson, Maya Bloom, Karina Lee, Amy Leary, Sarah 16th International Symposium on Pediatric Neuro-Oncology (ISPNO) JUN 28-JUL 02, 2014 Singapore, SINGAPORE OXFORD UNIV PRESS INC CARY NEURO-ONCOLOGY 1