Immunohistochemical analysis of receptor tyrosine kinase signal transduction activity in chordoma
- 31 October 2007
- journal article
- Published by Wiley in Neuropathology and Applied Neurobiology
- Vol. 34 (1), 95-104
- https://doi.org/10.1111/j.1365-2990.2007.00873.x
Abstract
Currently, there are no effective chemotherapeutic protocols for chordoma. Reports of receptor tyrosine kinase (RTK) expression in chordoma suggest that these tumours may respond to kinase inhibitor therapy. However, RTK signalling activity has not been extensively investigated in chordoma. A tissue microarray containing 21 cases of chordoma was analysed for expression of a number of proteins involved in signal transduction from RTKs by immunohistochemistry. Platelet-derived growth factor receptor-beta, epidermal growth factor receptor (EGFR), KIT and HER2 were detected in 100%, 67%, 33% and 0% of cases, respectively. Platelet-derived growth factor receptor-beta staining was of moderate-to-strong intensity in 20 of 21 cases. In contrast, KIT immunoreactivity was weak and focal in each of the seven positive cases. Total EGFR staining was variable; weak staining for phosphorylated EGFR was detected in nine cases. Phosphorylated isoforms of p44/42 mitogen-activated protein kinase, Akt and STAT3, indicative of tyrosine kinase activity, were detected in 86%, 76% and 67% of cases, respectively. Chordomas commonly express RTKs and activated signal transduction molecules. Although there were no statistically significant correlations between the expression of any of the markers studied and disease-free survival or tumour location, the results nonetheless indicate that chordomas may respond to RTK inhibitors or modulators of other downstream signalling molecules.This publication has 36 references indexed in Scilit:
- American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in Breast CancerJournal of Clinical Oncology, 2007
- Effectiveness of Cetuximab/Gefitinib in the Therapy of a Sacral ChordomaOncology Research and Treatment, 2006
- Activating mutations in c-KIT and PDGFRα are exclusively found in gastrointestinal stromal tumors and not in other tumors overexpressing these imatinib mesylate target genesCancer Biology & Therapy, 2005
- Tyrosine kinase receptors as attractive targets of cancer therapyCritical Reviews in Oncology/Hematology, 2004
- The JAK/STAT signaling pathwayJournal of Cell Science, 2004
- Phase I Study of the Humanized Antiepidermal Growth Factor Receptor Monoclonal Antibody EMD72000 in Patients With Advanced Solid Tumors That Express the Epidermal Growth Factor ReceptorJournal of Clinical Oncology, 2004
- Targeted Therapies for Cancer 2004American Journal of Clinical Pathology, 2004
- Phosphorylation State-Specific Antibodies: Applications in Investigative and Diagnostic PathologyThe American Journal of Pathology, 2003
- Expression of Growth Factors and Structural Proteins in Chordomas: Basic Fibroblast Growth Factor, Transforming Growth Factor ??, and Fibronectin Are Correlated with RecurrenceNeurosurgery, 2002
- Chemotherapy for cranial base tumorsJournal of Neuro-Oncology, 1994