Finansiering av laboratoriekostnader
Overexpression of c-erbB2 is a negative prognostic factor in anapl. astrocytomas
Prosjektet går ut på å påvise ulike signalmolekyler i vevsnitt fra hjernesvulster og som kan ha diagnostisk, prognostisk og terapeutisk verdi.
Artikkel med denne tittel, forfattere: S Gulati, B Ytterhus, M Gulati, S Lydersen, og SH Torp, ble sendt inn des. 2009 til et internasjonalt krefttidsskrift (J Clin Exp Cancer Res)
The epidermal growth factor receptor (EGFR) family, consisting of four tyrosine kinase receptors, c-erbB1-4, seems to be influential in the tumorigenesis of human gliomas. The aim of this study was to investigate EGFR gene amplification and expression of c-erbB1-4 receptor expression in anaplastic astrocytomas. Formalin-fixed and paraffin-embedded sections from 31 human anaplastic astrocytomas were investigated by standard immunohistochemical procedures for expression of c-erbB1-4 receptor proteins using commercial antibodies. EGFR gene amplification was studied by FISH using paraffin-embedded tissues. Two monoclonal antibodies were used for EGFR detection. NCL-EGFR-384 and NCL-EGFR displayed positive immunoreactivity in 97% and 71%, respectively. For c-erbB2 detection three monoclonal antibodies were applied. The antibody clones CB11, 3B5, and 5A2 displayed positive immunoreactivity in 45%, 100%, and 52%, respectively. C-erbB3 immunoreactivity occurred in 27 out of 31 anaplastic astrocytomas (97%). c-erbB4 immunoreactivity was present in 23 out of 31 cases (74%). The EGFR gene was amplified in 9 out of 31 tumors (29%) by fluorescence in situ hybridization. After adjusting for age, Karnofsky performance status, and extent of surgical resection, Cox multiple regression analysis with overall survival as the dependent variable revealed that c-erbB2 overexpression detected by the monoclonal antibody clone CB11 was a statistically significant poor prognostic factor in patients with anaplastic astrocytoma (P = 0.004). This study shows the convenience and feasibility of immunohistochemistry when determining the expression of receptor proteins in tumor tissue. In this regard, standardization of the procedures is a prerequisite and a challenge. Our findings imply that c-erbB2 overexpression predicts aggressive behaviour in anaplastic astrocytomas. C-erbB2 seems to play an important role in the pathogenesis of anaplastic astrocytomas and may provide a novel target for therapy.