Expression of the HERI-4 family of receptor tyrosine kinases in breast cancer

Witton, C.J., Reeves, J.R., Going, J.J., Cooke, T.G. and Bartlett, J.M.S. (2003) Expression of the HERI-4 family of receptor tyrosine kinases in breast cancer. Journal of Pathology, 200(3), pp. 290-297. (doi: 10.1002/path.1370)

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EGFr/HER1 and c-erbB-2/HER2 expression are associated with poor prognosis in breast cancer. The type I receptor tyrosine kinase (RTK) family to which they belong has four members (HER1-4). In this study, expression of HER1-4 and oestrogen receptor (ER) expression were determined by inmumohistochemistry in 220 breast carcinomas. Elevated expression of HER1 was observed in 16.4%, HER2 in 22.8%, HER3 in 17.5%, and HER4 in 11.9% of these tumours. Patients whose tumours overexpressed HER1, 2 or 3 had reduced survival (p =less than 0.001), whereas those whose tumours overexpressed HER4 had increased survival (p = 0.013); 38.6% of cases overexpressed one or more of HER1, 2 or 3. HER4 was rarely overexpressed with other HERs (1.4% of cases). Cox's multiple regression analysis demonstrated that overexpression of HER1/2/3, HER4, and standard prognostic indicators independently affected survival. HER1-3 expression was related to ER negativity (P less than 0.0001, chi(2)). Patients with ER- positive, HER1-3-positive tumours had a significantly poorer survival (p less than 0.001) than those with ER-positive/HER-negative or HER4-positive tumours. Expression of HER RTKs displays complex interactions between different family members. There is a strong interaction, in terms of survival, between HER expression and ER expression. The development of HER-targeted agents (eg Herceptin, Iressa), and agents targeted at the downstream signalling pathways, therefore provides new possibilities in the treatment of breast cancer.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Going, Dr James and Cooke, Prof Timothy
Authors: Witton, C.J., Reeves, J.R., Going, J.J., Cooke, T.G., and Bartlett, J.M.S.
Subjects:R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Journal of Pathology

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