Abstract P6-01-09: HER4 Is Downregulated in Lymphnode Metastases Compared to the Paired Primary Breast Carcinoma

Abstract

Abstract Introduction: The Human Epidermal Growth Factor Receptor 4 (HER4) of the EGF receptor family has been characterized in both normal and malignant human breast tissue and HER4 overexpression has been shown to predict prolonged survival compared to HER4 receptor negative disease. In our study we investigated the HER4 expression in normal breast tissue, primary breast carcinoma and in ipsilateral metastatic axillary lymphnodes at the time of primary breast cancer surgery. Material and methods: Paired tissue samples from normal breast tissue and primary breast carcinomas were obtained from 169 patients. Out of these a third sample was obtained from 66 patients with metastatic lymphnodes. The primary tumour specimens were sampled uniformly at random. The mRNA expression of HER4 was quantified with real time RT-PCR and expressed relative to the householdgene (HMBS) in arbitrary units (arb.u.). Results: The mRNA expression of HER4 was significantly higher in breast carcinoma with a mean of 2.26 arb.u. [95% c.i.:1.87 to 2.65 arb.u.] than in the paired sample of normal breast tissue with a mean of 0.82 arb.u. [95% c.i.: 0.47 to 1.16 arb.u.] (p=0.0001). The mRNA expression of HER4 was also significantly higher in breast carcinoma than in the corresponding lymphnode mean 0.75 arb. u. [95% c.i.: 0.43 to 1.07 arb.u.] (p=0.015). There was no significant difference observed in mRNA expression of HER4 between the metastatic lymphnode and the corresponding normal breast tissue (P>0.05). When HER4 expression was compared between the primary tumours that had metastasised and those that had not, there was no significant difference (P>0.05). Conclusion: The HER4 expression was high in the primary tumour as compared to normal breast tissue and the corresponding lymphnode. In view of previously published relations between a low expression of HER4 and a poor prognosis our results warrant further studies in order to evaluate whether suppression of HER4 in tumour cells could be involved in lymphogenic metastatic spread. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-01-09.