Tissue expression and serum levels of the oncoprotein HER-2/neu in 157 primary breast tumours

Background: We studied HER-2 expression in paired serum and tissue samples, in 157 selected cases from 701 consecutive primary breast cancer patients with pretreatment HER-2 extracellular domain (ECD) >= 10 ng/ml, or < 10 ng/ml but showing a HER-2 ECD lead time before first metastasis. Patients and Methods: HER-2 ECD was measured by the Immuno I automated ELISA (Bayer). Tumour tissue was analysed by immunohistochemistry (IHC) with Dako A 0485 and CB I I antibodies and scored with the Dako scoring system. Results: Mean HER-2 ECD was 12.48 +/- 7.08 nglml and 21/157 (13.4%) sera were >= 15 ng/ml (cut-off). Forty tumours (25.48%) showed both invasive and intraductal components, 3 (1.91 %) were pure in situ carcinomas and 114 (72.61 %) were pure invasive tumours. Elevated HER-2 ECD concentration was related only to pT (p = 0.0008), histological grade (p = 0.0465), presence of comedonecrosis (p = 0.0123) or comedo-type carcinoma (p=0.041) and was unrelated to the presence of an intraductal component. HER-2 ECD was >= 15 nglml in 48% of Dako 3+ and 60% of CB 11 2+ and 3+ tumours. By logistic regression analysis, the significant parameters associated with HER-2 ECD concentration were pT (p = 0. 0038) and Dako 3 + scores (p = 0. 0005). In Dako 3 + or CB 11 2+3+ tumours, elevated mean HER-2 ECD concentrations were observed only when pT exceeded 28-30 mm (p = 0. 0062 and p = 0. 0036, respectively). Conclusion: In breast tumours, a threshold in size and HER-2 overexpression is necessary to observe elevated concentrations of HER-2 ECD at diagnosis. This information may be useful when the primary tumour is not available for IHC.