Comparison of cathepsin D in breast carcinoma by cytosol immunoassay and immunohistochemistry

Abstract

Cathepsin D (CATD) is an oestrogen regulated lysosomal protease which has been shown by cytosol immunoassay to be an independent predictor of prognosis and survival in breast carcinoma. It is now possible to also determine the presence of CATD by immunohistochemistry (IHC) using commercially available antisera. This study compared the IHC method of CATD measurement with cytosol immunoassay (RIA). We measured CATD levels in 61 breast carcinoma specimens. The IHC was performed on conventional formalin fixed paraffin embedded tissue with a commercially available antibody (Novocastra, Newcastle-upon-Tyne) and the RIA with a commercially available method (CIS ELSA-CathD immunoradiometric assay, Intemation CIS, Gif-sur-Yverre, France). The extent of immunohistochemical tumour staining of CATD was significantly correlated with RIA estimates (Spearman correlation=0.423, p<0.005). For a given level of IHC staining there was a wide variation in RIA CATD levels. Some tumours contained abundant macrophages which showed considerable IHC staining. The macrophage CATD staining in a specimen was relatively constant while tumour cells showed heterogeneity. Six tumours (10%) with high RIA estimates had a major contribution of CATD from abundant macrophage staining. The prognostic significance of this is unknown at present. There is a strong correlation between the RIA and IHC methods of measuring CATD. However there is a wide variation in results which may be contributed to by tumour and sample heterogeneity and lack of precision in IHC determination. The significance of macrophage staining is also unknown. Further longitudinal survival studies using these techniques are needed to determine which is the more clinically useful.