PROGNOSTIC VALUE OF CATHEPSIN-D IN BREAST-CANCER - COMPARISON OF IMMUNOHISTOCHEMICAL AND IMMUNORADIOMETRIC DETECTION METHODS

Aim-To test whether immunoradiometric or immunohistochemical detection of lysosomal protease cathepsin D in breast cancer is more predictive of outcome. Methods-Tumour tissues from 270 primary breast cancer pat ients were evaluated for the expression of cathepsin D using immunohis tochemistry (IH; paraffin embedded tissues) and an immunoradiometric a ssay (IRMA; cytosol from frozen tissues). Immunohistochemical scores w ere based on immunoreaction in tumour cells and tumour associated macr ophages. Results-IRMA values (cut off 40 fmol/mg cell protein) correla ted significantly with IH values. Recorded incidences of positive immu noreaction in tumour cells using two different cut off values were 52% and 35%, respectively. Macrophages stained positive in 31% of tissues . Combined evaluation of tumour cells and macrophages resulted in posi tivity rates of 59% and 48%, respectively. Node status was the only va riable found to correlate with cathepsin D expression. IH results corr elated significantly with clinical outcome (median observation time 68 months) in node negative patients (n=120) but not in node positive pa tients (n=145). Cathepsin D positivity as measured by IRMA was not rel ated to clinical outome in either group. On multivariate analysis in t he node negative group, IH detection of cathepsin D appeared to be the only independent factor indicating prognosis. For node positive patie nts, tumour grade, size, and receptor status were of prognostic releva nce. Conclusions-Because of the simple methodology and the minimal amo unt of tissue used for analysis, immunohistochemistry was preferred to immunoradiometry for cathepsin D measurement; it also provided more p redictive data with respect to prognosis.