The Prognostic Value of Cathepsin D in Breast Cancer. A Long Road to the Clinic

THIS ISSUE of the European Journal of Cancer contains a review on cathepsin D in breast cancer [l] by two basic scientists (pp. 1%24)and an original paper written by physicians and asking a practical question: “What to add to the number of metastatic nodes to select high risk early breast cancer patients?” [2] (pp. 4 l-46). These two papers clearly illustrate the huge distance between an unchanged clinical practice and the explosion of new information provided by basic research. The issue of prognostic biological parameters is exemplary in this respect. The review by Westley and May on the biology of cathepsin D in cancer [l] is well documented and objective and there is little to add except two recent findings. We have recently proposed that cathepsin D overexpression might stimulate cell proliferation of micrometastasis in nude mice by inactivating a secreted growth inhibitor [3] rather than by facilitating evasion through basement membrane. Moreover, the double knock out of the cathepsin D gene in mice [4] has recently indicated that, contrary to other proteases, which are often redundant in their function, cathepsin D is unique at weaning in preventing apoptosis in thymus and epithelial cell renewal in the small intestine. The homozygous new born mice, which develop normally in utero, die at day 25 with small intestine necrosis and thymocyte apoptosis. By contrast, the half-life of bulk proteins was unaltered. One major function of cathepsin D may therefore be to provide essential growth factors for renewal of certain epithelial tissues and to facilitate interactions between epithelial cells and components of extracellular matrix [5] rather than to degrade proteins in lysosomes where other cathepsins can replace cathepsin D. Concerning the clinical significance of cathepsin D, the merit of the review by Westley and May is to integrate the different clinical studies performed independently from 1989 to date and to draw tentative conclusions on the prognostic value of cathepsin D. The overall bad prognostic significance