Prognostic significance of cathepsin-D expression in node-positive breast carcinoma: An immunohistochemical study

Authors

  • Bernard Tětu,

    Corresponding author
    1. Department of Pathology and Centre de recherche en cancérologie de ľ Université Laval, Ľ Hǒtel-Dieu de Québec, Canada
    • Department of Pathology, Ľ Hǒtel-Dieu de Québec, 11, cǒte du Palais, Québec, Québec, Canada G1R 2J6. Fax: (418) 691-5226
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  • Chantal Cǒté,

    1. Department of Pathology and Centre de recherche en cancérologie de ľ Université Laval, Ľ Hǒtel-Dieu de Québec, Canada
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  • Sonia Brisson,

    1. Department of Pathology and Centre de recherche en cancérologie de ľ Université Laval, Ľ Hǒtel-Dieu de Québec, Canada
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  • Nancy Roberge,

    1. Department of Pathology and Centre de recherche en cancérologie de ľ Université Laval, Ľ Hǒtel-Dieu de Québec, Canada
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  • Jacques Brisson,

    1. Groupe de recherche en Epidémiologic de ľ Université Laval, Hǒpital du St-Sacrement, Québec, Canada
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  • Diane Potvin

    1. Groupe de recherche en Epidémiologic de ľ Université Laval, Hǒpital du St-Sacrement, Québec, Canada
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Abstract

The prognostic significance of cathepsin-D expression was evaluated by immunohistochemistry in 638 node-positive breast carcinomas diagnosed between 1980 and 1986. A minimum of 2.5 years of follow-up was available for each patient (maximum: 9.5 years). Cathepsin-D expression was assessed separately both in cancer and in stromal cells using a commercially available polyclonal antibody. While cancer-cell immunostaining was not associated with prognosis, positive staining of stromal elements was related to shorter metastasis-free survival. The difference in distant metastasis-free survival between positive and negative expressors was greatest in the sub-group of patients submitted to adjuvant chemotherapy, with a hazard ratio for occurrence of distant metastasis of 1.76 by multivariate analysis, but was lowest for those receiving hormone therapy. Cathepsin-D expression by stromal cells was related to HER-2/ neu oncoprotein expression, HSP-27 expression, poor nuclear grade, aneuploidy, and absence of estrogen and progesterone receptors. No association was found with the number of involved lymph nodes, tumor size, age, histologic grade, S-phase fraction, or vascular invasion. Our study suggests that cathepsin-D expression by stromal cells (and not by cancer cells) affects the prognosis of breast cancer, that stromal cells probably play a key role in local invasion and metastatic dissemination of the tumor, and that the prognostic significance of cathepsin-D expression may vary according to the type of adjuvant therapy.

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