Cathepsin D expression detected by immunohistochemistry has independent prognostic value in axillary node-negative breast cancer. 1993

J Isola, and S Weitz, and T Visakorpi, and K Holli, and R Shea, and N Khabbaz, and O P Kallioniemi
Department of Biomedical Sciences, University of Tampere, Finland.

OBJECTIVE Increased expression of the lysosomal protease cathepsin D (CD) has been implicated in the metastatic progression of breast cancer. This study was designed to determine the prognostic significance of CD expression in axillary node-negative (ANN) breast cancer. The relationship of CD expression and onset of soft tissue recurrences and visceral metastatases was also studied. METHODS We analyzed a population-based group of 262 ANN breast cancer patients, none of whom had received any adjuvant chemotherapy or endocrine therapy. An immunohistochemical method based on a new monoclonal antibody (1C11) with a distinct epitope specificity made it possible to study CD expression from archival paraffin-embedded specimens and to distinguish staining in tumor cells from the high-level expression found in tumor-infiltrating macrophages. RESULTS High-level CD expression, as defined by cytoplasmic immunoreactivity in greater than 10% of the cancer cells, was found in 95 cases (36%). High-level CD expression was associated with large primary tumor size (P = .014), but not with histologic grade, estrogen and progesterone receptors, DNA index, or S-phase fraction, or with c-erbB-2 and p53 overexpression. Patients with CD-positive tumors developed significantly more often both soft tissue recurrences and visceral metastases (P = .0007) and had a significantly shorter disease-free survival (P < .0001). Eight-year overall survival of patients with high-level CD expression was 64% as compared with 90% in those with low-level expression (relative risk, 2.97; 95% confidence interval [Cl], 1.6 to 4.4; P < .0001). According to a Cox multivariate model and a regression-tree analysis, high-level CD expression was an independent predictor of poor overall survival in conjunction with tumor size and S-phase fraction. CONCLUSIONS These results indicate that CD expression determined by immunohistochemistry is a powerful prognostic factor in ANN breast cancer. The most significant prognostic information was obtained when CD expression (predicting metastatic activity) was combined with estimate of cell-proliferation rate (S-phase fraction).

UI MeSH Term Description Entries
D007124 Immunoenzyme Techniques Immunologic techniques based on the use of: (1) enzyme-antibody conjugates; (2) enzyme-antigen conjugates; (3) antienzyme antibody followed by its homologous enzyme; or (4) enzyme-antienzyme complexes. These are used histologically for visualizing or labeling tissue specimens. Antibody Enzyme Technique, Unlabeled,Enzyme Immunoassay,Enzyme-Labeled Antibody Technique,Immunoassay, Enzyme,Immunoperoxidase Techniques,Peroxidase-Antiperoxidase Complex Technique,Peroxidase-Labeled Antibody Technique,Antibody Enzyme Technic, Unlabeled,Enzyme-Labeled Antibody Technic,Immunoenzyme Technics,Immunoperoxidase Technics,Peroxidase-Antiperoxidase Complex Technic,Peroxidase-Labeled Antibody Technic,Antibody Technic, Enzyme-Labeled,Antibody Technic, Peroxidase-Labeled,Antibody Technics, Enzyme-Labeled,Antibody Technics, Peroxidase-Labeled,Antibody Technique, Enzyme-Labeled,Antibody Technique, Peroxidase-Labeled,Antibody Techniques, Enzyme-Labeled,Antibody Techniques, Peroxidase-Labeled,Enzyme Immunoassays,Enzyme Labeled Antibody Technic,Enzyme Labeled Antibody Technique,Enzyme-Labeled Antibody Technics,Enzyme-Labeled Antibody Techniques,Immunoassays, Enzyme,Immunoenzyme Technic,Immunoenzyme Technique,Immunoperoxidase Technic,Immunoperoxidase Technique,Peroxidase Antiperoxidase Complex Technic,Peroxidase Antiperoxidase Complex Technique,Peroxidase Labeled Antibody Technic,Peroxidase Labeled Antibody Technique,Peroxidase-Antiperoxidase Complex Technics,Peroxidase-Antiperoxidase Complex Techniques,Peroxidase-Labeled Antibody Technics,Peroxidase-Labeled Antibody Techniques,Technic, Enzyme-Labeled Antibody,Technic, Immunoenzyme,Technic, Immunoperoxidase,Technic, Peroxidase-Antiperoxidase Complex,Technic, Peroxidase-Labeled Antibody,Technics, Enzyme-Labeled Antibody,Technics, Immunoenzyme,Technics, Immunoperoxidase,Technics, Peroxidase-Antiperoxidase Complex,Technics, Peroxidase-Labeled Antibody,Technique, Enzyme-Labeled Antibody,Technique, Immunoenzyme,Technique, Immunoperoxidase,Technique, Peroxidase-Antiperoxidase Complex,Technique, Peroxidase-Labeled Antibody,Techniques, Enzyme-Labeled Antibody,Techniques, Immunoenzyme,Techniques, Immunoperoxidase,Techniques, Peroxidase-Antiperoxidase Complex,Techniques, Peroxidase-Labeled Antibody
D008207 Lymphatic Metastasis Transfer of a neoplasm from its primary site to lymph nodes or to distant parts of the body by way of the lymphatic system. Lymph Node Metastasis,Lymph Node Metastases,Lymphatic Metastases,Metastasis, Lymph Node
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D011379 Prognosis A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations. Prognostic Factor,Prognostic Factors,Factor, Prognostic,Factors, Prognostic,Prognoses
D011518 Proto-Oncogene Proteins Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity. Cellular Proto-Oncogene Proteins,c-onc Proteins,Proto Oncogene Proteins, Cellular,Proto-Oncogene Products, Cellular,Cellular Proto Oncogene Proteins,Cellular Proto-Oncogene Products,Proto Oncogene Products, Cellular,Proto Oncogene Proteins,Proto-Oncogene Proteins, Cellular,c onc Proteins
D012044 Regression Analysis Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see LINEAR MODELS) the relationship is constrained to be a straight line and LEAST-SQUARES ANALYSIS is used to determine the best fit. In logistic regression (see LOGISTIC MODELS) the dependent variable is qualitative rather than continuously variable and LIKELIHOOD FUNCTIONS are used to find the best relationship. In multiple regression, the dependent variable is considered to depend on more than a single independent variable. Regression Diagnostics,Statistical Regression,Analysis, Regression,Analyses, Regression,Diagnostics, Regression,Regression Analyses,Regression, Statistical,Regressions, Statistical,Statistical Regressions
D001943 Breast Neoplasms Tumors or cancer of the human BREAST. Breast Cancer,Breast Tumors,Cancer of Breast,Breast Carcinoma,Cancer of the Breast,Human Mammary Carcinoma,Malignant Neoplasm of Breast,Malignant Tumor of Breast,Mammary Cancer,Mammary Carcinoma, Human,Mammary Neoplasm, Human,Mammary Neoplasms, Human,Neoplasms, Breast,Tumors, Breast,Breast Carcinomas,Breast Malignant Neoplasm,Breast Malignant Neoplasms,Breast Malignant Tumor,Breast Malignant Tumors,Breast Neoplasm,Breast Tumor,Cancer, Breast,Cancer, Mammary,Cancers, Mammary,Carcinoma, Breast,Carcinoma, Human Mammary,Carcinomas, Breast,Carcinomas, Human Mammary,Human Mammary Carcinomas,Human Mammary Neoplasm,Human Mammary Neoplasms,Mammary Cancers,Mammary Carcinomas, Human,Neoplasm, Breast,Neoplasm, Human Mammary,Neoplasms, Human Mammary,Tumor, Breast
D002402 Cathepsin D An intracellular proteinase found in a variety of tissue. It has specificity similar to but narrower than that of pepsin A. The enzyme is involved in catabolism of cartilage and connective tissue. EC 3.4.23.5. (Formerly EC 3.4.4.23).
D004273 DNA, Neoplasm DNA present in neoplastic tissue. Neoplasm DNA
D005260 Female Females

Related Publications

J Isola, and S Weitz, and T Visakorpi, and K Holli, and R Shea, and N Khabbaz, and O P Kallioniemi
January 1996, Anticancer research,
J Isola, and S Weitz, and T Visakorpi, and K Holli, and R Shea, and N Khabbaz, and O P Kallioniemi
January 1995, Anticancer research,
J Isola, and S Weitz, and T Visakorpi, and K Holli, and R Shea, and N Khabbaz, and O P Kallioniemi
January 1992, Cancer treatment and research,
J Isola, and S Weitz, and T Visakorpi, and K Holli, and R Shea, and N Khabbaz, and O P Kallioniemi
June 1993, The Tokai journal of experimental and clinical medicine,
J Isola, and S Weitz, and T Visakorpi, and K Holli, and R Shea, and N Khabbaz, and O P Kallioniemi
December 1999, British journal of cancer,
J Isola, and S Weitz, and T Visakorpi, and K Holli, and R Shea, and N Khabbaz, and O P Kallioniemi
January 1999, British journal of cancer,
J Isola, and S Weitz, and T Visakorpi, and K Holli, and R Shea, and N Khabbaz, and O P Kallioniemi
March 1994, Journal of clinical oncology : official journal of the American Society of Clinical Oncology,
J Isola, and S Weitz, and T Visakorpi, and K Holli, and R Shea, and N Khabbaz, and O P Kallioniemi
August 2011, BMC cancer,
J Isola, and S Weitz, and T Visakorpi, and K Holli, and R Shea, and N Khabbaz, and O P Kallioniemi
April 1995, Gan to kagaku ryoho. Cancer & chemotherapy,
J Isola, and S Weitz, and T Visakorpi, and K Holli, and R Shea, and N Khabbaz, and O P Kallioniemi
November 1995, The Journal of pathology,
Copied contents to your clipboard!