Long-term prognostic significance of neoangiogenesis in breast carcinomas: comparison of Tie-2/Tek, CD105, and CD31 immunocytochemical expression

• Published in: Human pathology 2004-02, Vol.35 (2), p.176-183
• Main Authors: Dales, Jean P, Garcia, Stephane, Carpentier, Severine, Andrac, Lucile, Ramuz, Oliver, Lavaut, Marie N, Allasia, Claude, Bonnier, Pascal, Charpin, Colette
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Analysis of Variance; Angiogenesis; Antigens, CD; Biological and medical sciences; Breast cancer; Breast Neoplasms - blood supply; Breast Neoplasms - chemistry; CD105; CD31; Endoglin; Female; Gene amplification; Gene Expression Regulation, Neoplastic; Gynecology. Andrology. Obstetrics; Humans; Immunohistochemistry; Investigative techniques, diagnostic techniques (general aspects); Mammary gland diseases; Medical sciences; Middle Aged; Mortality; Multivariate Analysis; Neovascularization, Pathologic - metabolism; Neovascularization, Pathologic - pathology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Platelet Endothelial Cell Adhesion Molecule-1 - analysis; Predictive Value of Tests; Prognosis; Receptor, TIE-2 - analysis; Receptors, Cell Surface; Rodents; Studies; Surgery; Survival Analysis; Tie-2/Tek; Time Factors; Tumors; Vascular Cell Adhesion Molecule-1 - analysis
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2003.10.008

The immunocytochemical detection of Tie-2/Tek, CD105, and CD31 was assessed in a large series (n = 905) of breast carcinomas on frozen sections. Results were correlated with patients’ long-term outcome (median, 11.7 years) to define the respective prognostic significance of these markers. Univariate (Kaplan-Meier) analysis demonstrated that higher expression of CD31 ( P = 0.032), CD105 ( P = 0.001), and Tie-2/Tek ( P = 0.025) correlated with poorer survival. However, only greater CD105 expression could significantly ( P = 0.035) identify node-negative patients with poorer survival. Moreover, in multivariate analysis, CD105 and Tie-2/Tek, but not CD31, expression proved to be independent significant prognostic indicators. Marked expression of CD31 ( P = 0.024), CD105 ( P = 0.001), and Tie-2/Tek ( P = 0.01) also correlated with higher risk of metastases in node-negative patients. It is concluded that CD105 immunoexpression in breast carcinomas is an independent prognostic indicator in node-negative patients, better in terms of overall survival than Tie-2/Tek and CD31. Also, Tie-2/Tek expression proved more sensitive than CD31 expression in terms of prognostic significance. Compared with CD31, CD105 and Tie-2/Tek have more clinical relevance for patient monitoring and also can serve as targets for specific therapy, such as CD105 immunotoxins or Tie-2/Tek pathway blockade, as recently suggested in experimental studies.