Long-term prognostic significance of neoangiogenesis in breast carcinomas: comparison of Tie-2/Tek, CD105, and CD31 immunocytochemical expression.
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.
Department of Pathology, Centre Hospitalier et Universitaire Nord, Marseille, France.
Jean P
JP
Dales
Stephane
S
Garcia
Severine
S
Carpentier
Lucile
L
Andrac
Oliver
O
Ramuz
Marie N
MN
Lavaut
Claude
C
Allasia
Pascal
P
Bonnier
Colette
C
Charpin
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D015703:Antigens, CD; D001943:Breast Neoplasms / Q000098:blood supply* / Q000737:chemistry*; D000071063:Endoglin; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D015999:Multivariate Analysis; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis*; D011237:Predictive Value of Tests; D011379:Prognosis; D042787:Receptor, TIE-2 / Q000032:analysis*; D011956:Receptors, Cell Surface; D016019:Survival Analysis; D013997:Time Factors; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis*
D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011956:Receptors, Cell Surface; D019010:Vascular Cell Adhesion Molecule-1; D042787:Receptor, TIE-2