The risk of developing metastatic disease in colorectal cancer is related to CD105-positive vessel count.
OBJECTIVE
Angiogenesis is a complex multistep process that involves extracellular matrix remodeling, migration and proliferation of endothelial cells, and morphogenesis of microvessels. CD105 (endoglin), a co-receptor of the TGF-beta superfamily, was proposed as a marker of neovascularization in solid malignancies. The aim of this study was to evaluate retrospectively the effect of CD105-assessed angiogenesis on the risk of developing metastatic disease in colorectal cancer (CRC).


METHODS
One hundred and twenty-five paraffin-embedded samples were analyzed by immunohistochemical methods using a CD105 monoclonal antibody. The median follow-up was 70.8 months. Survivals were calculated from actuarial estimates, and logistic regression predicted the risk of developing metastatic disease.


RESULTS
The CD105-vessel count was strongly correlated with the occurrence of metastatic disease. The median CD105-positive vessels in patients with and without metastatic disease were 24.7 and 13.2 vessels/mm(2), respectively (P < 0.001). For each one microvessel increase in the vessels count per 400x field, there was a 1.42-fold increase in the risk of metastatic disease (P < 0.001).


CONCLUSIONS
The assessment of tumor angiogenesis with anti-CD105 was not sufficient for its use as a surrogate end point for survival because of the amount of survival variability explained was only 8% in absence of metastatic disease. In contrast, multivariate logistic regression analysis revealed that CD105-vessels count can identify patients at high risk of metastatic disease.
Romani
Antonello A
AA
Dipartimento di Medicina Sperimentale, Sezione di Patologia Molecolare ed Immunologia, Università degli Studi di Parma, Italy.
Borghetti
Angelo F
AF
Del Rio
Paolo
P
Sianesi
Mario
M
Soliani
Paolo
P
D000230:Adenocarcinoma / Q000098:blood supply* / Q000556:secondary* / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis* / Q000276:immunology; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000098:blood supply* / Q000473:pathology* / Q000601:surgery; D000071063:Endoglin; D042783:Endothelial Cells / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000473:pathology*; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000276:immunology; D012044:Regression Analysis; D012189:Retrospective Studies
D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface