title: The relationship of the neo-angiogenic marker, endoglin, with response to neoadjuvant chemotherapy in breast cancer.
abstract: Endoglin (CD105) is upregulated in endothelial cells of tissues undergoing neovascularisation. A greater number of CD105-positive vessels predicts poor survival in breast cancer. We examine whether CD105 expression predicts response to neoadjuvant chemotherapy. Fifty-seven women (median age 50 years, range 29-70) received neoadjuvant chemotherapy for operable breast cancer. Immunohistochemical staining using monoclonal antibodies to CD105 and CD34 was performed on pretreatment biopsies and post-treatment surgical specimens. Individual microvessels were counted in 10 random fields at x 200 magnification. Median counts were correlated with clinical and pathological response using the Mann-Whitney U-test. Forty-five out of fifty-seven patients (79%) responded clinically, 22 (39%) responded pathologically. On pretreatment biopsies, clinical responders had significantly lower median CD105-positive vessel counts than nonresponders (median counts 5 and 9.3/high-power field (hpf), median difference=4.0/hpf, 95% CI 0.5-8.0/hpf, P=0.02). For pathological responders and nonresponders, median counts were 4.8 and 5.5/hpf (median difference -0.5/hpf, 95% CI=-2.5-2.0/hpf, P=0.77). CD34 expression (total microvessel density) did not correlate with response. Pretreatment CD105 expression predicts for clinical response to chemotherapy, with a lower initial count being favourable. Patients with high baseline new vessel counts or increased counts after conventional therapy may benefit from additional antiangiogenic therapy.
authors.affiliation: Academic Oncology Unit, Mount Vernon Cancer Centre, Northwood, Middlesex, HA6 2RN, UK. mjberesford@yahoo.co.uk
authors.forename: M J
authors.initials: MJ
authors.lastname: Beresford
authors.forename: A L
authors.initials: AL
authors.lastname: Harris
authors.forename: M
authors.initials: M
authors.lastname: Ah-See
authors.forename: F
authors.initials: F
authors.lastname: Daley
authors.forename: A R
authors.initials: AR
authors.lastname: Padhani
authors.forename: A
authors.initials: A
authors.lastname: Makris
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D000071063:Endoglin; D005260:Female; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D011446:Prospective Studies; D011956:Receptors, Cell Surface / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface