Chronic idiopathic myelofibrosis: independent prognostic importance of bone marrow microvascular density evaluated by CD105 (endoglin) immunostaining.
Microvascular density (MVD) is substantially increased in bone marrow biopsies of patients with chronic idiopathic myelofibrosis (CIMF). CD105, a useful molecule for assessing MVD in various malignancies, is preferentially expressed by recently formed microvessels. Increased serum-soluble CD105 in patients with chronic myeloproliferative disorders, including CIMF, was documented. CD105 MVD has not so far been investigated in CIMF: to this end, the results in 55 patients with CIMF and 21 controls were compared with the conventional CD34 immunostaining as well as traditional histological and clinical disease features. The MVD mean values estimated by both CD105 and CD34 were significantly higher in CIMF patients than in controls (P<0.00001). In addition, the proportion of CD105-positive megakaryocytes was significantly higher in CIMF than in controls (P<0.0001). A degree of reticulin fibrosis >2 correlated with increased CD105 MVD (P=0.05). A multivariate analysis confirmed that CD105-positive MVD was an independent adverse prognosticator. This study demonstrates that while MVD, as assessed by both CD34 and CD105 immunostaining, is significantly increased in CIMF, only CD105-determined MVD correlates with the degree of fibrosis and is prognostically relevant. These findings provide a rationale for the investigational use of anti-CD105-targeted drugs in CIMF.
Ponzoni
Maurilio
M
Department of Pathology, San Raffaele H Scientific Institute, Milan, Italy. ponzoni.marilio@hsr.it
Savage
David G
DG
Ferreri
Andrés J M
AJ
Pruneri
Giancarlo
G
Viale
Giuseppe
G
Servida
Paolo
P
Bertolini
Francesco
F
Orazi
Attilio
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD; D018952:Antigens, CD34 / Q000032:analysis; D001808:Blood Vessels / Q000737:chemistry / Q000473:pathology*; D001853:Bone Marrow / Q000098:blood supply* / Q000473:pathology; D002908:Chronic Disease; D000071063:Endoglin; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D055728:Primary Myelofibrosis / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D011956:Receptors, Cell Surface; D016019:Survival Analysis; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis*
D015703:Antigens, CD; D018952:Antigens, CD34; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface; D019010:Vascular Cell Adhesion Molecule-1