Adverse prognostic impact of bone marrow microvessel density in multiple myeloma.
BACKGROUND
Angiogenesis is important for the proliferation and survival of multiple myeloma (MM) cells. Bone marrow (BM) microvessel density (MVD) is a useful marker of angiogenesis and is determined by immunohistochemical staining with anti-CD34 antibody. This study investigated the prognostic impact of MVD and demonstrated the relationship between MVD and previously mentioned prognostic factors in patients with MM.


METHODS
The study included 107 patients with MM. MVD was assessed at initial diagnosis in a blinded manner by two hematopathologists who examined three CD34-positive hot spots per patient and counted the number of vessels in BM samples. Patients were divided into three groups according to MVD tertiles. Cumulative progression-free survival (PFS) and overall survival (OS) curves, calculated by using Kaplan-Meier method, were compared among the three groups. Prognostic impact of MVD was assessed by calculating Cox proportional hazard ratio (HR).


RESULTS
Median MVDs in the three groups were 16.8, 33.9, and 54.7. MVDs were correlated with other prognostic factors, including β2-microglobulin concentration, plasma cell percentage in the BM, and cancer stage according to the International Staging System. Multivariate Cox regression analysis showed that high MVD was an independent predictor of PFS (HR=2.57; 95% confidence interval, 1.22-5.42; P=0.013). PFS was significantly lower in the high MVD group than in the low MVD group (P=0.025). However, no difference was observed in the OS (P=0.428).


CONCLUSIONS
Increased BM MVD is a marker of poor prognosis in patients newly diagnosed with MM. BM MVD should be assessed at the initial diagnosis of MM.
Department of Laboratory Medicine, Center for Diagnostic Oncology, Hospital and Research Institute, National Cancer Center, Goyang, Korea.|Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Korea.
Nuri
N
Lee
Hematologic Oncology Clinic, Center for Specific Organs Cancer, Hospital and Research Institute, National Cancer Center, Goyang, Korea.
Hyewon
H
Lee
Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Korea.
Soo Young
SY
Moon
Department of Laboratory Medicine, Center for Diagnostic Oncology, Hospital and Research Institute, National Cancer Center, Goyang, Korea.
Ji Yeon
JY
Sohn
Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
Sang Mee
SM
Hwang
Department of Laboratory Medicine, Center for Diagnostic Oncology, Hospital and Research Institute, National Cancer Center, Goyang, Korea.
Ok Jin
OJ
Yoon
Department of Laboratory Medicine, Center for Diagnostic Oncology, Hospital and Research Institute, National Cancer Center, Goyang, Korea.
Hye Sun
HS
Youn
Hematologic Oncology Clinic, Center for Specific Organs Cancer, Hospital and Research Institute, National Cancer Center, Goyang, Korea. hseom@ncc.re.kr.
Hyeon Seok
HS
Eom
Research Institute, Translational Epidemiology Branch, National Cancer Center, Goyang, Korea.|Department of Laboratory Medicine, Center for Diagnostic Oncology, Hospital and Research Institute, National Cancer Center, Goyang, Korea. ksy@ncc.re.kr.
Sun Young
SY
Kong
D000368:Aged; D018952:Antigens, CD34 / Q000378:metabolism; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D055806:Microvessels / Q000503:physiopathology*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis* / Q000401:mortality; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic; D010950:Plasma Cells / Q000166:cytology; D011379:Prognosis; D016016:Proportional Hazards Models; D012044:Regression Analysis; D012307:Risk Factors
D018952:Antigens, CD34
Angiogenesis; Bone marrow; CD34; Immunohistochemistry; Microvessel; Multiple myeloma; Progression-free survival