Ann Lab Med.  2015 Nov;35(6):563-569. 10.3343/alm.2015.35.6.563.

Adverse Prognostic Impact of Bone Marrow Microvessel Density in Multiple Myeloma

• Lee N
• Lee H
• Moon SY
• Sohn JY
• Hwang SM
• Yoon OJ
• Youn HS
• Eom HS
• Kong SY

• KMID: 2363258
• DOI: http://doi.org/10.3343/alm.2015.35.6.563

Abstract

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 beta2-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.

Keyword

Multiple myeloma; Bone marrow; Angiogenesis; Microvessel; Immunohistochemistry; CD34; Progression-free survival

MeSH Terms

Aged
Antigens, CD34/metabolism
Bone Marrow/metabolism/*pathology
Disease-Free Survival
Female
Humans
Immunohistochemistry
Kaplan-Meier Estimate
Male
Microvessels/*physiopathology
Middle Aged
Multiple Myeloma/*diagnosis/mortality
Neoplasm Staging
Neovascularization, Pathologic
Plasma Cells/cytology
Prognosis
Proportional Hazards Models
Regression Analysis
Risk Factors
Antigens, CD34

Figure

• 

  Fig. 1 Assessment of microvessel density in the bone marrow by performing anti-CD34 immunohistochemical staining. (A) A 'hot spot' observed under low magnification (×100) indicated by a red circle. (B) Stained vessels, including small arterioles and venules, observed under high magnification (×400). In this slide, the number of vessels was 64/HPF.

• 

  Fig. 2 Kaplan-Meier analysis of (A) progression-free survival (PFS) and (B) overall survival in patients with low, intermediate, and high microvessel densities (MVDs). PFS was significantly shorter in patients with high MVD than in those with low MVD (P=0.025).

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