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Increased Vascularization Predicts Favorable Outcome in Follicular Lymphoma

Departments of ¹ Hematology, ² Pathology, and ³ Epidemiology and Biostatistics, University Medical Centre Nijmegen, Nijmegen, the Netherlands

Requests for reprints: Ad Koster, Department of Hematology 544, University Medical Centre Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands. Phone: 31-2436-14762; Fax: 31-2435-42080; E-mail: a.koster{at}hemat.umcn.nl.

Purpose: In malignant lymphoma, angiogenesis has been associated with adverse outcome or more aggressive clinical behavior. This correlation has been established in groups of patients with a large heterogeneity regarding lymphoma subtypes and treatment regimens. The aim of this study is to investigate the significance of vascularization in patients with follicular lymphoma receiving uniform first-line treatment.

Experimental Design: We assessed microvessel density (MVD) in pretreatment lymph node biopsies of 46 previously untreated patients with follicular lymphoma using anti-CD34 immunohistochemical staining and interactive quantification. In a selection of cases, vascular endothelial growth factor (VEGF)-RNA in situ hybridization was done. Patients were treated with cyclophosphamide-vincristine-prednisone induction chemotherapy combined with IFN-2b. Thirty-six patients responded and received IFN- as maintenance therapy.

Results: MVD ranged from 10 to 70 per measurement field of 0.19 mm² (median, 38). Median progression-free survival was 47 months in patients with MVD in the highest tertile and only 13 months in patients with lower MVD. Overall survival in patients with low vessel density was 59 months. In patients with high vessel density, median overall survival was not reached. Multivariate analysis indicated that MVD was independently associated with overall survival. There was a lack of correlation between VEGF-RNA expression and vessel density.

Conclusion: This study shows that in follicular lymphoma increased vascularization is associated with improved clinical outcome. Furthermore, VEGF-A expression seems not to be involved in follicular lymphoma angiogenesis.

Key Words: Follicular lymphoma • Microvessel density • Angiogenesis • VEGF

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