Increased laser Doppler flow in skin tumors corresponds to elevated vessel density and reactive hyperemia

Tumor angiogenesis plays a key role in tumor growth and formation of metastasis. Quantitative analysis of tumor blood flow is a prerequisite for developing novel treatment strategies such as antiangiogenic and antivascular treatment options. Laser Doppler flow in malignant melanomas has been shown to be increased compared with normal skin and melanocytic nevi. This study investigated whether this phenomenon is originated by elevated blood vessel density or by reactive hyperemia.

Laser Doppler flow was studied in 35 melanocytic nevi, 22 malignant melanomas and three basal cell carcinomas. After excision digital imaging analysis was performed in microtome sections (factor VIII-associated antigen and CD 31 labelled). The ratio of vessel area in histological sections from tumor tissue and in non-lesional skin was calculated and related to Doppler flow values.

Malignant melanomas demonstrated an enlargement of vessel cross-sectional area by factor 3.7+/-1.9 and of Doppler flow by factor 10.56+/-10.7, and melanocytic nevi accomplished increase of vessel cross-sectional area by factor 1.7+/-0.9 and of Doppler flow by factor 2.7+/-3.5.

The laser Doppler flow is influenced by the number and the velocity of erythrocytes in the tissue. The greater increase of laser Doppler flow than of vessel density in histological sections demonstrates that the flow signal in skin tumors is caused by neovascularization as well as by functional hyperemia. Laser Doppler perfusion imaging is a useful method for non-invasive, repeated and quantitative assessment of tumor vascular network and effects of antiangiogenic treatment directed vs. tumor vasculature in vivo, but it cannot distinguish between increased vessel density and reactive hyperemia.