What is the role of angiogenesis in metastasis from cutaneous melanoma?

Abstract

BRESLOW first proposed in 1970 that a cutaneous melanoma with a thickness of less than 0.76 mm was associated with low metastatic rate and high curability [ 11. The paper raised two questions in the minds of oncologists: (i) Would such a sharp breakpoint continue to hold up, or would its range and standard deviation gradually increase as subsequent authors reported their experiences? (ii) Why should a minute change of tumor thickness be responsible for such a sharp delineation between low and high metastatic rate? The first question generated clinical studies from melanoma centers throughout the world. More than a decade-and-a-half later, it is clear that Breslow’s prediction has stood the test of time. Tumor thickness remains the single most important indicator of prognosis in patients with cutaneous melanoma of the nodular or superficial spreading type [2]. Also, a thickness of 0.76 mm or less continues to correlate with the lowest metastatic rate, occasional proposals to modify this measurement notwithstanding [3]. The second question remained an enigma until the mid-1970’s when experiments by Folkman and his associates demonstrated that tumors begin their growth in an avascular (or prevascular) phase followed by a vascular phase in which further tumor growth is angiogenesis-dependent [4]. In the avascular phase, growth is restricted because nutrients and catabolites can be exchanged only by simple diffusion with the existing capillary bed. In contrast, once a tumor is vascularized by new