BACKGROUND: A number of experimental studies have substantiated changes in angiogenesis and in laminin/laminin-receptor interactions during tumorigenesis and tumor progression. However, these observations have never been verified objectively in tissues from a well-defined model of tumor progression. METHODS: Tissues from 97 proliferative lesions of the melanocyte lineage defining distinct steps in tumor progression were investigated immunohistochemically for changes in angiogenesis and expression of the laminin receptor (67-kilodalton molecule). RESULTS: Although the microvessel number was low in common nevi, it increased significantly in nevi with architectural disorder with varying degrees of melanocytic atypia (termed "nevi with ADMA"), and these changes persisted during transformation. Progression to primary melanomas was accompanied by a high microvessel number and progression to metastases by another significant increase. The number and diameter of microvessels were significantly higher at the lesion base than at the adjacent dermis of primary melanomas and higher in the lesion than in the adjacent tissue of metastatic foci. Expression of the laminin receptor, evaluated as percentages of positive lesions and positive cells per lesion, underwent upregulation in the course of progression. Changes in expression were associated mostly with nevi with ADMA, transformation, and deepening of the tumors into the dermis. CONCLUSIONS: These in situ data suggest that more frequent interactions between melanocytic cells and their microvasculature via adhesion protein laminin occur during tumor progression.
BACKGROUND: A number of experimental studies have substantiated changes in angiogenesis and in laminin/laminin-receptor interactions during tumorigenesis and tumor progression. However, these observations have never been verified objectively in tissues from a well-defined model of tumor progression. METHODS: Tissues from 97 proliferative lesions of the melanocyte lineage defining distinct steps in tumor progression were investigated immunohistochemically for changes in angiogenesis and expression of the laminin receptor (67-kilodalton molecule). RESULTS: Although the microvessel number was low in common nevi, it increased significantly in nevi with architectural disorder with varying degrees of melanocytic atypia (termed "nevi with ADMA"), and these changes persisted during transformation. Progression to primary melanomas was accompanied by a high microvessel number and progression to metastases by another significant increase. The number and diameter of microvessels were significantly higher at the lesion base than at the adjacent dermis of primary melanomas and higher in the lesion than in the adjacent tissue of metastatic foci. Expression of the laminin receptor, evaluated as percentages of positive lesions and positive cells per lesion, underwent upregulation in the course of progression. Changes in expression were associated mostly with nevi with ADMA, transformation, and deepening of the tumors into the dermis. CONCLUSIONS: These in situ data suggest that more frequent interactions between melanocytic cells and their microvasculature via adhesion protein laminin occur during tumor progression.
Authors: Dorota Gebarowska; Alan W Stitt; Thomas A Gardiner; Patrick Harriott; Brett Greer; John Nelson Journal: Am J Pathol Date: 2002-01 Impact factor: 4.307