Radiogenic lymphangiogenesis in the skin.
The time course of microvascular changes in the environment of irradiated tumors was studied in a standardized human protocol. Eighty skin biopsies from 40 patients with previously treated primary breast cancer were taken from irradiated skin and corresponding contralateral unirradiated control areas 2 to 8 weeks, 11 to 14 months, or 17+ months after radiotherapy (skin equivalent dose 30 to 40 Gy). Twenty-two biopsies of 11 melanoma patients who had undergone lymph node dissection were used for unirradiated control. We found an increase of total podoplanin(+) lymphatic microvessel density resulting mainly from a duplication of the density of smallest lymphatic vessels (diameter <10 microm) in the samples taken 1 year after radiation. Our findings implicate radiogenic lymphangiogenesis during the 1st year after therapy. The numbers of CD68(+) and vascular endothelial growth factor-C(+) cells were highly elevated in irradiated skin in the samples taken 2 to 8 weeks after radiotherapy. Thus, our results indicate that vascular endothelial growth factor-C expression by invading macrophages could be a pathogenetic route of induction of radiogenic lymphangiogenesis.
Jackowski
Susanne
S
Department of Dermatology, University of Heidelberg, Heidelberg, Germany.
Janusch
Matthias
M
Fiedler
Eckhard
E
Marsch
Wolfgang C
WC
Ulbrich
Eva J
EJ
Gaisbauer
Gabriele
G
Dunst
Jürgen
J
Kerjaschki
Dontscho
D
Helmbold
Peter
P
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001943:Breast Neoplasms / Q000532:radiotherapy / Q000601:surgery; D005260:Female; D006801:Humans; D042583:Lymphangiogenesis / Q000528:radiation effects*; D042601:Lymphatic Vessels / Q000528:radiation effects; D008297:Male; D008545:Melanoma / Q000098:blood supply / Q000473:pathology; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D011878:Radiotherapy / Q000009:adverse effects*; D012867:Skin / Q000528:radiation effects*; D012878:Skin Neoplasms / Q000098:blood supply / Q000473:pathology; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism; D042643:Vascular Endothelial Growth Factor D / Q000378:metabolism; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D; C067980:CD68 antigen, human; D000097382:CD68 Molecule