Radiogenic lymphangiogenesis in the skin

Susanne Jackowski, Matthias Janusch, Eckhard Fiedler, Wolfgang C. Marsch, Eva J. Ulbrich, Gabriele Gaisbauer, Jürgen Dunst, Dontscho Kerjaschki, Peter Helmbold*

*Corresponding author for this work
35 Citations (Scopus)


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 μm) 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.

Original languageEnglish
JournalAmerican Journal of Pathology
Issue number1
Pages (from-to)338-348
Number of pages11
Publication statusPublished - 07.2007


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