Expression of stromal cell markers in distinct compartments of human skin cancers.
BACKGROUND
The importance of changes in the supporting tumor stroma for cancer initiation and progression is well established. The characteristics of an activated tumor stroma, however, are not completely understood. In an effort to better characterize the desmoplastic response to human skin tumors, we evaluated the expression pattern of three stromal cell markers, fibroblast-activation protein (FAP), endoglyx-1, and endosialin, in a series of melanocytic and epithelial skin tumors.


METHODS
Immunohistochemistry using antibodies against FAP, endoglyx-1, and endosialin was carried out in skin samples obtained from 43 patients. Furthermore, microarray data from an independent set of human skin cancers were analyzed.


RESULTS
FAP-positive fibroblasts were detected in all tumor tissues tested, including cases of melanocytic nevi, melanoma metastases, basal cell carcinomas, and squamous cell carcinomas. In cutaneous melanoma metastases, we identified different compartments within the stromal response on the basis of the regions of FAP expression. Endoglyx-1 expression was confined to normal and tumor blood vessel endothelium including 'hot spots' of neoangiogenesis within the cutaneous melanoma metastases. Endosialin was selectively induced in subsets of small- and medium-sized tumor blood vessels in melanoma metastases and squamous cell carcinomas.


CONCLUSIONS
These data describe novel aspects of stromal marker expression in distinct compartments of human skin tumors and may point to potential targets for novel therapeutic strategies aimed at the tumor stroma.
Huber
Margit A
MA
Department of Dermatology, Vienna Medical University, Vienna, Austria. margit.huber@meduniwien.ac.at
Kraut
Norbert
N
Schweifer
Norbert
N
Dolznig
Helmut
H
Peter
Ralf U
RU
Schubert
Roland D
RD
Scharffetter-Kochanek
Karin
K
Pehamberger
Hubert
H
Garin-Chesa
Pilar
P
D015703:Antigens, CD; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D000954:Antigens, Surface / Q000096:biosynthesis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D010450:Endopeptidases; D018093:Gelatinases; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D012697:Serine Endopeptidases / Q000096:biosynthesis / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism*; D000099167:Fibroblast Activation Protein Alpha
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D014408:Biomarkers, Tumor; D010450:Endopeptidases; D018093:Gelatinases; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha; C078203:CD248 protein, human; C089826:EMILIN3 protein, human