Stromelysin-3 mRNA associated with myofibroblasts is overexpressed in aggressive basal cell carcinoma and in dermatofibroma but not in dermatofibrosarcoma.
Stromelysin-3 is produced in the stroma of various malignant tumors, and in breast carcinoma there seems to be a positive correlation between aggressive disease and intensity of stromelysin-3 expression, suggesting that stromelysin-3 participates in the tumor spread. In basal cell carcinoma, previous findings on stromelysin-3 have been inconclusive in this respect. Our study was undertaken to determine the pattern of stromelysin-3 production in relation to different histologic subtypes and stromal reactions in basal cell carcinoma. By in situ hybridization, stromelysin-3 mRNA was detected in stromal fibroblastic cells in 51/56 samples. Furthermore, there was a significant correlation between strong signal for stromelysin-3 mRNA and infiltrative tumor growth. In all tumors, there was ongoing collagen synthesis as shown by a signal for procollagen I mRNA; this signal co-localized with stromelysin-3 around tumor nests. Our findings suggest a link between stromelysin-3 and fibrotic stromal response, which prompted us to evaluate the expression of stromelysin-3 in other fibrotic skin tumors. Interestingly, stromelysin-3, co-localizing with procollagen I mRNA, was consistently expressed in lesional cells in dermatofibromas (19/19), but not in dermatofibrosarcomas (0/7). Thus, our results indicate that in addition to being a marker for malignant disease, stromelysin-3 is produced by fibroblastic cells associated with benign fibrosis. A subset of cells producing stromelysin-3 appears to be myofibroblasts as demonstrated by immunoreactivity for alpha smooth muscle actin in both basal cell carcinoma and dermatofibroma.
Undén
A B
AB
Department of Dermatology, Karolinska Hospital, Stockholm, Sweden.
Sandstedt
B
B
Bruce
K
K
Hedblad
M
M
Stahle-Bäckdahl
M
M
D000199:Actins / Q000378:metabolism; D002280:Basal Cell Carcinoma / Q000378:metabolism* / Q000473:pathology; D018223:Dermatofibrosarcoma / Q000378:metabolism* / Q000473:pathology; D018219:Histiocytoma, Benign Fibrous / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D053507:Matrix Metalloproteinase 11; D008666:Metalloendopeptidases / Q000235:genetics*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D011347:Procollagen / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology
D000199:Actins; D011347:Procollagen; D012333:RNA, Messenger; D053507:Matrix Metalloproteinase 11; D008666:Metalloendopeptidases