Altered proliferation and differentiation of human epidermis in cases of skin fibrosis after radiotherapy.
OBJECTIVE
To characterize, at the histopathologic and molecular levels, the irradiated epidermis in cases of human skin fibrosis induced by radiotherapy.


METHODS
Surgical samples were obtained from 6 patients who had developed cutaneous fibronecrotic lesions from 7 months to 27 years after irradiation. The proliferation and differentiation status of the irradiated epidermis was characterized with specific markers using immunohistochemical methods.


RESULTS
All samples presented with hyperplasia of the epidermis associated with local inflammation. The scar epidermis exhibited an increased expression of proliferating cell nuclear antigen, which revealed hyperproliferation of keratinocytes. Furthermore, an abnormal differentiation was found, characterized by the expression of K6 and K16, and by alterations in protein amounts and localization of cytokeratins, involucrin, and transforming growth factor-beta1.


CONCLUSIONS
These results demonstrate that late damage of irradiated skin is not only characterized by fibrosis in the dermis but also by hyperplasia in the epidermis. This hyperplasia was due to both hyperproliferation and abnormal differentiation of keratinocytes.
Sivan
Virginie
V
Service de Génomique Fonctionnelle, CEA, DSV, DRR, Evry, France.
Vozenin-Brotons
Marie-Catherine
MC
Tricaud
Yves
Y
Lefaix
Jean-Louis
JL
Cosset
Jean-Marc
JM
Dubray
Bernard
B
Martin
Michèle T
MT
D000328:Adult; D000368:Aged; D002454:Cell Differentiation / Q000528:radiation effects; D002455:Cell Division / Q000528:radiation effects; D002921:Cicatrix / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D006965:Hyperplasia / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D016023:Integrins / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D007633:Keratins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011832:Radiation Injuries / Q000378:metabolism / Q000473:pathology*; D012867:Skin / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D016212:Transforming Growth Factor beta / Q000378:metabolism
D016023:Integrins; D018809:Proliferating Cell Nuclear Antigen; D016212:Transforming Growth Factor beta; D007633:Keratins