Expression of CD95 (Fas) in sun-exposed human skin and cutaneous carcinomas.
BACKGROUND
Carcinomas of the skin are by far the most common human malignancies. Continuous exposure to ultraviolet (UV) light facilitates the development of precancerous lesions (actinic keratosis [AK]) that may progress to invasive squamous carcinomas. Apoptosis, triggered by the activation of CD95 (Fas), is one of the most important defense mechanisms against UV light-induced carcinogenesis in experimental models, but the dynamics of CD95 expression in patients with sun-induced lesions are largely unknown.


METHODS
The authors studied the expression of CD95 (Fas) in biopsy samples of normal skin (not exposed to sun) and compared it with chronically sun-exposed skin (as evidenced by solar elastosis), AK, squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), and keratoacanthomas (KA).


RESULTS
Normal skin keratinocytes expressed CD95 in cytoplasmic membranes and intercellular bridges in the basal layer. In chronically sun-exposed keratinocytes (solar elastosis, no evidence of dysplasia), CD95 expression was up-regulated and was observed throughout the entire thickness of the epidermis. However, in actinic keratosis there was a complete absence of Fas in approximately two-thirds of the cases (8 of 12). In invasive SCC, CD95 was expressed focally and weakly only at the sites of contact with stromal lymphocytes. Keratoacanthomas consistently expressed CD95 at the interface with the inflammatory cells. No staining was observed in BCC.


CONCLUSIONS
CD95 (Fas) up-regulation in chronically sun-exposed keratinocytes indicates an important role in the control of sun-induced damage. Further sun exposure results, however, in significant down-regulation of this defense mechanism, proportional to the degree of dysplasia.
Filipowicz
Ewa
E
Division of Surgical Pathology, Department of Pathology, University of Texas Medical Branch, Galveston, Texas 77555-0588, USA.
Adegboyega
P
P
Sanchez
R L
RL
Gatalica
Zoran
Z
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002280:Basal Cell Carcinoma / Q000235:genetics* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D002471:Cell Transformation, Neoplastic; D002648:Child; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn; D015603:Keratinocytes / Q000473:pathology; D007636:Keratoacanthoma / Q000235:genetics* / Q000473:pathology; D007642:Keratosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010787:Photosensitivity Disorders / Q000235:genetics* / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D013472:Sunlight / Q000009:adverse effects*; D015854:Up-Regulation; D019014:fas Receptor / Q000096:biosynthesis*
D019014:fas Receptor