Expression of protein mediators of type I interferon signaling in human squamous cell carcinoma of the skin

IFN-based therapy has been shown to be active in the treatment of squamons cell carcinoma (SCC) of the skin and has promise for chemoprevention and tr eatment of several other cancers. In an effort to better understand the mol ecular mechanism of this activity, we have determined the expression patter n of several of the protein mediators of type I IFN signaling by immunohist ochemistry in cutaneous SCC, SCC metastases, and adjacent nonmalignant epit helium from patient biopsies. All of the proteins, signal transducer and ac tivator of transcription (STAT) 1 alpha/beta, STAT2, p48, STAT3 alpha, and STAT3 beta, are expressed at varying levels in the adjacent epidermis, as w ell as In other epidermal and dermal cell types. For the majority of sample s tested, the expression of one or more of these proteins was reduced in SC C primary tumors compared with the adjacent nonmalignant epithelial cells, as determined by manual scoring. Quantitative densitometry of several sampl es revealed differences that are statistically significant. Our study provi des the first direct evidence for the expression of the IFN-stimulated gene factor 3 (STAT1 alpha/beta, STAT2, and p48) and STAT3 alpha and STAT3 beta mediators of IFN-alpha/beta signaling in human skin and skin-derived SCCs, These data have led to the hypothesis that the loss of IPN sensitivity may contribute to the development and progression of skin SCC.