STAT3 as a Biomarker of Progression in Atypical Nevi of Patients with Melanoma: Dose–Response Effects of Systemic IFNα Therapy  Wenjun Wang, Howard D. Edington, Uma N.M. Rao, Drazen M. Jukic, Hong Wang, Janice M. Shipe-Spotloe, John M. Kirkwood  Journal of Investigative Dermatology  Volume 128, Issue 8, Pages 1997-2002 (August 2008) DOI: 10.1038/jid.2008.26 Copyright © 2008 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Photographic documentation for the study of multiple nevi. Patients with multiple nevi larger than 4mm diameter and a history of primary cutaneous melanoma are eligible for two separate studies. Four nevus lesions (a–d) were selected randomly for study. Two of them were chosen randomly to be resected before LDI or HDI treatment. The remaining two nevi were resected post-LDI or HDI therapy. Journal of Investigative Dermatology 2008 128, 1997-2002DOI: (10.1038/jid.2008.26) Copyright © 2008 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 The pattern of expression of pSTAT1 and pSTAT3 in nevus. The baseline expression levels of pSTAT1 and pSTAT3 were observed in this prospective study. With the maturing of melanocytes from the epidermal junction to the deep dermis, the expression of pSTAT3 (red chromogen) was decreased, whereas the expression of pSTAT1 (blue chromogen) was increased. (a) Taken by × 10 objective. (b) The amplification of junctional melanocytes and (c) the amplification of dermal melanocytes. The pSTAT3 expression level is higher in junctional melanocytes than that in deep dermal melanocytes, whereas pSTAT1 expression level is higher in deep dermal melanocytes than that in junctional melanocytes. Journal of Investigative Dermatology 2008 128, 1997-2002DOI: (10.1038/jid.2008.26) Copyright © 2008 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 3 The expression of pSTAT3 is positively associated with the severity of atypia. The baseline expression level of pSTAT3 is positively associated with the degree of atypia in nevi, n=57, r=0.50, P<0.0001. Zero represents no atypia (n=12); 1, mild atypia (n=38); and 2, moderate atypia (n=7). The bar inside the box represents the median. Journal of Investigative Dermatology 2008 128, 1997-2002DOI: (10.1038/jid.2008.26) Copyright © 2008 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 4 pSTAT1 and pSTAT3 immunohistochemistry of nevi. (a and b) The pre- and post-treatment with LDI, show that LDI downregulates pSTAT3 (red color) and upregulates pSTAT1 (blue color). (c and d) The pre- and post-treatment with HDI, show that HDI downregulates pSTAT3 (red color) and upregulates pSTAT1 (blue color) to a greater extent than LDI. Journal of Investigative Dermatology 2008 128, 1997-2002DOI: (10.1038/jid.2008.26) Copyright © 2008 The Society for Investigative Dermatology, Inc Terms and Conditions