ABSTRACT
Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) represent the 2 most common types of nonmelanoma skin cancer. Both derive from keratinocytes but show a distinct biological behavior. Here we present transcriptional profiling data of a large cohort of tumor patients (SCC, n = 42; BCC, n = 114). Differentially expressed genes reflect known features of SCC and BCC including the typical cytokeratin pattern as well as upregulation of characteristic cell proliferation genes. Additionally, we found increased expression of interferon (IFN)-regulated genes (including IFI27, IFI30, Mx1, IRF1 and CXCL9) in SCC, and to a lower extent in BCC. The expression of IFN-regulated genes correlated with the extent of the lesional immune-cell infiltrate. Immunohistological examinations confirmed the expression of IFN-regulated genes in association with a CXCR3+ cytotoxic inflammatory infiltrate on the protein level. Of note, a small subset of SCC samples with low expression of IFN-regulated genes included most organ transplant recipients receiving immunosuppressive medication. Collectively, our findings support the concept that IFN-associated host responses play an important role in tumor immunosurveillance in the skin.
Subject(s)
Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/immunology , Gene Expression Regulation, Neoplastic/genetics , Interferons/immunology , Skin Neoplasms/genetics , Skin Neoplasms/immunology , Transcription, Genetic/genetics , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/pathology , Cell Differentiation , Cell Proliferation , Female , Gene Expression Profiling , Humans , Immunohistochemistry , Keratins/genetics , Male , Middle Aged , Neoplasm Invasiveness/genetics , Neoplasm Invasiveness/immunology , Neoplasm Invasiveness/pathology , Neoplasms, Basal Cell/genetics , Neoplasms, Basal Cell/immunology , Neoplasms, Basal Cell/pathology , Skin Neoplasms/pathologyABSTRACT
Here, we present data of a gene expression profiling approach to apply the diagnostic value and pathological significance of this method in different inflammatory skin diseases, using whole skin biopsies. Initially, SAGE was performed to identify frequent tags differentially expressed in various skin diseases. On the basis of these results, a new skin pathology-oriented PIQOR microarray was designed. Lichen planus (LP) was chosen as a model disease to evaluate this system. Controls included healthy skin, atopic dermatitis (AD), and psoriasis (Pso). Gene expression analyses using the topic-defined microarray followed by unclassified clustering was able to discriminate LP from AD and Pso. Genes significantly expressed in LP included type I IFN inducible genes and a specific chemokine expression pattern. The CXCR3 ligand, CXCL9, was the most significant marker for LP. In situ hybridization and immunohistochemistry confirmed the results and revealed that keratinocytes are type I IFN producers in LP skin lesions. Our results show that gene expression profiling using a skin-specific microarray is a reliable method to identify patients with LP in the chosen context and reflect recent models concerning the pathogenesis of this disease. Gene expression profiling might complement the diagnostic spectrum in dermatology and may provide new pathogenetic insights.
