Cutaneous squamous cell carcinoma (SCC) occurs commonly and can metastasize. Identification of specific molecular aberrations and mechanisms underlying the development and progression of cutaneous SCC may lead to better prognostic and therapeutic approaches and more effective chemoprevention strategies. To identify genetic changes associated with early stages of cutaneous SCC development, we analyzed a series of 40 archived skin tissues ranging from normal skin to invasive SCC. Using high-resolution array-based comparative genomic hybridization, we identified deletions of a region on chromosome 10q harboring the INPP5A gene in 24% of examined SCC tumors. Subsequent validation by immunohistochemistry on an independent sample set of 71 SCC tissues showed reduced INPP5A protein levels in 72% of primary SCC tumors. Decrease in INPP5A protein levels seems to be an early event in SCC development, as it also is observed in 9 of 26 (35%) examined actinic keratoses, the earliest stage in SCC development. Importantly, further reduction of INPP5A levels is seen in a subset of SCC patients as the tumor progresses from primary to metastatic stage. The observed frequency and pattern of loss indicate that INPP5A, a negative regulator of inositol signaling, may play a role in development and progression of cutaneous SCC tumors.
To provide an overview of 1) traditional methods of skin cancer early detection, 2) current technologies for skin cancer detection, and 3) evolving practice models of early detection.
Clinical and laboratory observations suggest that host immunological responses may occasionally influence the course of melanoma, stimulating the investigation of immunotherapy approaches in this disease. Areas of active investigation have included recombinant cytokines, either alone or in combination with chemotherapeutic regimens or other biological response modifiers, such as vaccines, monoclonal antibodies, dendritic cells and gene therapy. To date, the benefit of these approaches in patients at high-risk of recurrence or advanced disease has been modest. Although many of these novel strategies are limited by weak antigen presentation, tumor-induced tolerance and tumor heterogeneity, it is possible that these approaches will prove more useful when given in combination.