Faculty Bibliography

A 67-year-old man with a three-year history of non-scarring alopecia that progressed to alopecia totalis despite intralesional glucocorticoid injections is presented. He developed 20-nail dystrophy that was recalcitrant to antifungal and anti-inflammatory treatments. Biopsy of the nail matrix showed histopathologic features of lichen planus. Alopecia totalis and isolated lichen planus of the nails are uncommon subtypes of common dermatologic disorders. Rarely reported concurrently, we provide a review of the literature of their association, which is most likely attributed to their autoimmune pathogeneses.

Although the principles that balance stem cell self-renewal and differentiation in normal tissue homeostasis are beginning to emerge, it is still unclear whether cancer cells with tumour initiating potential are similarly governed, or whether they have acquired distinct mechanisms to sustain self-renewal and long-term tumour growth. Here we show that the transcription factor Sox2, which is not expressed in normal skin epithelium and is dispensable for epidermal homeostasis, marks tumour initiating cells (TICs) in cutaneous squamous cell carcinomas (SCCs). We demonstrate that Sox2 is required for SCC growth in mouse and human, where it enhances Nrp1/Vegf signalling to promote the expansion of TICs along the tumour-stroma interface. Our findings suggest that distinct transcriptional programmes govern self-renewal and long-term growth of TICs and normal skin epithelial stem and progenitor cells. These programmes present promising diagnostic markers and targets for cancer-specific therapies.

The precise mechanisms governing invasion at the leading edge of squamous cell carcinoma (SCC) and its subsequent metastasis are not fully understood. We aimed to define the cancer-related molecular changes that distinguish noninvasive tumor from invasive SCC. To this end, we combined laser capture microdissection with complementary DNA (cDNA) microarray analysis. We defined invasion-associated genes as those differentially regulated only in invasive SCC nests, but not in actinic keratosis or in situ SCC, compared with normal epidermis. There were 383 upregulated and 354 downregulated genes in the "invasion set." SCC invasion was characterized by aberrant expression of various proteolytic molecules. We noted increased expression of MMP7 and IL-24 in invasive SCC. IL-24 induced the expression of matrix metallopeptidase 7 (MMP7) in SCC cells in culture. In addition, blocking of MMP7 by a specific antibody significantly delayed the migration of SCC cells in culture. These results suggest a possible contribution of IL-24 to SCC invasion via enhancing focal expression of MMP7, although IL-24 has been suggested to have antitumor growth effects in other cancer types. Identification of regional molecular changes that regulate cancer invasion may facilitate the development of new targeted treatments for aggressive cancer.

The development of vismodegib and its recent approval by the United States Food and Drug Administration for use in patients with locally advanced or metastatic basal cell carcinoma (BCC) carries with it a renewed sense of optimism. Once BCC has progressed to an advanced, or so-called inoperable stage, there has been a paucity of effective therapies, making the new small molecule inhibitors targeting the hedgehog pathway particularly hopeful prospects. In order to better understand the utility of these new treatments, it is important to assess the existing economic, physical, and psychological burden of advanced BCC. This review aims to recognize the impact of inoperable and metastatic BCC, as well as to better characterize the various types of advanced BCC. The use of vismodegib as a prophylactic treatment in patients with basal cell nevus syndrome is also addressed, including possible adverse events, tumor resistance, and new onset malignancies.