Squamous-Cell Carcinoma of the Scalp Arising in Lesions of Discoid Lupus Erythematosus

Sulica, Virginia I.; Kao, Grace F.

doi:10.1097/00000372-198804000-00007

Cited by 50 publications

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“…4 and M.v.H., unpublished results). Furthermore, inflammation and chronic wounds are associated with development of human SCC, as in the development of SCC in burn scars, chronic venous stasis ulcers, and discoid lupus erythematosus (28)(29)(30). Progression of actinic keratosis to SCC has recently also been shown to be associated with an inflammatory stage (31).…”

Section: Discussionmentioning

confidence: 99%

Tumor necrosis factor receptor 1-mediated signaling is required for skin cancer development induced by NF-κB inhibition

Lind

Rozell²,

Wallin³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

105

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T he Rel͞NF-B transcription factors have a central role in several cellular processes, including proliferation, cell adhesion, apoptosis, and regulation of the immune response (1). Under nonstimulating conditions, NF-B is retained in the cytoplasm in an inactive form because of its interaction with the inhibitory proteins I Bs. In response to an activating stimulus, I B is phosphorylated by an I B kinase (IKK) complex, which targets it for degradation by the proteasome, releasing NF-B, which translocates to the nucleus, where it regulates the transcription of target genes.Evidence gathered from studies during recent years have shown that NF-B has a growth inhibitory function in the skin. Initial studies showed that overexpression of the NF-B subunits p50 or p65 in the basal layer of the murine epidermis by using a keratin 14 (K14) promoter leads to hypoplasia of the epidermis, whereas expression of a superrepressor form of the inhibitor of NF-B type ␣ (I B␣) results in hyperplasia (2). Although K14-I B␣ mice die shortly after birth (day 7), we have shown that mice with keratin 5 (K5)-directed expression of I B␣ (K5-I B␣) to the basal layer of the epidermis survive to adulthood (3). Not only do these mice develop hyperplasia of the epidermis, but the skin phenotype of K5-I B␣ mice is also characterized by an intense neutrophil-dominated inflammation of the skin and an early development of squamous cell carcinomas (SCC).Recent data suggest that human sporadic SCC may show a block in NF-B signaling based on nuclear exclusion of the RelA NF-B subunit (ref. 4 and M.v.H., unpublished results). Furthermore, it was recently shown that coexpression of a superrepressor form of I B␣ and Ha-Ras results in neoplasia resembling invasive SCC in human keratinocytes transplanted to severe combined immunodeficient (scid͞scid) mice, supporting the relevance of a NF-B block in the induction of human SCC (4).Inflammation of the skin with neutrophil infiltration and hyperproliferation is also seen in female heterozygous Ikk␥-deficient mice, which develop a condition similar to the human X-linked disorder Incontinentia Pigmenti (IP) (5, 6). IKK␥ is the regulatory subunit of the IKK complex, which, in addition, contains the two catalytic subunits IKK␣ (IKK1) and IKK␤ (IKK2) (1). It is now well established that human IP results from loss-of-function mutations in the IKK␥ gene (7). Interestingly, subungual keratoacanthoma-like tumors and cases of SCC have been reported as late manifestations of IP (8-11).The catalytic IKK␤ subunit is necessary for activation of NF-B in response to proinflammatory stimuli (1). Skin-specific deletion of the IKK␤ gene, K14-Cre͞Ikk2 FL/FL , was recently shown to result in an inflammatory phenotype with concomitant hyperproliferation of the epidermis (12), very similar to what is seen in the K5-I B␣ mice. Because the K14-Cre͞Ikk2 FL/FL mice die between day 7 and day 9 after birth, it is currently not known whether they, similar to K5-I B␣ mice, are prone to develop SCC.Besides inf lammation and hyperprolifera...

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Section: Discussionmentioning

confidence: 99%

Tumor necrosis factor receptor 1-mediated signaling is required for skin cancer development induced by NF-κB inhibition

Lind

Rozell²,

Wallin³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

105

View full text Add to dashboard Cite

show abstract

“…42 SCC arising in patients with DLE affects all skin types and is a potentially lifethreatening occurrence, with Sulica and Kao reporting a metastatic rate of 31% and ensuing death in 10.5%. 61 A low threshold for biopsy of persistent, treatment-resistant hyperkeratotic or ulcerated foci, classically arising in long-standing lesions of DLE, and prompt, aggressive management are mandatory. Other associated diseases include secondary verruciform xanthoma, 62 papulonodular dermal mucinosis, 63 and alopecia areata.…”

Section: Discoid Lupus Erythematosusmentioning

confidence: 99%