p53 mutations in solar keratoses

Park, Won-Sang; Lee, Hun-kyung; Lee, Jung-Young; Yoo, Nam-Jin; Kim, Choo-soung; Kim, Sang-ho

doi:10.1016/s0046-8177(96)90312-3

Cited by 38 publications

(30 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Indeed, p53 gene mutations, immunopositivity of p53, and loss of heterozygosity have been predominantly observed in actinic keratosis. 21 This fi nding may provide a plausible explanation for the increased incidence and higher risk of cancer development observed in individuals with VAD. 11 Consistent with this, a recent report indicated that UV irradiation causes rapid downregulation of RARs and RXRs proteins and near-total loss of RA-responsive gene expression in human skin in vivo.…”

Section: Discussionmentioning

confidence: 82%

Enhanced expression of retinoic acid-metabolizing enzyme CYP26A1 in sunlight-damaged human skin

Osanai

Lee

2011

Med Mol Morphol

View full text Add to dashboard Cite

Vitamin A deficiency (VAD) is associated with increased susceptibility to carcinogenesis. CYP26A1, the gene encoding a cytochrome P450 enzyme specifically involved in metabolic inactivation of retinoic acid (RA), the most active vitamin A derivative, has been shown to result in a state of functional VAD of the cell. Recently, we demonstrated that CYP26A1 efficiently promotes cell survival properties and eventually contributes to the carcinogenic process, implying roles as an oncogene. To clarify the possible association between VAD caused by CYP26A1 expression and the development of human epithelial neoplasia, we examined whether enhanced expression of CYP26A1 might be observed in various lesions of human skin. We report here that basal keratinocytes showed only weak positivity of CYP26A1 in sunlight-nonexposed areas, whereas strong positive staining was observed in skin from chronically sunexposed body areas and in epidermis that had the dysplastic changes known as actinic keratosis. However, we found no expression of constitutive CYP26A1 in skin malignancies such as squamous cell carcinomas. Our observation suggests an involvement of enhanced CYP26A1 expression causing a functional VAD state in skin that can potentially lead to neoplastic transformation of keratinocytes in an early phase during skin carcinogenesis.

show abstract

Section: Discussionmentioning

confidence: 82%

Enhanced expression of retinoic acid-metabolizing enzyme CYP26A1 in sunlight-damaged human skin

Osanai

Lee

2011

Med Mol Morphol

View full text Add to dashboard Cite

show abstract

“…In our study, we have employed an anti‐p53 antibody that recognizes both mutant and wild‐type p53 protein. Therefore, it is not possible to determine whether the observed increase in p53 immunoexpression corresponds to the overexpression of non‐functional p53 protein or if it represents the accumulation of the wild‐type form, stabilized due to the insufficient production of p53 regulators 4,10–13,15 . However, both types of p53 accumulation suggest the genomic alteration of p53 or genes that encode negative regulators of the p53.…”

Section: Discussionmentioning

confidence: 99%

“…The proapoptotic protein, p53, is upregulated in injured cells because p53 maintains genomic stability through the regulation of cell cycle arrest, repair, and apoptosis 9 . In AK and skin carcinomas, p53 has been found to be overexpressed 9–15 . The human p53‐like gene family also includes p63, which encodes a series of proteins that promote or suppress p53‐related functions 16 .…”

mentioning

confidence: 99%

Expression of apoptotic, cell proliferation regulatory, and structural proteins in actinic keratosis and their association with dermal elastosis

Silva¹,

Coelho²,

Bocca³

et al. 2007

J Cutan Pathol

View full text Add to dashboard Cite

show abstract

“…[14][15][16] Ultraviolet-related TP53 mutations are an early event in the development of cutaneous SCC and can be detected in a proportion of AK and in situ carcinomas. [17][18][19] Increased p53 immunohistochemical staining may reflect TP53 mutation status, although other studies have shown a suboptimal correlation. [20][21][22] Recent next-generation sequencing efforts have shown Notch1 mutations in a subset of mucosal head and neck SCC, and suggested that Notch1 may act as a tumor suppressor in SCC.…”

Section: Introductionmentioning

confidence: 92%

Cutaneous Squamous Cell Carcinomas of the Lower Extremities Show Distinct Clinical and Pathologic Features

2015

View full text Add to dashboard Cite

Cutaneous squamous cell carcinomas mainly affect older, predominantly male patients. Most are due to chronic ultraviolet exposure, and associated with actinic keratoses. On the lower extremities, they occur more commonly in women. However, data on these tumors as a distinct group are scarce. We evaluated 61 squamous cell carcinomas of the lower extremities. Overall, 69% of patients were female. Mean age was 75 years. More than 90% of tumors were well differentiated, 3% showed perineural invasion, and none lymphovascular invasion. In all, 63.9% showed evidence of severe chronic sun damage. Associated actinic keratoses were identified in only 13% of cases. By contrast, 80% were associated with distinctive basal epidermal proliferations with a retiform growth pattern. These proliferations were evaluated immunohistochemically for keratinocyte stem cell markers, p53 and Notch1 in 15 cases. All cases were positive for cytokeratin 14, p53, and Notch1 (with variable intensity in the latter 2), and predominantly negative for cytokeratin 19. Interestingly, basal retiform proliferations were positive for cytokeratin 15 in 66% of cases. Fifteen head and neck squamous cell carcinomas were evaluated in comparison. Those lacked associated basal retiform proliferations except in 1 case. In contrast, 87% were associated with actinic keratoses and 100% with severe chronic sun damage. Actinic keratoses associated with head and neck tumors showed cytokeratin 15 staining only in 7% of cases (P = .003 compared with cytokeratin 15 in basal retiform proliferations associated with leg carcinomas). These findings support the hypothesis that lower extremity squamous cell carcinomas are distinct and may exhibit a pathogenesis less reliant on actinic damage.

show abstract

p53 mutations in solar keratoses

Cited by 38 publications

References 24 publications

Enhanced expression of retinoic acid-metabolizing enzyme CYP26A1 in sunlight-damaged human skin

Enhanced expression of retinoic acid-metabolizing enzyme CYP26A1 in sunlight-damaged human skin

Expression of apoptotic, cell proliferation regulatory, and structural proteins in actinic keratosis and their association with dermal elastosis

Cutaneous Squamous Cell Carcinomas of the Lower Extremities Show Distinct Clinical and Pathologic Features

Contact Info

Product

Resources

About