Cutaneous Squamous-Cell Carcinoma

Alam, Murad; Ratner, Désirée

doi:10.1056/nejm200103293441306

Cited by 1,127 publications

(1,050 citation statements)

References 81 publications

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“…SCCs are one of the most prevalent malignancies, arising in diverse body sites such as skin, mouth, esophagus, lung, and cervix. Of them, head and neck SCC (HNSCC) is the sixth leading malignancy globally 1, whereas cutaneous SCC (CSCC) is the second most common skin cancer worldwide 2.…”

Section: Introductionmentioning

confidence: 99%

Does Notch play a tumor suppressor role across diverse squamous cell carcinomas?

et al. 2016

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The role of Notch pathway in tumorigenesis is highly variable. It can be tumor suppressive or pro‐oncogenic, typically depending on the cellular context. Squamous cell carcinoma (SCC) is a cancer of the squamous cell, which can occur in diverse human tissues. SCCs are one of the most frequent human malignancies for which the pathologic mechanisms remain elusive. Recent genomic analysis of diverse SCCs identified marked levels of mutations in NOTCH1, implicating Notch signaling pathways in the pathogenesis of SCCs. In this review, evidences highlighting NOTCH's role in different types of SCCs are summarized. Moreover, based on accumulating structural information of the NOTCH receptor, the functional consequences of NOTCH1 gene mutations identified from diverse SCCs are analyzed, emphasizing loss of function of Notch in these cancers. Finally, we discuss the convergent view on an intriguing possibility that Notch may function as tumor suppressor in SCCs across different tissues. These mechanistic insights into Notch signaling pathways will help to guide the research of SCCs and development of therapeutic strategies for these cancers.

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Section: Introductionmentioning

confidence: 99%

Does Notch play a tumor suppressor role across diverse squamous cell carcinomas?

et al. 2016

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“…At present, no specific molecular markers are available for assessing the progression of premalignant actinic keratoses to invasive cutaneous squamous cell carcinoma (SCC) The incidence of melanoma and nonmelanoma skin cancer is increasing globally. [1][2][3] Nonmelanoma skin cancers, including basal cell carcinoma (approximately 80%) and squamous cell carcinoma (SCC) (approximately 20%), are among the most common cancers worldwide, and SCC has been reported as the second most common cutaneous malignancy in the white population. [1][2][3] Although early excision of cutaneous SCC is associated with a favorable outcome, for patients with metastatic disease (6%), the long-term prognosis is poor.…”

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confidence: 99%

“…[1][2][3] Nonmelanoma skin cancers, including basal cell carcinoma (approximately 80%) and squamous cell carcinoma (SCC) (approximately 20%), are among the most common cancers worldwide, and SCC has been reported as the second most common cutaneous malignancy in the white population. [1][2][3] Although early excision of cutaneous SCC is associated with a favorable outcome, for patients with metastatic disease (6%), the long-term prognosis is poor. 4 Important risk factors for cutaneous SCC include exposure to UV radiation, immunosuppression, and chronic skin ulceration.…”

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confidence: 99%

“…4 Important risk factors for cutaneous SCC include exposure to UV radiation, immunosuppression, and chronic skin ulceration. [1][2][3] An example of the latter is individuals with recessive dystrophic epidermolysis bullosa (RDEB), who often develop rapidly progressing cutaneous SCCs at sites of chronic ulceration and scarring. 5,6 At present, no specific molecular markers for progression of cutaneous SCC are available.…”

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confidence: 99%

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Serpin Peptidase Inhibitor Clade A Member 1 (SerpinA1) Is a Novel Biomarker for Progression of Cutaneous Squamous Cell Carcinoma

Farshchian

Kivisaari

Ala-aho

et al. 2011

The American Journal of Pathology

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The incidence of keratinocyte-derived nonmelanoma skin cancers is increasing worldwide because of cumulative recreational exposure to sunlight. At present, no specific molecular markers are available for assessing the progression of premalignant actinic keratoses to invasive cutaneous squamous cell carcinoma (SCC). We examined the role of the Serpin family in skin SCCs. Expression profiling of cutaneous SCC cell lines (n ‫؍‬ 8) revealed up-regulation of SerpinA1 compared with normal epidermal keratinocytes (n ‫؍‬ 5). Analysis with quantitative RT-PCR showed that the mean level of SerpinA1 mRNA was markedly up-regulated in cutaneous SCC cell lines (n ‫؍‬ 8) compared with in normal keratinocytes. SerpinA1 production by SCC cells was dependent on p38 mitogen-activated protein kinase activity and was upregulated by epidermal growth factor, tumor necrosis factor-␣, interferon-␥, and IL-1␤. Immunostaining of tissue arrays with 148 human tissue samples revealed tumor cell-associated expression of SerpinA1 in 19 of 36 actinic keratoses, 22 of 29 Bowen's disease samples, 67 of 71 sporadic SCCs, and all 12 recessive dystrophic epidermolysis bullosa-associated SCCs examined. Moreover, tumor cell-associated SerpinA1 staining was detected in all chemically induced mouse skin SCCs studied (n ‫؍‬ 17). Overexpression of SerpinA1 mRNA was also detected by quantitative RT-PCR in chemically induced mouse skin SCCs (n ‫؍‬ 14) compared with control tissues (n ‫؍‬ 14). These data identify SerpinA1 as a novel tumor cell-associated biomarker for progression of cutaneous SCCs.

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“…1 Although it is typically a straightforward diagnosis, there are many lesions, which may clinically and microscopically simulate cutaneous squamous cell carcinoma. Some of the lesions that can be the most difficult to differentiate, such as actinic keratosis and squamous cell carcinoma in situ, display varying different degrees of keratinocyte dysplasia and are typically considered neoplastic conditions.…”

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confidence: 99%

Molecular discrimination of cutaneous squamous cell carcinoma from actinic keratosis and normal skin

Hui

Binder

2011

Modern Pathology

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Actinic keratosis is widely believed to be a neoplastic lesion and a precursor to invasive squamous cell carcinoma. However, there has been some debate as to whether actinic keratosis is in fact actually squamous cell carcinoma and should be treated as such. As the clinical management and prognosis of patients is widely held to be different for each of these lesions, our goal was to identify unique gene signatures using DNA microarrays to discriminate among normal skin, actinic keratosis, and squamous cell carcinoma, and examine the molecular pathways of carcinogenesis involved in the progression from normal skin to squamous cell carcinoma. Formalin-fixed and paraffin-embedded blocks of skin: five normal skins (pooled), six actinic keratoses, and six squamous cell carcinomas were retrieved. The RNA was extracted and amplified. The labeled targets were hybridized to the Affymetrix human U133plus2.0 array and the acquisition and initial quantification of array images were performed using the GCOS (Affymetrix). The subsequent data analyses were performed using DNA-Chip Analyzer and Partek Genomic Suite 6.4. Significant differential gene expression (42 fold change, Po0.05) was seen with 382 differentially expressed genes between squamous cell carcinoma and normal skin, 423 differentially expressed genes between actinic keratosis and normal skin, and 9 differentially expressed genes between actinic keratosis and squamous cell carcinoma. The differentially expressed genes offer the possibility of using DNA microarrays as a molecular diagnostic tool to distinguish between normal skin, actinic keratosis, and squamous cell carcinoma. In addition, the differentially expressed genes and their molecular pathways could be potentially used as prognostic markers or targets for future therapeutic innovations.

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Cutaneous Squamous-Cell Carcinoma

Cited by 1,127 publications

References 81 publications

Does Notch play a tumor suppressor role across diverse squamous cell carcinomas?

Does Notch play a tumor suppressor role across diverse squamous cell carcinomas?

Serpin Peptidase Inhibitor Clade A Member 1 (SerpinA1) Is a Novel Biomarker for Progression of Cutaneous Squamous Cell Carcinoma

Molecular discrimination of cutaneous squamous cell carcinoma from actinic keratosis and normal skin

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