From keratinocyte to cancer: the pathogenesis and modeling of cutaneous squamous cell carcinoma

Tumor-associated tissue eosinophilia was first described in 1896 in cervical carcinoma and is defined as eosinophilic infiltration in a tumor that is not associated with necrosis or ulceration. Its functional role remains unclear [1]. Eosinophilic infiltration has been reported in carcinomas located in the oral cavity, larynx, pharynx, gastrointestinal tract, lungs, cervix, and external genitalia; however, the literature includes limited data on eosinophilic infiltration in cutaneous squamous cell carcinoma (SCC) [1,2].Objectives. The literature does not include any comparative study on the eosinophil count in premalignant and malignant cutaneous squamous neoplasias. Our aim was to compare the tissue eosinophilic count in actinic keratosis (AK) and cutaneous squamous cell carcinoma (SCC). Methods. The study included 20 AK and 20 invasive SCC patients. Age, gender, and lesion location were retrospectively evaluated as clinical parameters. Histopathological parameters included density of inflammation score, lesion grade, and the lesion-associated eosinophil count per 10 high-power (40×) microscopic fields, all of which were compared between groups. Results. In all, 65% of the AK group had lesions with moderate inflammation, whereas 85% of the SCC group had lesions with dense inflammation (p=0.001). The mean eosinophil count in the SCC group was significantly higher than that in the AK group, independent of the density of inflammation (p=0.000). In addition, lesion grade was not associated with the eosinophil count in either group (AK group: p=0.601; SCC group: p=0.416). Conclusions. Cutaneous SCC lesions had higher eosinophil counts than AK lesions, indicating the role of the eosinophil count as a histopathological marker of stromal invasion.

show abstract

“…Additionally, the mean eosinophil count 10 HPFs-1 in AK-II/AK-III and SCC lesions differed significantly (2.18±1.8 vs. 45±26. 3…”

Section: Resultsmentioning

confidence: 99%

Tissue eosinophilia: a histopathological marker associated with stromal invasion but not histopathological grade in cutaneous squamous neoplasia

2015

View full text Add to dashboard Cite

show abstract

“…Cutaneous carcinomas originate from epidermal stem cells that have the potential for self‐renewal and multi‐lineage differentiation; these cells are located in the hair follicle bulge and the basal layer of the interfollicular epidermis 8. Depending on the study, cutaneous carcinomas account, for approximately 15–50% of all cutaneous tumors in cats, making it among the 4 most common skin tumors in cats 2, 3.…”

mentioning

confidence: 99%

Electroporation Enhances Bleomycin Efficacy in Cats with Periocular Carcinoma and Advanced Squamous Cell Carcinoma of the Head

Spugnini¹,

Pizzuto²,

Filipponi

et al. 2015

Veterinary Internal Medicne

View full text Add to dashboard Cite

BackgroundAdvanced carcinoma of the head represents a substantial health problem in cats for local control and overall survival.ObjectivesEvaluate the capability of electrochemotherapy (ECT) to improve bleomycin efficacy in cats with periocular carcinoma and advanced carcinoma of the head.AnimalsTwenty‐one cats with periocular carcinoma (17 squamous cell carcinoma [SCC] and 4 anaplastic carcinoma) and 26 cats with advanced SCC of the head.MethodsNonrandomized prospective controlled study. Periocular carcinoma cohorts: 12 cats were treated with bleomycin (15 mg/m2 IV) coupled with ECT under anesthesia; 9 cats were treated with bleomycin alone. Advanced head SCC cohorts: 14 cats were treated with bleomycin (15 mg/m2 IV) coupled with ECT administered under sedation; 12 control cats were treated with bleomycin alone. ECT treatments (2–8) were performed every other week until complete remission (CR) or tumor progression occurred.ResultsToxicities were minimal and mostly treated symptomatically. Overall response rate in the ECT treated animals was 89% (21 Complete Response [CR] and 2 Partial Response [PR]) whereas controls had response rate of 33% (4 CR and 3 PR). Median time to progression in ECT group was 30.5 months, whereas in controls it was 3.9 months (P < .0001). Median time to progression for ECT cohorts was 24.2 months for periocular cohort and 20.6 in advanced head SCC cohort, respectively.ConclusionsElectrochemotherapy is well tolerated for advanced SCC of the head in cats; its use may be considered among loco‐regional strategies for cancer therapy in sensitive body regions such as periocular region.

show abstract

“…[1][2][3] Both tumors are strongly associated with chronic ultraviolet (UV) radiation exposure and occur primarily, but not exclusively, on sun-exposed areas of the body. [4][5][6][7][8] The most commonly mutated gene in basal cell carcinoma and squamous cell carcinoma is TP53, with the majority of mutations consistent with UV as the mutagen. 9,10 Inactivating mutations in the PTCH gene, the gene responsible for nevoid basal cell carcinoma syndrome, have also been identified in sporadic basal cell carcinoma, also with evidence for UV causation.…”

mentioning

confidence: 99%

Mutations of the TERT promoter are common in basal cell carcinoma and squamous cell carcinoma

2014

View full text Add to dashboard Cite

Telomerase is frequently expressed in cancer and contributes to carcinogenesis. Two recent publications report the identification of a set of recurrent mutations in melanoma in the promoter of the telomerase reverse transcriptase gene (TERT) that appears to be the result of mutagenesis from ultraviolet (UV) radiation. Both groups reported that the mutations increase the transcription of TERT. This prompted our search for similar mutations in two other UV-related skin cancers, basal cell carcinoma, and squamous cell carcinoma. We found that the activating TERT promoter mutations reported in melanoma are also frequent in squamous cell carcinoma (50%) and basal cell carcinoma, the latter including both sporadic tumors (78%) and tumors from patients with nevoid basal cell carcinoma syndrome (68%). These mutations were found in only 1 of 11 Bowen's disease (squamous cell carcinoma in situ) specimens, and in none of 15 non-malignant skin specimens and 57 blood specimens. The mutations were frequently homozygous or hemizygous, with little or no normal signal at the mutated positions. These data suggest that TERT promoter mutations are the most frequent putative oncogenic mutations in cutaneous cancer.

show abstract

From keratinocyte to cancer: the pathogenesis and modeling of cutaneous squamous cell carcinoma

Cited by 461 publications

References 106 publications

Tissue eosinophilia: a histopathological marker associated with stromal invasion but not histopathological grade in cutaneous squamous neoplasia

Tissue eosinophilia: a histopathological marker associated with stromal invasion but not histopathological grade in cutaneous squamous neoplasia

Electroporation Enhances Bleomycin Efficacy in Cats with Periocular Carcinoma and Advanced Squamous Cell Carcinoma of the Head

Mutations of the TERT promoter are common in basal cell carcinoma and squamous cell carcinoma

Contact Info

Product

Resources

About