Form Of Nonmelanoma Skin Cancer Research Articles

Development and Optimization of Novel Emulgel Loaded with Andrographolide-Rich Extract and Sesame Oil Using Quality by Design Approach: In Silico and In Vitro Cytotoxic Evaluation against A431 Cells.

An epidermoid carcinoma is a form of non-melanoma skin cancer that originates from the outer layer of the skin's squamous cells. Previous studies have shown that andrographis extract and andrographolide inhibit the growth and proliferation of epidermoid carcinoma cells while also inducing cell cycle arrest and apoptosis. The objective of this study was to improve the anticancer efficacy of the andrographolide-rich extract by delivering it in the form of nanoemulgel. During the formulation of emulgels, sonication, and homogenization were employed, and a 22-factorial design was used to optimize the formulations through the quality by design (QbD) approach. The optimized formulation (AEE8) was subjected to preliminary evaluations along with particle size, drug release, and scanning electron microscopy (SEM) studies. The potential of the optimized emulgel against A431 cell lines was also investigated using MTT assay followed by flow cytometric analysis. The SEM results reveal that the optimized emulgel had a well-defined spherical shape, with a droplet size of 226 ± 1.8 nm, a negative surface charge of -30.1 ± 1.6 mV, and a PDI of 0.157. The cellular data indicate that AEE8 reduced the viability of the A431 cells with an IC50 of 16.56 μg/mL, as determined by MTT assay when compared to cells treated with the extract alone. Furthermore, the flow cytometric analysis of the optimized emulgel formulation demonstrated a marked G2/M phase arrest. This finding further supports the effectiveness of the gel in disrupting the cell cycle at the critical G2 and M phases, which are pivotal for cell division and proliferation. This disruption in cell cycle progression can impede the growth and spread of cancer cells, making the gel a promising candidate for anti-skin-cancer therapy. The safety of emulgels (AEE8) was validated through rigorous biocompatibility testing conducted on HDF (human dermal fibroblast) cell lines, ensuring their suitability for use. Considering the potential of the nanoemulgel, particularly AEE8, as demonstrated by its favorable properties and its ability to disrupt the cell cycle, it holds great promise as an innovative approach to treating skin cancer.

CemiplimAb-rwlc survivorship and epidemiology (CASE): A prospective study of safety and efficacy of cemiplimab in patients with advanced basal cell carcinoma in a real-world setting.

TPS9614 Background: Basal cell carcinoma (BCC) is the most common form of non-melanoma skin cancer in the United States. Surgical excision is the standard treatment, with < 1% of cases progressing to locally advanced or metastatic disease. Hedgehog pathway inhibitors (HHIs) are the first-line therapy for advanced BCC (aBCC); the US Food and Drug Administration and European Medicines Agency have approved the use of cemiplimab (a programmed cell death-1 inhibitor) in advanced BCC (aBCC) patients previously treated with (or are inappropriate for) HHI. Limited real-world data exist on the clinical characteristics, disease management and progression, and survivorship of patients with aBCC. The ongoing C.A.S.E. study aims to evaluate the efficacy, safety, disease evolution, survivorship, and patient reported outcomes (PRO) in patients treated with cemiplimab in the real-world setting. Methods: This trial in progress (NCT03836105) aims to describe the effectiveness and safety of cemiplimab 350 mg administered every 3 weeks for treatment of patients with aBCC in real-world clinical settings. Up to 100 adult patients with aBCC who are prescribed commercially available cemiplimab from ~65 study sites in the United States will be included. The duration of follow-up will be 24 months. Endpoints for this study relate to real-world efficacy, including overall survival; progression-free survival; objective response rate, (partial or complete response); and disease control rate, defined as the percentage who do not progress for ≥ 6 months; Time to response, duration of response, time to treatment failure, and disease-specific death will also be assessed. Real-world safety outcomes will also be captured, including immune-related adverse events, infusion-related reactions, and serious adverse events. Patient selection criteria and treatment patterns will be analyzed using descriptive statistics. This study also aims to describe the patient experience of real-world treatment with cemiplimab. PROs including global quality of life, functioning, and symptoms will be captured at baseline and follow-up visits via the EORTC QLQ-C30 and the Skin Care Index. Recruitment for this trial is ongoing. Clinical trial information: NCT03836105 .

Nonsurgical treatment options for basal cell carcinoma.

Basal cell carcinoma (BCC) is the most common form of nonmelanoma skin cancer. Surgery, including Mohs micrographic surgery, is considered the gold standard for the management of BCC, yet some patients may be unable to undergo surgery. This article describes effective nonsurgical options for treating superficial BCCs as well as some nodular and infiltrative BCCs.

Loss of epidermal MCPIP1 is associated with aggressive squamous cell carcinoma

BackgroundSquamous cell carcinoma (SCC) of the skin is a common form of nonmelanoma skin cancer. Monocyte chemotactic protein 1-induced protein 1 (MCPIP1), also called Regnase-1, is an RNase with anti-inflammatory properties. In normal human skin, its expression is predominantly restricted to the suprabasal epidermis. The main aim of this study was to investigate whether MCPIP1 is involved in the pathogenesis of SCC.MethodsWe analyzed the distribution of MCPIP1 in skin biopsies of patients with actinic keratoses (AKs) and SCCs. To explore the mechanisms by which MCPIP1 may modulate tumorigenesis in vivo, we established a mouse model of chemically induced carcinogenesis.ResultsSkin expression of MCPIP1 changed during the transformation of precancerous lesions into cutaneous SCC. MCPIP1 immunoreactivity was high in the thickened area of the AK epidermis but was predominantly restricted to keratin pearls in fully developed SCC lesions. Accelerated development of chemically induced skin tumors was observed in mice with loss of epidermal MCPIP1 (Mcpip1eKO). Papillomas that developed in Mcpip1eKO mouse skin were larger and characterized by elevated expression of markers typical of keratinocyte proliferation and tumor angiogenesis. This phenotype was correlated with enhanced expression of IL-6, IL-33 and transforming growth factor-beta (TGF-β). Moreover, our results demonstrated that in keratinocytes, the RNase MCPIP1 is essential for the negative regulation of genes encoding SCC antigens and matrix metallopeptidase 9.ConclusionsOverall, our results provide a mechanistic understanding of how MCPIP1 contributes to the development of epidermoid carcinoma.

Basal cell carcinoma on the conchal bowl of the ear of a young man

Basal cell carcinoma (BCC) is the most common form of nonmelanoma skin cancer. A review of the literature revealed only a few reports of BCC on the auricle or conchal bowl, usually occurring in elderly patients. Herein, we report an exceptional case of BCC in a young man with an unusual anatomical location of the tumor as a solitary erythematous to black-colored plaque located in the conchal bowl of his right ear. By thoroughly reviewing the literature, there was no other documented case of BCC located in the conchal bowl of the ear of a young adult. Dermatologists should be aware that skin tumors may also occur in uncommon anatomical locations and with unusual presentations in the young population, even if they have no known predisposing factor. Unusual presentations make clinical suspicion of skin tumors very difficult, so these lesions can easily be missed. Early diagnosis can prevent further growth, extensive destruction, and severe consequence of invasive treatments.

Retinoids in Cutaneous Squamous Cell Carcinoma.

Animal studies as early as the 1920s suggested that vitamin A deficiency leads to squamous cell metaplasia in numerous epithelial tissues including the skin. However, humans usually die from vitamin A deficiency before cancers have time to develop. A recent long-term cohort study found that high dietary vitamin A reduced the risk of cutaneous squamous cell carcinoma (cSCC). cSCC is a form of nonmelanoma skin cancer that primarily occurs from excess exposure to ultraviolet light B (UVB). These cancers are expensive to treat and can lead to metastasis and death. Oral synthetic retinoids prevent the reoccurrence of cSCC, but side effects limit their use in chemoprevention. Several proteins involved in vitamin A metabolism and signaling are altered in cSCC, which may lead to retinoid resistance. The expression of vitamin A metabolism proteins may also have prognostic value. This article reviews what is known about natural and synthetic retinoids and their metabolism in cSCC.

Evolving Role of Systemic Therapies in Non-melanoma Skin Cancer

Keratinocyte cancers – basal and cutaneous squamous cell carcinoma (BCC, cSCC) – are the most common forms of non-melanoma skin cancer (NMSC) and there has been a significant increase in their incidence globally in recent decades. Although the majority of BCC and cSCC are cured with conventional surgery or radiotherapy, certain tumour or patient-determined factors may result in these modalities being inadequate or inappropriate, for example, locally advanced or metastatic disease, high tumour multiplicity, patient comorbidities and patient preferences. In these clinical circumstances, systemic treatment may be indicated, and over the past 10 years a number of new systemic agents have been approved. Nonetheless, effective systemic therapy for keratinocyte cancers remains an area of significant unmet clinical need. Improved understanding of the molecular and immune pathogenesis underlying tumour growth and development is critical for driving future advances and is a research priority. The aim of this review is to provide clinicians with an overview of systemic treatments for BCC and cSCC and will focus on current evidence for conventional chemotherapy, targeted therapies, immunotherapy, adjuvant and neoadjuvant therapy, chemoprevention and future prospects for novel systemic treatment approaches.

128 CDC20 played an oncogenic role in human cSCC progression

Cutaneous squamous cell carcinoma (cSCC) is the second most common form of non-melanoma skin cancer, causing as many deaths yearly as melanoma in the United States. However, there are limited reliable biomarkers to predict its biological behavior and clinical outcome. The cell division cycle 20 (CDC20) has recently been reported to play a role in cancer progression. But its clinical significance in cSCC has not been studied. The aim of this study was to investigate whether CDC20 was involved in the tumorigenesis of cSCC. We firstly analyzed relative CDC20 mRNA level in two GEO microarray data using GEO2R. In GSE32628, CDC20 mRNA level is significantly higher in precancerous actinic keratoses (AK) (n=13, p=0.016) and cSCC (n=13, p=0.0007) than the paired normal skin (n=13). In GSE45216, CDC20 expression was significantly higher in well-differentiated cSCC (n=15, p=0.0205), and moderately/poorly differentiated cSCC (n=15, p=0.0003) than in AK (n=10). We then tested the CDC20 expression in 21 paired cSCC and corresponding normal tissues using immunohistochemical staining, and subsequent semiquantitative analysis of the IHC results confirmed increased CDC20 expression in cSCC tissues (n=21, p < 0.0001). Furthermore, we detected CDC20 expression in 144 samples with different pathological stage. The result showed higher CDC20 in cSCC in situ (n=27, p < 0.0001), well-differentiated cSCC (n=29, p < 0.0001), and moderately/poorly differentiated cSCC (n=25, p < 0.0001) than in normal skin (n=32) and correlated well with disease progression. CDC20 expression is very low in normal intact skin and is significantly increased in cSCC tumor cells, suggesting it can work as a biomarker for cSCC. Furthermore, elevated expression of CDC20 in both AK and cSCC in situ indicate the induction of CDC20 expression is an early event in cSCC development. However, we didn’t have any follow-up data from our patients, so we can’t draw any conclusion about the prognosis value of CDC20.

Cross-sectional associations between cutaneous viral infections and regulatory T lymphocytes in circulation.

Cutaneous viral infections and immune suppression are risk factors for some forms of nonmelanoma skin cancer; however, their interrelationship is poorly understood. To examine cross-sectional associations between cutaneous viral infections and circulating forkhead-box P3 (FOXP3)-expressing T-regulatory (Treg) cells, suppressive cells that dampen effective antitumour immunity. Blood, eyebrow hair (EBH) and skin swab (SSW) samples were collected from 352 patients 60 years and older undergoing skin screening, without prevalent skin cancer, while participating in an ongoing prospective cohort study of cutaneous viral infections and skin cancer. DNA corresponding to 98 cutaneous human papillomavirus (HPV) types and five human polyomaviruses (HPyV) was assessed in EBH and SSW. Distinct classes of circulating Treg-cell subpopulations were defined by flow cytometry including cutaneous lymphocyte antigen (CLA) and CCR4high Treg cells, both previously associated with cutaneous diseases. Age- and sex-adjusted associations between circulating T-cell populations and infection were estimated using logistic regression. Total Treg-cell proportion in peripheral blood was not associated with β HPV or HPyV infection. However, the proportion of circulating CLA+ Treg cells was inversely associated with γ HPV EBH infection [odds ratio (OR) 0·54, 95% confidence interval (CI) 0·35-0·84]. Interestingly, circulating Treg cells expressing markers indicative of antigen activation (CD27- CD45RA- FOXP3+ CD4+ ) were also inversely associated with γ HPV infection in SSW (OR 0·55, 95% CI 0·30-0·99) and EBH (OR 0·56, 95% CI 0·36-0·86). Inverse associations between circulating Treg cells and γ HPV infection suggest that localized viral infection may promote immunosuppressive cell migration into skin.

Cutaneous Squamous Cell Carcinoma: Review of the Eighth Edition of the American Joint Committee on Cancer Staging Guidelines, Prognostic Factors, and Histopathologic Variants.

Cutaneous squamous cell carcinoma is the second most common form of nonmelanoma skin cancer after basal cell carcinoma and accounts for the majority of nonmelanoma skin cancer-related deaths. In 2017, the American Joint Committee on Cancer revised the staging guidelines of cutaneous squamous cell carcinoma to reflect recent evidence concerning high-risk clinicopathologic features. This update reviews the literature on prognostic features and staging, including the eighth edition of the American Joint Committee on Cancer Staging Manual. A wide range of histopathologic variants of cutaneous squamous cell carcinoma exists, several of which are associated with aggressive behavior. A review of cutaneous squamous cell carcinoma variants, emphasizing diagnostic pitfalls, immuhistochemical findings and prognostic significance, is included. Of note, the eighth edition of the American Joint Committee on Cancer Staging Manual refers to squamous cell carcinoma of the head and neck only.

Abstract 2809: Role of c-Met in the development and progression of Tpl2-related skin cancer

Abstract Cutaneous squamous cell carcinoma (cSCC), a form of non-melanoma skin cancer, is the second most common form of cancer in the United States, with over one million cases diagnosed annually. Tpl2 (MAP3K8) is a serine threonine protein kinase in the mitogen-activated protein kinase (MAPK) signal transduction cascade. Tpl2 was identified by our laboratory as having a tumor suppressive function in skin carcinogenesis, with Tpl2 knockout mice developing significantly more papillomas and squamous cell carcinomas than matched wildtype (WT) controls. Cellular mesenchymal to epithelial transition factor (c-Met) is a receptor heightened in malignant skin cancers and involved in Tpl2 signaling. When bound to its ligand, hepatocyte growth factor (HGF), c-Met can regulate cell proliferation, survival, angiogenesis and invasion. The aim of this study was to ascertain whether c-Met signaling contributes to the heightened skin tumorigenesis in Tpl2-/- mice. Forty-four WT and Tpl2 -/- mice were subjected to a two-stage chemical carcinogenesis protocol for one year to induce skin tumors. Starting at the time of promotion, half of the WT and Tpl2 -/- mice were placed on normal diet and half received diet plus 30mg/kg Capmatinib, a pharmacological inihibitor of c-Met. This diet continued for the duration of the study. No adverse health effects were found in Capmatinib-treated mice. Similar to what we previously reported, Tpl2 -/- mice developed tumors earlier than WT controls and had statistically higher tumor incidence and overall tumor burden than WT mice. The number of tumor bearing Tpl2 -/- and Tpl2 -/- + Capmatinib fed mice was similar, although Capmatinib fed mice had a 60% reduction in overall tumor burden. Studies are underway to determine if Capmatinib affected the frequency of malignant conversion in Tpl2 -/- mice. In summary, our studies demonstrate that heightened c-Met signaling contributes to the higher tumor formation in Tpl2-/- mice and should be evaluated further as a possible therapeutic target in Tpl2-related skin cancers. Citation Format: Nicole F. Bonan, David Kowalski, Kaitlin Kudlac, Lauren G. Falkenberg, Erik Maradiaga, Kira Flaherty, Jonathan S. Wiest, Katie L. DeCicco-Skinner. Role of c-Met in the development and progression of Tpl2-related skin cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2809. doi:10.1158/1538-7445.AM2017-2809

An image of cutaneous squamous cell carcinoma derived from complex epidermoid cyst in a 65-year-old male

An epidermal cyst is a benign intradermal lesion and may occur anywhere in the body. Carcinoma arising in a preexisting epidermal cyst is uncommon. Cutaneous squamous cell carcinoma is the second most common form of nonmelanoma skin cancer. A 65-year-old male with light skin pigmentation presented with chronic lower back pain secondary to a large “cauliflower-like” mass over his left flank, which started out as a “cheesy tumor” 20 years ago. The patient reported that the mass had recently begun to drain foul-smelling mucous and bloody discharge and was growing in size. This image illustrates the importance of proper comprehensive biannually or annually history and physical examination as screening tools for skin cancer. Primary care physicians are encouraged to educate their patients on the use of sunscreen containing zinc oxide and conducting regular self-examinations. The following core competencies are addressed in this article: Medical knowledge, Patient care.

CONSENSUS REPORT: Recognizing non‐melanoma skin cancer, including actinic keratosis, as an occupational disease – A Call to Action

1. Non-melanoma skin cancer (NMSC) is by far the most common cancer diagnosed in westernized countries, and one of the few almost preventable cancers if detected and treated early as up to 90% of NMSC may be attributed to excessive exposure to ultraviolet radiation. 2. The incidence of NMSC is increasing: 2-3 million people are diagnosed worldwide annually, with an average yearly increase of 3-8% among white populations in Australia, Europe, the US and Canada over the last 30 years. 3. The link between solar ultraviolet (UV) radiation and certain forms of NMSC is clearly recognized. It is estimated that outdoor workers are exposed to an UV radiation dose 2-3 times higher than indoor workers, and there is a growing body of research linking UV radiation exposure in outdoor workers to NMSC: I. Occupationally UV-exposed workers are at least at a 43% higher risk of basal cell carcinoma (BCC) and almost doubled risk of squamous cell carcinoma (SCC) compared to the average population, with risk increasing with decreasing latitude. II. The risk for BCC, SCC and actinic keratosis (AK) among workers who have worked outdoors for more than 5 years is 3-fold higher than the risk among those with no years of working outdoors. 4. Primary prevention, early detection, treatment and regular follow-up of skin cancer (NMSC and melanoma) are shown to be beneficial from a health economic perspective. 5. Action is needed at international, European and national level to legislate for recognizing AK and NMSC as an occupational disease, which has the potential to improve access to compensation and drive preventative activities. 6. This report is a Call to Action for: I. The engagement of key stakeholders, including supranational institutions, national governments, trade organizations, employers, workers and patient organizations to drive change in prevention and protection of at-risk groups. II. Employers should be obliged to prevent outdoor worker's UV exposure from exceeding limit values, and to implement occupational skin cancer screening programmes among the at-risk workforce. III. Educational programmes for the outdoor workforce are needed to improve health literacy and drive behavioural change. IV. Nationally, steps to improve notifications and surveillance of skin cancers through both occupational services and public health programmes are required. V. Future research activities should focus on the precise definition of at-risk groups among outdoor workers through increased data gathering, including UV-dosimetry, and evaluation.

Abstract B47: Curcumin C3 ® prevents ultraviolet B radiation-induced epidermal damage in JB6 cells and mouse skin via a Fibroblast growth factor-2-dependent manner

Abstract Background and Significance: Non-melanoma skin cancer (NMSC) is the most common skin cancer in the U.S., with over a million new cases anticipated annually. Cutaneous squamous cell carcinoma (SCC) is a more aggressive form of NMSC. Chronic exposure to solar ultraviolet (UVB) is the major etiologic factor causing skin cell damage, photoaging and malignant transformation leading to SCC. UVB is a carcinogen and our previous studies established oral administration of Curcumin C3 complex (C3), a natural occurring polyphenol compound mixture, delayed UVB-induced tumor onset and multiplicity, but not tumor progression. Accordingly, we sort to determine the preventative efficacy of C3® against UVB-induced photodamage using JB6 cells and SKH-1 hairless mouse epidermis on the earlier neoplastic events in the development of UVB-induced skin carcinogenesis. Methods: SKH-1 mice were either administered vehicle or C3 (100mg/kg/b.w) complex orally for 14 days followed by a single exposure to UVB radiation (180mj/cm2). Mice were euthanized 24 hours after UVB exposure and skin tissues and serum were collected. For in vitro studies, promoter–sensitive JB6 mouse epithelial cells were pre-treated with C3® for 2 h and the effects on UV-induced early molecular events were assessed. Results: C3® attenuated UVB-induced epidermal hyperplasia and significantly decreased epidermal and plasma levels of fibroblast growth factor-2 (FGF-2); an important mitogen implicated in proliferation and differentiation of skin keratinocytes. Interestingly, the effects of C3® complex on FGF-2 levels were accompanied with a significant reduction in UVB-induced Nuclear factor KappaB (NF-KB) activation; an important nuclear transcription factor for tumor promotion. Further, the decrease in NF-KB was associated with an inhibition of BCL2 expression to induce apoptosis. In vitro, pretreatment of JB6 cells with C3® significantly decreased UVB-induced proliferation with a corresponding decrease in FGF-2 mRNA and protein levels. Further, C3 complex inhibited NF-KB phosphorylation and increased Bax expression leading to cell apoptosis. Conclusion: Our findings underscore the importance of curcumin (C3) in preventing UVB-induced skin cancer. It provides new insight into curcumin's role through FGF-2 in modulating the pathogenesis of photo carcinogenesis. Citation Format: Alok R. Khandelwal, Arun Anandharaj, Oleksandr Ekshyyan, Lauren D. Saucier, Tara N. Moore-Medlin, Fleurette Abreo, Cherie-Ann O. Nathan. Curcumin C3 ® prevents ultraviolet B radiation-induced epidermal damage in JB6 cells and mouse skin via a Fibroblast growth factor-2-dependent manner. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr B47.

MicroRNA profiling for early detection of nonmelanoma skin cancer.

microRNAs (miRNAs) are single-stranded, noncoding RNA molecules. Given the vast regulatory potential of miRNAs and their often tissue-specific and disease-specific expression patterns, miRNAs are being assessed as possible biomarkers to aid diagnosis and prediction of different types and stages of cancers, including skin cancer. Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most common forms of nonmelanoma skin cancer (NMSC). BCC originates from the basal layer of the epidermis, while SCC arises from epidermal keratinocytes or from the dermal appendages. Although NMSCs are currently the most common types of malignancies, both BCC and SCC have a better than 95% cure rate if detected early. To identify plasma miRNAs suitable for early detection of NMSC. Expression profiles of 741 miRNAs were evaluated using high-throughput real-time quantitative PCR from plasma samples in 42 patients with NMSC and 282 healthy controls (HCs). Our results demonstrated that in patients with NMSC, compared with HCs,expression levels of miR-30e-3p, miR-145-5p, miR-186-5p and miR-875-5p were significantly (P<0.05) upregulated, while those of miR-19a-3p, miR-25-3p, miR-30a-5p, miR-451 and miR-576-3p were significantly downregulated. Our study suggests that the miRNAs with significant changes in expression (miR-19a-3p, miR-25-3p, miR-30a-5p, miR-145-5p and miR-186-5p) could serve as novel noninvasive biomarkers for detection ofNMSC.

Non-melanoma Skin Cancer in Canada Chapter 5: Management of Squamous Cell Carcinoma.

Squamous cell carcinoma (SCC) is the second-most common form of non-melanoma skin cancer (NMSC). To provide guidance to Canadian health care practitioners regarding management of SCCs. Literature searches and development of graded recommendations were carried out as discussed in the accompanying introduction (chapter 1 of the NMSC guidelines). SCCs are sometimes confined to the epidermis, but they can also invade nearby tissues and, in some cases, metastasize to neighbouring lymph nodes or other organs. This chapter discusses the natural history, staging, prognosis, and management of SCC--a tumour type that is less common but typically more aggressive than BCC. For this reason, margin control is strongly preferred in treating SCCs. Although approaches such as cryosurgery and radiation therapy may be considered for some patients, surgical excision--sometimes coupled with radiation--remains the cornerstone of SCC management. Patients with high-risk SCC may also be considered for referral to an appropriate multidisciplinary clinic.

Frequency and features ofTP53mutation in 30 Chinese patients with sporadic basal cell carcinoma

Basal cell carcinoma (BCC) is a prevalent form of nonmelanoma skin cancer. Although numerous studies in white populations suggest that mutations in the TP53 gene play an important role in the development of BCC, it is not clear whether this is also the case in East Asian populations such as in China. To investigate the frequency and the features of TP53 mutation in sporadic BCC in a Chinese population. In total, 30 patients with sporadic BCC, who had previously taken part in a study on PTCH1 mutations, were enrolled. BCC and control cells were obtained by laser-capture microdissection, and DNA was amplified and sequenced for analysis of TP53 mutations. In the 30 BCC samples, 6 TP53 point mutations were found (frequency of 20%), and 4 of these 6 mutations had ultraviolet (UV)-specific alterations. Combining these results with those of the previous study on PTCH1 mutations, we found that two patients with had three types of genetic alterations (each had two PTCH1 mutations and one TP53 point mutation). A further two patients each had one PTCH1 mutation and one UV signature TP53 mutation. In addition, the total number of UV-specific mutations of PTCH1 and TP53 accounted for 20% of the total patient group. The incidence of TP53 mutation in BCC in our Chinese subjects was lower than that reported for white populations. Many of the patients carried mutations of other genes in addition to of TP53. The majority of TP53 mutations were UV-induced specific alterations. However, the results of the two studies on TP53 and PTCH1 indicated that the incidence of UV-specific mutations is much lower in Chinese than in white populations.

Medical approaches to non-melanoma skin cancer

Medical therapy represents an alternative treatment approach that can be considered for some forms of non-melanoma skin cancer (NMSC). In selected cases, topical treatments are preferable to invasive procedures, especially in the case of multifocal lesions, unclear lesion edges, risk of keloids, surgical risk factors and localization in some areas such as the face and décolletage, as the cosmetic outcomes are generally excellent. In the case of advanced and metastatic NMSC, molecularly targeted therapy represents a reasonably promising alternative to classical cytotoxic chemotherapy. Based on the existing literature and the authors’ experience, this paper analyzes and discusses the mechanisms of action, formulations, official and off-label indications, efficacy, side effects and contraindications of medical treatments that are utilized in the treatment of NMSC, including 5-fluorouracil, imiquimod, diclofenac, ingenol mebutate, resiquimod, piroxicam, dobesilate, betulinic acid, vismodegib, cetuximab, gefitinib and cytotoxic chemotherapy.

Radiotherapy for Metastatic Merkel Cell Carcinoma: A Review of the Literature

Introduction. Merkel cell carcinoma is a rare form of non-melanoma skin cancer of neuroendocrine origin. Optimal management of patients is controversial and the role of radiotherapy is unclear. Purpose. The purpose of this study was to review the efficacy of RT in the treatment of both local and distant metastatic disease from MCC. Methods. A literature search was conducted in MEDLINE (1946—January Week 1 2012) and Embase (1980–2012 Week 2). Articles of interest analyze the efficacy of radiotherapy for treatment of metastatic MCC and did not exclude case reports. Results. All articles except one focusing on the role of radiotherapy were of retrospective origin or case series. Significant limitations applied in all studies due to limited sample sizes and the retrospective nature of these studies. Radiotherapy improves locoregional control in the adjuvant setting, and many series suggest an improvement in overall survival. In cases where surgery is not possible, definitive radiotherapy may be an as-efficacious alternative. The radiosensitive nature of MCC coupled with existing reports suggests that treatment via current protocols for other primary tumors is adequate. Conclusion. Further studies should be conducted prospectively to clarify the true role of radiotherapy in metastatic MCC.

Metastatic cutaneous squamous cell carcinoma shows frequent deletion in the protein tyrosine phosphatase receptor Type D gene

Cutaneous squamous cell carcinoma (cSCC) is the second most common form of nonmelanoma skin cancer (NMSC), and its incidence is increasing rapidly. Metastatic cSCC accounts for the majority of deaths associated with NMSC, but the genetic basis for cSCC progression remains poorly understood. A previous study identified small deletions (typically <1 Mb) in the protein tyrosine phosphatase receptor Type D (PTPRD) gene that segregated with more aggressive cSCC. To investigate the apparent association between deletion within PTPRD and cSCC metastasis, a series of 74 formalin-fixed paraffin-embedded tumors from 31 patients was analyzed using a custom Illumina 384 SNP microarray. Deletions were found in 37% of patients with metastatic cSCC and were strongly associated with metastatic tumors when compared to those that had not metastasized (p = 0.007). Subsequent mutation analysis revealed a higher mutation rate for PTPRD than has been reported in any other cancer type, with 37% of tumors harboring a somatic mutation. Conversely, bisulfite sequencing showed that methylation was not a mechanism of PTPRD disruption in cSCC. This is the first report to observe an association between deletion within PTPRD and metastatic disease and highlights the potential use of these deletions as a diagnostic biomarker for tumor progression. Combined with the high mutation rate observed in our study, PTPRD is one of the most commonly altered genes in cSCC and warrants further investigation to determine its significance for metastasis in other tumor types.