Types Of Nonmelanoma Skin Cancer Research Articles

Prevalence of a History of Skin Cancer in 2007

To estimate the 2007 person prevalence of common types of nonmelanoma skin cancer (NMSC), basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), or both, in the United States using an incidence-based mathematical model; and to compare the prevalence of skin cancer with that of other common cancers. I developed a mathematical model to estimate the prevalence of NMSC in the United States in 2007. This model used age-specific incidence data adjusted to reflect changes in incidence from 1957 to 2006, the age distribution of the population from 1957 to 2006, and the likelihood that an incident tumor was the first ever for that person. I performed sensitivity analyses that varied my assumption about change in incidence over time and proportion of incident tumors that were a first-ever NMSC for an individual. I used standard methods for analysis of survey data to calculate the number of persons who report a history of the selected cancers and published Surveillance, Epidemiology, and End Results (SEER) estimates for incidence-based estimates for prevalence of cancers other than NMSC. National Health Interview Survey (NHIS) 2007 data, National Cancer Institute Skin Cancer Incidence data (1977-1978), and SEER data. Main Outcome Measure Incidence-based estimate of prevalence of NMSC and melanoma and patient reports of a history of skin and selected other cancers. Approximately 13 million white non-Hispanics living in the United States at the beginning of 2007 have had at least 1 NMSC. About 1 in 5 seventy-year-olds have had NMSCs, and most of those affected have had multiple NMSCs. In the 2007 NHIS estimates, only 5 million persons report a history of skin cancer, less than half the number estimated based on incidence and survival data. My incidence-based model indicates that the prevalence of a skin cancer history is about 5 times higher than that of breast or prostate cancer and greater than the 31-year prevalence of all other cancers combined. Despite their high frequency, population-based incidence and burden data for BSC and SCC are largely lacking.

Viral-Associated Nonmelanoma Skin Cancers: A Review

Nonmelanoma skin cancers are the most common malignancies in the United States, with over 1.3 million patients diagnosed yearly. Several types of nonmelanoma skin cancer and precancerous lesions have an associated viral pathogenesis, including epidermodysplasia verruciformis, verrucous carcinoma, bowenoid papulosis, Kaposi sarcoma, squamous cell carcinoma, and, most recently, Merkel cell carcinoma. It is now widely accepted that high-risk human papillomaviruses (HPVs) play a key role in pathogenesis of cervical and anogenital cancer. Currently, 108 types of HPV have been discovered. They can be divided into genera including alpha, beta, and gamma HPVs, which comprise the majority of cutaneous HPVs. The relationship between viruses and cancer is a popular focus of research in an era of AIDS and organ transplantation, where immunosuppression is not uncommon. The incidence of viral-related malignancies in these populations is increasing. Because of the widespread nature of these cutaneous malignancies, an evaluation of these conditions is valuable. This review of the literature will focus on the histologic aspects of viral-associated skin malignancies, as well as the epidemiology, etiology, and clinical aspects of these diseases.

Transcriptional profiling identifies an interferon‐associated host immune response in invasive squamous cell carcinoma of the skin

Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) represent the 2 most common types of nonmelanoma skin cancer. Both derive from keratinocytes but show a distinct biological behavior. Here we present transcriptional profiling data of a large cohort of tumor patients (SCC, n = 42; BCC, n = 114). Differentially expressed genes reflect known features of SCC and BCC including the typical cytokeratin pattern as well as upregulation of characteristic cell proliferation genes. Additionally, we found increased expression of interferon (IFN)-regulated genes (including IFI27, IFI30, Mx1, IRF1 and CXCL9) in SCC, and to a lower extent in BCC. The expression of IFN-regulated genes correlated with the extent of the lesional immune-cell infiltrate. Immunohistological examinations confirmed the expression of IFN-regulated genes in association with a CXCR3+ cytotoxic inflammatory infiltrate on the protein level. Of note, a small subset of SCC samples with low expression of IFN-regulated genes included most organ transplant recipients receiving immunosuppressive medication. Collectively, our findings support the concept that IFN-associated host responses play an important role in tumor immunosurveillance in the skin.

Ultraviolet responses of Gorlin syndrome primary skin cells

Gorlin syndrome, or naevoid basal cell carcinoma syndrome (NBCCS), is an autosomal dominant disorder associated with mutations in the PTCH1 gene, which encodes the receptor of SONIC HEDGEHOG. In addition to developmental abnormalities, patients with NBCCS are prone to basal cell carcinoma (BCC), the most frequent type of nonmelanoma skin cancer in humans. As ultraviolet (UV) exposure plays a prominent role in the development of sporadic BCC, we aimed to determine whether primary NBCCS skin cells exhibit differential responses to UV exposure compared with wild-type (WT) skin cells. Primary fibroblast and keratinocyte strains were isolated from nonlesional skin biopsies of 10 patients with characteristic NBCCS traits. After identification of PTCH1 mutations, capacities of NBCCS cells to repair UV-induced DNA lesions and to survive after UV irradiation, as well as p53 responses, were compared with those of WT skin cells. The c1763insG PTCH1 mutation is described for the first time. DNA repair and cell survival analyses following UV irradiation revealed no obvious differences between responses of NBCCS and WT fibroblasts and keratinocytes. However, p53 accumulation after UV irradiation was abnormally persistent in all NBCCS primary keratinocyte strains compared with WT keratinocytes. Our observations that NBCCS cells harbour normal DNA repair and survival capacities following UV irradiation better explain that BCC proneness of patients with NBCCS does not solely concern body areas exposed to sunlight and suggest rather that it might be due to cell cycle alterations.

Spontaneous Squamous Cell Carcinoma Induced by the Somatic Inactivation of Retinoblastoma and Trp53 Tumor Suppressors

Squamous cell carcinomas (SCC) represent the most aggressive type of nonmelanoma skin cancer. Although little is known about the causal alterations of SCCs, in organ-transplanted patients the E7 and E6 oncogenes of human papillomavirus, targeting the p53- and pRb-dependent pathways, have been widely involved. Here, we report the functional consequences of the simultaneous elimination of Trp53 and retinoblastoma (Rb) genes in epidermis using Cre-loxP system. Loss of p53, but not pRb, produces spontaneous tumor development, indicating that p53 is the predominant tumor suppressor acting in mouse epidermis. Although the simultaneous inactivation of pRb and p53 does not aggravate the phenotype observed in Rb-deficient epidermis in terms of proliferation and/or differentiation, spontaneous SCC development is severely accelerated in doubly deficient mice. The tumors are aggressive and undifferentiated and display a hair follicle origin. Detailed analysis indicates that the acceleration is mediated by premature activation of the epidermal growth factor receptor/Akt pathway, resulting in increased proliferation in normal and dysplastic hair follicles and augmented tumor angiogenesis. The molecular characteristics of this model provide valuable tools to understand epidermal tumor formation and may ultimately contribute to the development of therapies for the treatment of aggressive squamous cancer.

Significance of eIF4E expression in skin squamous cell carcinoma

Cutaneous squamous cell carcinoma (SCC) is a malignant tumour of keratinising epidermal cells. This type of skin cancer is the second leading cause of death after melanoma, and it is the second most common type of non-melanoma skin cancer after basal cell carcinoma. The cellular and molecular events involved in the progression of skin cancers are largely unknown. Increased protein synthesis is necessary for the transition of cells from quiescence to proliferation. Translational control is critical for the proper regulation of the cell cycle, tissue induction and growth. Eukaryotic initiation factor eIF4E, an important regulator of translation, plays critical roles in neo-plastic transformation and cancer progression. We investigated eIF4E expression in 49 skin samples (six normal tissues, eight Bowen diseases, seven stage I, 10 stage II, 13 stage III and five stage IV SCCs). Results obtained demonstrated that all SCC samples, evaluated by SDS-PAGE, Western blotting and cap-affinity chromatography using m7GTP-sepharose, presented eIF4E expression (13.6+/-1.2), whereas, starting from stage 0 (4.1+/-0.9) to stage I (7.4+/-1.4), stage II (12.1+/-2.4), stage III (18.1+/-3.0) and stage IV (26.2+/-3.8) SCCs, a constant and significant increase of protein over expression (P<0.001) was observed. A high expression of eIF4E is correlated with advanced stages. The results presented in this study demonstrate a possible role of eIF4E in SCC.

Elevated 8-Isoprostane Levels in Basal Cell Carcinoma and in Uva Irradiated Skin

Isoprostanes are prostaglandin isomers produced from the peroxidation of polyunsaturated fatty acids from the cellular membrane. They have been used as a specific index of cellular lipoperoxidation and as an indirect measure of oxidative stress. However, these molecules also present several biological activities. An oxidative environment measured as the presence of other indirect measurements of reactive oxygen species lipoperoxidation has recently been described in basal cell carcinoma, the most frequent type of non-melanoma skin cancer. This study aims to measure the levels of 8-isoprostaglandin F2alpha, an isoprostane widely studied in other models as a by-product of ROS-induced lipid peroxidation, in basal cell carcinoma and in UVA irradiated healthy skin. We found that 8-iso-PGF2 alpha is present in higher levels in BCC specimens compared to healthy non sun-exposed skin, confirming previous studies on the production of lipoperoxidation in this tumor. Moreover, we demonstrated that topical pre-treatment with a compound containing vitamin E is capable of reducing 8-iso-PGF2 alpha formation in UV irradiated skin suggesting a role for isoprostanes in UV induced inflammation and eventually carcinogenesis and confirming the function of vitamin E as an antioxidant in this model.

Anti-Rejection Drug Treatment Increases Basal Cell Carcinoma Burden in Ptch1+/- Mice

The development of extensive and severe non-melanoma skin cancer is an extremely common complication of organ transplantation and is assumed to be caused by long-term treatment with anti-rejection drugs (ARD). Despite this florid clinical problem, ARD treatments have been reported to affect experimental murine skin carcinogenesis only weakly. We report here that treatment of cesium-137-irradiated Ptch1+/- mice with immunosuppressive doses of cyclosporine A plus prednisolone for 4-1/2 mo increased basal cell carcinoma burden by 2.5-fold. Thus, these mice provide a good model for study of the effects of long-term administration of ARD on at least one type of non-melanoma skin cancer.

Keratinocyte carcinoma.

Keratinocyte carcinoma is by far the most common cancer in the United States. Basal cell carcinomas and squamous cell carcinomas account for approximately 80% and 20% of cases of KC, respectively. The term nonmelanoma skin cancer is commonly used to refer to squamous cell carcinomas and basal cell carcinomas; however, other types of nonmelanoma skin cancer, such as adnexal tumors and sarcomas, are less common and differ in their cell type, behavior, and epidemiologic features from KC. Primary care clinicians are well positioned to diagnose KC and to educate patients about preventive measures such as sun protection and self-examination. Here we review epidemiologic data and strategies for prevention, diagnosis, and clinical management of KC.

The Influence of Painful Sunburns and Lifetime Sun Exposure on the Risk of Actinic Keratoses, Seborrheic Warts, Melanocytic Nevi, Atypical Nevi, and Skin Cancer

Painful sunburns are implicated in the pathogenesis of squamous cell carcinoma, basal cell carcinoma, and malignant melanoma. Chronic exposure to ultraviolet radiation is known as the most important risk factor for the development of actinic keratoses and squamous cell carcinoma. The purpose of the study was to assess the effect of painful sunburns and lifetime sun exposure on the development of actinic keratoses and seborrheic warts in relation to the development of squamous cell carcinoma and basal cell carcinoma, and on the development of melanocytic nevi and atypical nevi in relation to the development of malignant melanoma. We made use of a cohort of 966 individuals who participated in a case-control study to investigate environmental and genetic risk factors for skin cancer. Exposure measurements for sunlight were collected and actinic keratoses, seborrheic warts, melanocytic nevi, and atypical nevi were counted. Relative risks were estimated using exposure odds ratios from cross-tabulation. Multivariate logistic regression was used to adjust for potential confounders. The recall of painful sunburns before the age of 20 y was associated with an increased risk of squamous cell carcinoma, nodular basal cell carcinoma, and multifocal superficial basal cell carcinoma as well as actinic keratoses. Odds ratios with 95% confidence intervals adjusted for age, sex, and skin type were 1.5 (0.97; 2.3); 1.6 (1.1; 2.2); 2.6 (1.7; 3.8); and 1.9 (1.4; 2.6) for the three types of nonmelanoma skin cancer and actinic keratoses, respectively. Painful sunburns before the age of 20 y were also associated with an increased risk of malignant melanoma and the development of its precursors, melanocytic nevi and atypical nevi. Odds ratios with 95% confidence intervals adjusted for age, sex, and skin type were 1.4 (0.86; 2.1); 1.5 (1.1; 2.0); and 1.4 (0.88; 2.3) for malignant melanoma and the two types of precursors, respectively. Lifetime sun exposure was predominantly associated with an increased risk of squamous cell carcinoma (p-value for trend=0.03) and actinic keratoses (p-value for trend <0.0001) and to a lesser degree with the two types of basal cell carcinoma. By contrast, lifetime sun exposure appeared to be associated with a lower risk of malignant melanoma, despite the fact that lifetime sun exposure did not diminish the number of melanocytic nevi or atypical nevi. Neither painful sunburns nor lifetime sun exposure were associated with an increased risk of seborrheic warts.

P53 Patches are Not Increased in Patients with Multiple Nonmelanoma Skin Cancers

p53 Patches are Not Increased in Patients with Multiple Nonmelanoma Skin Cancers

Mohs micrographic surgery referral patterns: the University of Missouri experience.

Mohs micrographic surgery (MMS) provides a higher cure rate for nonmelanoma skin cancer (NMSC) than other forms of therapy. The American Academy of Dermatology has published recommended guidelines for MMS referral. However, factors other than the location, size, and type of NMSC may often affect the referral process. To tabulate and analyze the rates of referral of NMSC for MMS by the dermatology clinics within the University of Missouri system. Data obtained for every biopsy-proven basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) diagnosed at each of our four dermatology clinics during the 3-year period of October 1993-September 1996 were cross-referenced with our Mohs surgery clinic logbook to identify which patients had been referred for MMS. During the study period, 19.2% of NMSC patients diagnosed were referred for MMS. However, there was significant disparity in referral rates among our four clinics. When the skewed data from our Veterans Administration Hospital clinic were discounted, the overall referral rate from the other clinics was found to be 30.8%. Our finding of a 30.8% referral rate of NMSC for MMS (27. 4% for SCC and 32.9% for BCC) within our university dermatology system is similar to the rates found in previous studies by the Mayo Clinic and Brooke Army Medical Center. MMS referral patterns are affected by many factors besides whether the NMSC meets MMS criteria, including the preference of each individual referring physician, patient, and involved insurance carrier.

Skin tumors in photochemotherapy for psoriasis: a single-center follow-up of 496 patients.

The significance of oral psoralen photochemotherapy (PUVA) for the development of nonmelanoma skin cancers (NMSC) is still controversial. We evaluated 496 psoriatics, who received PUVA treatment according to the European PUVA protocol in order to reassess the influence of the cumulative UVA dose on the development of NMSC and to answer the question if there is a UVA threshold dose above which the carcinogenic risk is increased. The study was conducted as a retrospective investigation. All patients were seen personally. Age, sex, skin type, cumulative UVA dose and carcinogenic risk factors (arsenic, X-rays, tar, UVB, methotrexate) were recorded and investigated by marginal (MA) and partial effects analyses (PA) according to the Cox regression model. In 14 patients (2.8%), one or multiple histologically confirmed NMSC were diagnosed. Nine patients (1.8%) had squamous cell carcinoma (SCC), 5 patients (1.0%) had basal cell carcinoma (BCC). No patient had both types of NMSC. None of the SCC had metastasized. By taking the appearance of BCC and SCC as the endpoint, arsenic [MA: relative risk (RR) = 7.62; PA:RR = 5.36], tar (MA:RR = 4.51; PA:RR = 3.83) and methotrexate (MTX; MA:RR = 4.97; PA:RR = 4.07) appear to produce strong and significant effects (p < 0.05), both in MA and PA. Using the endpoint SCC only, the effect of the natural logarithm of UVA (ln UVA; RR = 2.47), arsenic (RR = 11.2), tar (RR = 9.92) and MTX (RR = 7.1) is significant (p < 0.05) in MA. In PA, only the effect of arsenic (RR = 5.19) is strong and significant (p < 0.05) while the effects of tar (RR = 7.85), MTX (RR = 3.22) and ln UVA (RR = 2.77) are strong but of borderline significance (p = 0.05-0.11). Nonlinear effects of ln UVA on the risk of SCC were far from significant (p > 0.2). PUVA with the European treatment protocol appears to be only a weak carcinogen by itself for SCC with a linear increase in tumor risk but not for BCC development.

The Expression and Localization of bcl-2 Protein in Normal Skin and in Non-Melanoma Skin Cancers

Non-melanoma skin cancers are the most commonly diagnosed malignancies and are typically indolent in their clinical behavior. Although predisposing factors leading to the development of these cancers, such as ultraviolet irradiation, are well described, the molecular events involved in their pathogenesis are incompletely understood. The localization of bcl-2 expression within the skin was determined using immunohistochemical methodologies and an anti-bcl-2 monoclonal antibody. The cytoarchitectural distribution of bcl-2 protein in normal skin included basal keratinocytes, the dermal papillae of the hair follicle, the keratinized Huxley's and Henle's layers, and the keratinized outer root sheath cells of the isthmus and infundibulum of the hair follicle. In addition, intense immunoreactivity was noted in the secretory coil of eccrine sweat glands. The distribution of bcl-2 protein within normal skin did not correlate with the known histologic localization of stem cell compartments. Basal cell carcinomas expressed high levels of bcl-2 protein. In contrast, squamous cell carcinomas typically exhibited no immunohistochemically detectable bcl-2 protein. The findings suggest a potential contribution of bcl-2 gene deregulation to the pathogenesis of some types of non-melanoma skin cancer.

The development of non-melanocytic skin cancers in people with a history of skin cancer.

To determine the incidence of new skin cancer formation in people who have had skin cancer removed. A prospective study of Melbourne out-patients with histologically confirmed non-melanoma skin cancer (NMSC). All patients with NMSC seen by one author (D.C.) between November 1988 and November 1989 were entered into the study and reviewed regularly. New skin cancers were removed and recorded. Four hundred and eighty-one patients were entered and 420 followed for at least 3 years. New NMSC developed in 60% (adjusted for losses) by the end of 3 years. A multivariate analysis determined that the main risk factor for new NMSC formation was the number of previous skin cancers that a patient had. Those who had had multiple skin cancers (3 or more) were at significantly greater risk than those with less than 3. Age, sex and type of NMSC were not risk factors for new skin cancer formation. Patients with NMSC require long-term follow-up because of the risk of new skin cancer formation. Those with multiple NMSC need more careful follow-up, and possibly more frequent examinations, because they are at greater risk.

The nordic profile of skin cancer incidence. A comparative epidemiological study of the three main types of skin cancer

The data used for the inter-Nordic comparison of the incidence of skin cancer are based on the material of the national cancer registries of the 5 Nordic countries. It is typical of these countries that the ratio between the incidence of non-melanoma and melanoma skin cancer is much smaller than in regions near the Equator. For the detailed comparative epidemiological study of basal-cell carcinoma (BCC), squamous-cell carcinoma (SCC) and cutaneous malignant melanoma (CMM), the material from the Norwegian Cancer Registry 1955-1988 is used. The etiology of CMM has frequently been debated during recent decades. There are still some obscure points, however, particularly as regards the influence of host factors and UV exposure, and their interaction. The analysis of the incidence trend of CMM on the female breast during the time interval 1970-1988 contributes to the elucidation of these problems. Differences in the epidemiological characteristics of the 2 main types of non-melanoma skin cancer, BCC and SCC, are described. The results indicate that the effect of UV light is not a dominating for BCC as for SCC.