Journal of Skin Cancer http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Basal Cell Carcinoma of the Head and Neck Region: A Retrospective Analysis of Completely Excised 331 Cases Thu, 17 Apr 2014 07:30:33 +0000 http://www.hindawi.com/journals/jsc/2014/858636/ The aim of the study is to analyze all completely excised BCCs in the head and neck region with regard to age, sex, personal and familial history, skin type, tumor localization and size, histopathological subtype of tumor, reconstruction method, and recurrence rates. Incompletely excised BCCs were not included in this study since incomplete excision is the most important preventable risk factor for recurrence. In 320 patients, 331 lesions were retrospectively evaluated by dividing into the following 8 subunits: scalp, frontotemporal, orbital, nose, cheek, auricula, perioral, and chin-neck area. Most of the patients were in 60–70 age group (34.7%). The nose (32.3%) was the most common site of presentation. Clinically, all lesions and, histopathologically, most of the lesions (42.2%) presented were of the nodular type. All cases of recurrence after complete excision (, 2.7%) were located in the median parts of the head and neck region and were mainly diagnosed histopathologically as sclerotic and micronodular. Even though completely excised, head and neck region BCCs, especially which are more prone to recurrence due to anatomical and histopathological properties, should be more closely monitored in order to decrease morbidity and health care costs. Duriye Deniz Demirseren, Candemir Ceran, Berrak Aksam, Mustafa Erol Demirseren, and Ahmet Metin Copyright © 2014 Duriye Deniz Demirseren et al. All rights reserved. Skin Cancer Knowledge, Attitudes, and Behaviors in Collegiate Athletes Mon, 24 Mar 2014 14:24:19 +0000 http://www.hindawi.com/journals/jsc/2014/248198/ Outdoor athletes represent an important group at risk for skin cancer because they are routinely exposed to high levels of ultraviolet radiation. The purpose of this study was to assess current skin cancer knowledge, attitudes, and behaviors among collegiate athletes. A modified version of the Melanoma Risk Behavior Survey was completed by 343 athletes attending a Southern University in the USA, generating an 87% response rate. Survey results demonstrated that the majority of the athletes do not limit their sun exposure and reported low levels of sun protective behaviors. In addition, athletes lacked knowledge about skin cancer and sun protection. Eighty-three percent of the athletes stated that tanning beds improve one’s overall health. Race was significantly associated with skin cancer knowledge, whereas, gender was found to be significantly associated with knowledge, attitudes, and behaviors towards skin cancer. Additionally, there was a significant relationship between knowledge and behavior, but not between attitude and behavior. This study highlights the need to educate athletes about the hazards of tanning to minimize UV exposure and promote sun protection habits. Moreover, athletes should be educated on the dangers of indoor tanning facilities and encouraged to avoid these facilities. Courtney Hobbs, Vinayak K. Nahar, M. Allison Ford, Martha A. Bass, and Robert T. Brodell Copyright © 2014 Courtney Hobbs et al. All rights reserved. Kaposi’s Sarcoma-Associated Herpesvirus Subversion of the Anti-Inflammatory Response in Human Skin Cells Reveals Correlates of Latency and Disease Pathogenesis Mon, 17 Feb 2014 10:00:43 +0000 http://www.hindawi.com/journals/jsc/2014/246076/ KSHV is the etiologic agent for Kaposi’s sarcoma (KS), a neoplasm that manifests most aggressively as multifocal lesions on parts of human skin with a propensity for inflammatory reactivity. However, mechanisms that control evolution of KS from a benign hyperplasia to the histologically complex cutaneous lesion remain unknown. In this study, we found that KSHV induces proteomic and morphological changes in melanocytes and melanoma-derived cell lines, accompanied by deregulation of the endogenous anti-inflammatory responses anchored by the MC1-R/α-MSH signaling axis. We also identified two skin-derived cell lines that displayed differences in ability to support long-term KSHV infection and mapped this dichotomy to differences in (a) NF-κB activation status, (b) processing and expression of KSHV latency-associated nuclear antigen isoforms putatively associated with the viral lytic cycle, and (c) susceptibility to virus-induced changes in expression of key anti-inflammatory response genes that antagonize NF-κB, including MC1-R, POMC, TRP-1, and xCT. Viral subversion of molecules that control the balance between latency and lytic replication represents a novel correlate of KSHV pathogenesis and tropism in skin and underscores the potential benefit of harnessing the endogenous anti-inflammatory processes as a therapeutic option for attenuating cutaneous KS and other proinflammatory outcomes of KSHV infection in high-risk individuals. Judith M. Fontana, Justin G. Mygatt, Katelyn L. Conant, Chris H. Parsons, and Johnan A. R. Kaleeba Copyright © 2014 Judith M. Fontana et al. All rights reserved. Sun-Tanning Perceptions of a New Zealand Urban Population (1994–2005/6) Mon, 10 Feb 2014 07:20:16 +0000 http://www.hindawi.com/journals/jsc/2014/135473/ Background. Sun-tanning perceptions are monitored to identify changes and help refine targeting of skin cancer prevention messages. Aim. To investigate associations between perceptions of sun-tanning and demographic factors among a New Zealand urban population, 1994–2006. Methods. A telephone survey series was conducted during summer in 1994, 1997, 1999/2000, 2002/2003, and 2005/2006. Demographic and personal information (sex, age group, skin sun-sensitivity, and self-defined ethnicity) obtained from 6,195 respondents, 50.2% female, 15–69 years, was investigated in relation to six sun-tanning related statements. A total “positive perceptions of tanning” (ProTan) score was also calculated. Regression analyses modelled each component and the ProTan score against survey year and respondent characteristics. Results. Statistically significantly higher ProTan scores were found for age group (strong reverse dose-response effect), male sex, residence (highest in Auckland), ethnicity (highest among Europeans), and sun sensitivity (an -shaped association). There was no statistically significant change in total ProTan scores from baseline. Conclusions. The development, pretesting, and evaluation of messages for those groups most likely to endorse ProTan statements should be considered for the New Zealand skin cancer prevention program. To achieve and embed significant change, mass media campaigns may require greater intensity and reinforcement with sustained contextual support for settings-based behavioural change. A. I. Reeder, G. F. H. McLeod, A. R. Gray, and R. McGee Copyright © 2014 A. I. Reeder et al. All rights reserved. Histopathological Study of Skin Adnexal Tumours—Institutional Study in South India Wed, 05 Feb 2014 11:52:21 +0000 http://www.hindawi.com/journals/jsc/2014/543756/ Objective. The aim of this study was correlation of skin adnexal tumors with age, sex, and location and determining its incidence in the Department of Pathology at Dr. D. Y. Patil Medical College and Hospital, Kolhapur, Maharashtra. Material and Methods. 56 cases were included in this study from Jan 2004 to June 2010 with respect to incidence of adnexal tumors, age, and sex distribution. All slides were stained with haematoxylin and eosin and then findings were corroborated with special stains like PAS and reticulin wherever required. Results. 80.36% (45/56) were benign and 19.64% (11/56) were malignant adnexal tumors. The sweat gland tumors constituted the largest group (42.86% 24/56) cases followed by the hair follicle tumors (35.71%, 20/56) of cases and sebaceous gland tumors (21.43%, 12/56) cases. Overall male : female ratio was 1.07 : 1. The commonest age group was 51–60 years and the commonest affected body part was head and neck region (64.28%, 36/56) followed by trunk (14.28%, 8/56). Clear cell hidradenoma and pilomatricoma were commonest benign tumors and sebaceous carcinoma was the only malignant tumor seen. Conclusion. The incidence of benign skin adnexal tumors was more as compared to the malignant tumors. Malignant tumors were seen in older age group, usually over 50 years of age. Ankit Sharma, Deepak G. Paricharak, Jitendra Singh Nigam, Shivani Rewri, Priyanka Bhatia Soni, Anita Omhare, and Preethi Sekar Copyright © 2014 Ankit Sharma et al. All rights reserved. Characterization of the Merkel Cell Carcinoma miRNome Mon, 03 Feb 2014 12:03:17 +0000 http://www.hindawi.com/journals/jsc/2014/289548/ MicroRNAs have been implicated in various skin cancers, including melanoma, squamous cell carcinoma, and basal cell carcinoma; however, the expression of microRNAs and their role in Merkel cell carcinoma (MCC) have yet to be explored in depth. To identify microRNAs specific to MCC (MCC-miRs), next-generation sequencing (NGS) of small RNA libraries was performed on different tissue samples including MCCs, other cutaneous tumors, and normal skin. Comparison of the profiles identified several microRNAs upregulated and downregulated in MCC. For validation, their expression was measured via qRT-PCR in a larger group of MCC and in a comparison group of non-MCC cutaneous tumors and normal skin. Eight microRNAs were upregulated in MCC: miR-502-3p, miR-9, miR-7, miR-340, miR-182, miR-190b, miR-873, and miR-183. Three microRNAs were downregulated: miR-3170, miR-125b, and miR-374c. Many of these MCC-miRs, the miR-183/182/96a cistron in particular, have connections to tumorigenic pathways implicated in MCC pathogenesis. In situ hybridization confirmed that the highly expressed MCC-miR, miR-182, is localized within tumor cells. Furthermore, NGS and qRT-PCR reveal that several of these MCC-miRs are highly expressed in the patient-derived MCC cell line, MS-1. These data indicate that we have identified a set of MCC-miRs with important implications for MCC research. Matthew S. Ning, Annette S. Kim, Nripesh Prasad, Shawn E. Levy, Huiqiu Zhang, and Thomas Andl Copyright © 2014 Matthew S. Ning et al. All rights reserved. The Pink Rim Sign: Location of Pink as an Indicator of Melanoma in Dermoscopic Images Mon, 03 Feb 2014 09:06:23 +0000 http://www.hindawi.com/journals/jsc/2014/719740/ Background. In dermoscopic images, multiple shades of pink have been described in melanoma without specifying location of these areas within the lesion. Objective. The purpose of this study was to determine the statistics for the presence of centrally and peripherally located pink melanoma and benign melanocytic lesions. Methods. Three observers, untrained in dermoscopy, each retrospectively analyzed 1290 dermoscopic images (296 melanomas (170 in situ and 126 invasive), 994 benign melanocytic nevi) and assessed the presence of any shade of pink in the center and periphery of the lesion. Results. Pink was located in the peripheral region in 14.5% of melanomas and 6.3% of benign melanocytic lesions, yielding an odds ratio of 2.51 (95% CI: 1.7–3.8, ). Central pink was located in 12.8% of melanomas and 21.8% of benign lesions, yielding an odds ratio of 0.462 (95% CI: 0.67, ). Pink in melanoma in situ tended to be present throughout the lesion (68% of pink lesions). Pink in invasive melanoma was present in 17% of cases, often presenting as a pink rim. Conclusions. The presence of pink in the periphery or rim of a dermoscopic melanocytic lesion image provides an indication of malignancy. We offer the “pink rim sign” as a clue to the dermoscopic diagnosis of invasive melanoma. Ryan K. Rader, Katie S. Payne, Uday Guntupalli, Harold S. Rabinovitz, Maggie C. Oliviero, Rhett J. Drugge, Joseph J. Malters, and William V. Stoecker Copyright © 2014 Ryan K. Rader et al. All rights reserved. Gene Expression Differences Predict Treatment Outcome of Merkel Cell Carcinoma Patients Thu, 30 Jan 2014 09:20:41 +0000 http://www.hindawi.com/journals/jsc/2014/596459/ Due to the rarity of Merkel cell carcinoma (MCC), prospective clinical trials have not been practical. This study aimed to identify biomarkers with prognostic significance. While sixty-two patients were identified who were treated for MCC at our institution, only seventeen patients had adequate formalin-fixed paraffin-embedded archival tissue and followup to be included in the study. Patients were stratified into good, moderate, or poor prognosis. Laser capture microdissection was used to isolate tumor cells for subsequent RNA isolation and gene expression analysis with Affymetrix GeneChip Human Exon 1.0 ST arrays. Among the 191 genes demonstrating significant differential expression between prognostic groups, keratin 20 and neurofilament protein have previously been identified in studies of MCC and were significantly upregulated in tumors from patients with a poor prognosis. Immunohistochemistry further established that keratin 20 was overexpressed in the poor prognosis tumors. In addition, novel genes of interest such as phospholipase A2 group X, kinesin family member 3A, tumor protein D52, mucin 1, and KIT were upregulated in specimens from patients with poor prognosis. Our pilot study identified several gene expression differences which could be used in the future as prognostic biomarkers in MCC patients. Loren Masterson, Bryan J. Thibodeau, Laura E. Fortier, Timothy J. Geddes, Barbara L. Pruetz, Rajwant Malhotra, Richard Keidan, and George D. Wilson Copyright © 2014 Loren Masterson et al. All rights reserved. Surgical Excision with Forehead Flap as Single Modality Treatment for Basal Cell Cancer of Central Face: Single Institutional Experience of 50 Cases Tue, 28 Jan 2014 08:15:43 +0000 http://www.hindawi.com/journals/jsc/2014/320792/ Basal cell carcinoma (BCC) is the most common skin cancer worldwide. The WHO has defined it as “a locally invasive, slowly spreading tumor which rarely metastasizes, arising in the epidermis or hair follicles and in which the peripheral cells usually simulate the basal cells of the epidermis.” Here we discuss the management of BCCs of central face with surgical excision and reconstruction with forehead flap as single modality treatment. Material and Methods. This is a retrospective review of 50 patients who underwent surgical excision of BCC involving the facial region followed by primary reconstruction using forehead flaps at a single institution. There were 20 males and 30 females, mean age of 59 years. Results. No recurrence at primary site was observed during the follow-up of 1–4 yrs. There was no ectropion or exposure sequela. However, epiphora was evident. Size of lesions ranged from 2 to 6 cm. Keloid formation was seen in 2 (4%) patients. Functional and cosmetic outcomes were satisfactory. Conclusion. For the face, the best reconstructive effort eventually fails in the face of tumor recurrence. The forehead flap represents one of the best methods for repair of extensive facial defects. Complete tumor extirpation, the primary event, is the key. Jagdeep Rao and Harsh Deora Copyright © 2014 Jagdeep Rao and Harsh Deora. All rights reserved. Prediction of Sentinel Node Status and Clinical Outcome in a Melanoma Centre Wed, 25 Dec 2013 08:32:06 +0000 http://www.hindawi.com/journals/jsc/2013/904701/ Background. Sentinel lymph node biopsy (SLNB) is a standard procedure for patients with localized cutaneous melanoma. The National Comprehensive Cancer Network (NCCN) Melanoma Panel has reinforced the status of the sentinel lymph node (SLN) as an important prognostic factor for melanoma survival. We sought to identify predictive factors associated with a positive SLNB and overall survival in our population. Methods. We performed a retrospective chart review of 221 patients who have done a successful SLNB for melanoma between 2004 and 2010 at our department. Univariate and multivariate analyses were done. Results. The SLNB was positive in 48 patients (21.7%). Univariate analysis showed that male gender, increasing Breslow thickness, tumor type, and absence of tumor-infiltrating lymphocytes were significantly associated with a positive SLNB. Multivariate analysis confirmed that Breslow thickness and the absence of tumor-infiltrating lymphocytes are independently predictive of SLN metastasis. The 5-year survival rates were 53.1% for SLN positive patients and 88.2% for SLN negative patients. Breslow thickness and the SLN status independently predict overall survival. Conclusions. The risk factors for a positive SLNB are consistent with those found in the previous literature. In addition, the SLN status is a major determinant of survival, which highlights its importance in melanoma management. Vera Teixeira, Ricardo Vieira, Inês Coutinho, Rita Cabral, David Serra, Maria José Julião, Maria Manuel Brites, Anabela Albuquerque, João Pedroso de Lima, and Américo Figueiredo Copyright © 2013 Vera Teixeira et al. All rights reserved. Extended UVB Exposures Alter Tumorigenesis and Treatment Efficacy in a Murine Model of Cutaneous Squamous Cell Carcinoma Sun, 27 Oct 2013 17:45:02 +0000 http://www.hindawi.com/journals/jsc/2013/246848/ Epidemiological studies support a link between cumulative sun exposure and cutaneous squamous cell carcinoma (SCC) development. However, the presumed effects of extended ultraviolet light B (UVB) exposure on tumorigenesis in the sexes have not been formally investigated. We examined differences in ultimate tumorigenesis at 25 weeks in mice exposed to UVB for either 10 or 25 weeks. Additionally, we investigated the effect of continued UVB exposure on the efficacy of topical treatment with anti-inflammatory (diclofenac) or antioxidant (C E Ferulic or vitamin E) compounds on modulating tumorigenesis. Vehicle-treated mice in the 25-week UVB exposure model exhibited an increased tumor burden and a higher percentage of malignant tumors compared to mice in the 10-week exposure model, which correlated with increases in total and mutant p53-positive epidermal cells. Only topical diclofenac decreased tumor number and burden in both sexes regardless of UVB exposure length. These data support the commonly assumed but not previously demonstrated fact that increased cumulative UVB exposure increases the risk of UVB-induced SCC development and can also affect therapeutic efficacies. Our study suggests that cessation of UVB exposure by at-risk patients may decrease tumor development and that topical NSAIDs such as diclofenac may be chemopreventive. Erin M. Burns, Kathleen L. Tober, Judith A. Riggenbach, Donna F. Kusewitt, Gregory S. Young, and Tatiana M. Oberyszyn Copyright © 2013 Erin M. Burns et al. All rights reserved. Sociodemographic and Psychological Correlates of Sun Protection Behaviors among Outdoor Workers: A Review Tue, 22 Oct 2013 14:06:39 +0000 http://www.hindawi.com/journals/jsc/2013/453174/ Outdoor workers are at a higher risk for developing skin cancer due to their increased sun exposure. The primary objective of this review was to synthesize the current research literature that addresses sociodemographic and psychological factors related to sun protection behaviors in outdoor workers. Two additional purposes were to provide an overview of sun exposure and describe sun protection behaviors of outdoor workers. To identify the studies for this review, a methodical search was performed in the PubMed, PsycInfo, MEDLINE, and ERIC databases. Fifteen studies met the review criteria. Despite regular and prolonged sun exposure, many outdoor workers fail to engage in sufficient sun protection behaviors. Correlates of outdoor workers’ sun protection behaviors include being female, older age, being white, personal skin cancer history, time (hours/years) spent at work, sun safety training, perceived prioritization of sun protection, concern about sun exposure, workplace support, families’ expectations, and familial information giving. However, limited attention is given to designing theoretically grounded studies to identify factors to inform future research. There is a need to conduct research based on solid theoretical foundations that explains the relationships among the factors in this domain. Vinayak K. Nahar, M. Allison Ford, Jeffrey S. Hallam, Martha A. Bass, and Michael A. Vice Copyright © 2013 Vinayak K. Nahar et al. All rights reserved. Identification of DLEC1 D215N Somatic Mutation in Formalin Fixed Paraffin Embedded Melanoma and Melanocytic Nevi Specimens Sun, 13 Oct 2013 15:14:07 +0000 http://www.hindawi.com/journals/jsc/2013/469671/ DLEC1 has been suggested as a tumor suppressor gene in several cancers. DLEC1 D215N somatic mutation (COSM36702) was identified in a melanoma cell line through whole genome sequencing. However, little is known about the implication and prevalence of this mutation in primary melanomas or in melanocytic nevi. The aim of this study was to genotype DLEC1 D215N mutation in melanoma tissue and melanocytic nevi samples to confirm its occurrence and to estimate its prevalence. Primary melanomas () paired with synchronous or asynchronous metastases () from 81 melanoma patients and melanocytic nevi () were screened for DLEC1 D215N mutation. We found the mutation in 3 primary melanomas and in 2 melanocytic nevi, corresponding to a relatively low prevalence (3.7% and 7.1%, resp.). The pathogenic role of DLEC1 215N mutation is unclear. However, since the mutation has not been previously described in general population, its involvement in nevogenesis and melanoma progression remains a possibility to be clarified in future studies. Ricardo Vieira, Maria José Simões, Susana Carmona, Conceição Egas, Carlos Faro, and Américo Figueiredo Copyright © 2013 Ricardo Vieira et al. All rights reserved. Melanoma in Buckinghamshire: Data from the Inception of the Skin Cancer Multidisciplinary Team Mon, 16 Sep 2013 11:14:20 +0000 http://www.hindawi.com/journals/jsc/2013/843282/ Background. Melanoma incidence is increasing faster than any other cancer in the UK. The introduction of specialist skin cancer multidisciplinary teams intends to improve the provision of care to patients suffering from melanoma. This study aims to investigate the management and survival of patients diagnosed with melanoma around the time of inception of the regional skin cancer multidisciplinary team both to benchmark the service against published data and to enable future analysis of the impact of the specialisation of skin cancer care. Methods. All patients diagnosed with primary cutaneous melanoma between January 1, 2003 and December 3, 2005 were identified. Data on clinical and histopathological features, surgical procedures, complications, disease recurrence and 5-year survival were collected and analysed. Results. Two hundred and fourteen patients were included, 134 female and 80 males. Median Breslow thickness was 0.74 mm (0.7 mm female and 0.8 mm male). Overall 5-year survival was 88% (90% female and 85% male). Discussion. Melanoma incidence in Buckinghamshire is in keeping with published data. Basic demographics details concur with classic melanoma distribution and more recent trends, with increased percentage of superficial spreading and thin melanomas, leading to improved survival are reflected. J. J. Cubitt, A. A. Khan, E. Royston, M. Rughani, M. R. Middleton, and P. G Budny Copyright © 2013 J. J. Cubitt et al. All rights reserved. Merkel Cell Carcinoma of the Head and Neck: Challenges in Diagnosis and Therapy Tue, 10 Sep 2013 15:14:05 +0000 http://www.hindawi.com/journals/jsc/2013/427984/ Brett A. Miles Copyright © 2013 Brett A. Miles. All rights reserved. Ambulatory Melanoma Care Patterns in the United States Wed, 21 Aug 2013 10:34:24 +0000 http://www.hindawi.com/journals/jsc/2013/689261/ Objective. To examine trends in melanoma visits in the ambulatory care setting. Methods. Data from the National Ambulatory Medical Care Survey (NAMCS) from 1979 to 2010 were used to analyze melanoma visit characteristics including number of visits, age and gender of patients, and physician specialty. These data were compared to US Census population estimates during the same time period. Results. The overall rate of melanoma visits increased () at an apparently higher rate than the increase in population over this time. The age of patients with melanoma visits increased at approximately double the rate (0.47 year per interval year, ) of the population increase in age (0.23 year per interval year). There was a nonsignificant decline in the proportion of female patients seen over the study interval. Lastly, ambulatory care has shifted towards dermatologists and other specialties managing melanoma patients and away from family/internal medicine physicians and general/plastic surgeons. Conclusions. The number and age of melanoma visits has increased over time with respect to the overall population, mirroring the increase in melanoma incidence over the past three decades. These trends highlight the need for further studies regarding melanoma management efficiency. Andrew L. Ji, Michael R. Baze, Scott A. Davis, Steven R. Feldman, and Alan B. Fleischer Jr. Copyright © 2013 Andrew L. Ji et al. All rights reserved. Simulators of Squamous Cell Carcinoma of the Skin: Diagnostic Challenges on Small Biopsies and Clinicopathological Correlation Tue, 25 Jun 2013 17:11:58 +0000 http://www.hindawi.com/journals/jsc/2013/752864/ Squamous cell carcinoma (SCC) is a common and important primary cutaneous malignancy. On skin biopsies, SCC is characterized by significant squamous cell atypia, abnormal keratinization, and invasive features. Diagnostic challenges may occasionally arise, especially in the setting of small punch biopsies or superficial shave biopsies, where only part of the lesion may be assessable by the pathologist. Benign mimics of SCC include pseudoepitheliomatous hyperplasia, eccrine squamous syringometaplasia, inverted follicular keratosis, and keratoacanthoma, while malignant mimics of SCC include basal cell carcinoma, melanoma, and metastatic carcinoma. The careful application of time-honored diagnostic criteria, close clinicopathological correlation and a selective request for a further, deeper, or wider biopsy remain the most useful strategies to clinch the correct diagnosis. This review aims to present the key differential diagnoses of SCC, to discuss common diagnostic pitfalls, and to recommend ways to deal with diagnostically challenging cases. Kong-Bing Tan, Sze-Hwa Tan, Derrick Chen-Wee Aw, Huma Jaffar, Thiam-Chye Lim, Shu-Jin Lee, and Yoke-Sun Lee Copyright © 2013 Kong-Bing Tan et al. All rights reserved. Potential Role of Meiosis Proteins in Melanoma Chromosomal Instability Wed, 12 Jun 2013 10:32:51 +0000 http://www.hindawi.com/journals/jsc/2013/190109/ Melanomas demonstrate chromosomal instability (CIN). In fact, CIN can be used to differentiate melanoma from benign nevi. The exact molecular mechanisms that drive CIN in melanoma have yet to be fully elucidated. Cancer/testis antigens are a unique group of germ cell proteins that are found to be primarily expressed in melanoma as compared to benign nevi. The abnormal expression of these germ cell proteins, normally expected only in the testis and ovaries, in somatic cells may lead to interference with normal cellular pathways. Germ cell proteins that may be particularly critical in CIN are meiosis proteins. Here, we review pathways unique to meiosis with a focus on how the aberrant expression of meiosis proteins in normal mitotic cells “meiomitosis” could impact chromosomal instability in melanoma and other cancers. Scott F. Lindsey, Diana M. Byrnes, Mark S. Eller, Ashley M. Rosa, Nitika Dabas, Julia Escandon, and James M. Grichnik Copyright © 2013 Scott F. Lindsey et al. All rights reserved. Sunscreen Use on the Dorsal Hands at the Beach Thu, 06 Jun 2013 14:17:10 +0000 http://www.hindawi.com/journals/jsc/2013/269583/ Background. Since skin of the dorsal hands is a known site for the development of cutaneous squamous cell carcinoma, an epidemiologic investigation was needed to determine if beachgoers apply sunscreen to the dorsal aspect of their hands as frequently as they apply it to other skin sites. Aim. The aim of the current study was to compare the use of sunscreen on the dorsal hands to other areas of the body during subtropical late spring and summer sunlight exposure at the beach. Materials and Methods. A cross-sectional survey from a convenience sample of beachgoers was designed to evaluate respondent understanding and protective measures concerning skin cancer on the dorsal hands in an environment with high natural UVR exposure. Results. A total of 214 surveys were completed and analyzed. Less than half of subjects (105, 49%) applied sunscreen to their dorsal hands. Women applied sunscreen to the dorsal hands more than men (55% women versus 40% men, ). Higher Fitzpatrick Skin Type respondents were less likely to protect their dorsal hands from ultraviolet radiation (). Conclusions. More public education focused on dorsal hand protection from ultraviolet radiation damage is necessary to reduce the risk for squamous cell carcinomas of the hands. Donald B. Warren, Ryan R. Riahi, Jason B. Hobbs, and Richard F. Wagner Jr. Copyright © 2013 Donald B. Warren et al. All rights reserved. Mouse Models of the Skin: Models to Define Mechanisms of Skin Carcinogenesis Sun, 02 Jun 2013 09:10:25 +0000 http://www.hindawi.com/journals/jsc/2013/971495/ Deric L. Wheeler, Ajit K. Verma, and Mitchell F. Denning Copyright © 2013 Deric L. Wheeler et al. All rights reserved. AP1 Transcription Factors in Epidermal Differentiation and Skin Cancer Thu, 23 May 2013 13:35:43 +0000 http://www.hindawi.com/journals/jsc/2013/537028/ AP1 (jun/fos) transcription factors (c-jun, junB, junD, c-fos, FosB, Fra-1, and Fra-2) are key regulators of epidermal keratinocyte survival and differentiation and important drivers of cancer development. Understanding the role of these factors in epidermis is complicated by the fact that each protein is expressed, at different levels, in multiple cells layers in differentiating epidermis, and because AP1 transcription factors regulate competing processes (i.e., proliferation, apoptosis, and differentiation). Various in vivo genetic approaches have been used to study these proteins including targeted and conditional knockdown, overexpression, and expression of dominant-negative inactivating AP1 transcription factors in epidermis. Taken together, these studies suggest that individual AP1 transcription factors have different functions in the epidermis and in cancer development and that altering AP1 transcription factor function in the basal versus suprabasal layers differentially influences the epidermal differentiation response and disease and cancer development. Richard L. Eckert, Gautam Adhikary, Christina A. Young, Ralph Jans, James F. Crish, Wen Xu, and Ellen A. Rorke Copyright © 2013 Richard L. Eckert et al. All rights reserved. Ipilimumab: A First-in-Class  T-Cell Potentiator for Metastatic Melanoma Wed, 08 May 2013 08:10:43 +0000 http://www.hindawi.com/journals/jsc/2013/423829/ Ipilimumab, a fully human anti-cytotoxic T-lymphocyte antigen-4 monoclonal antibody that potentiates antitumor T-cell responses, has demonstrated improved survival in previously treated and treatment-naïve patients with unresectable stage III/IV melanoma. Survival benefit has also been shown in diverse patient populations, including those with brain metastases. In 2011, ipilimumab (3 mg/kg every 3 weeks for 4 doses) was approved by the Food and Drug Administration for unresectable or metastatic melanoma. Ipilimumab can induce novel response patterns for which immune-related response criteria have been proposed. irAEs are common but are usually low grade; higher grades can be severe and life-threatening. irAEs are usually manageable using established guidelines emphasizing vigilance and prompt intervention. This agent provides an additional therapeutic option in metastatic melanoma, and guidelines for management of adverse events facilitate clinical implementation of this new agent. Bartosz Chmielowski Copyright © 2013 Bartosz Chmielowski. All rights reserved. Protein Kinase Cε, Which Is Linked to Ultraviolet Radiation-Induced Development of Squamous Cell Carcinomas, Stimulates Rapid Turnover of Adult Hair Follicle Stem Cells Mon, 29 Apr 2013 09:00:14 +0000 http://www.hindawi.com/journals/jsc/2013/452425/ To find clues about the mechanism by which kinase C epsilon (PKCε) may impart susceptibility to ultraviolet radiation (UVR)-induced development of cutaneous squamous cell carcinomas (SCC), we compared PKCε transgenic (TG) mice and their wild-type (WT) littermates for (1) the effects of UVR exposures on percent of putative hair follicle stem cells (HSCs) and (2) HSCs proliferation. The percent of double HSCs (CD34+ and α6-integrin or CD34+/CD49f+) in the isolated keratinocytes were determined by flow cytometric analysis. Both single and chronic UVR treatments (1.8 kJ/m2) resulted in an increase in the frequency of double positive HSCs in PKCε TG mice as compared to their WT littermates. To determine the rate of proliferation of bulge region stem cells, a 5-bromo-2′-deoxyuridine labeling (BrdU) experiment was performed. In the WT mice, the percent of double positive HSCs retaining BrdU label was % compared to % for the TG mice, an approximately 7-fold decrease. A comparison of gene expression profiles of FACS sorted double positive HSCs showed increased expression of Pes1, Rad21, Tfdp1 and Cks1b genes in TG mice compared to WT mice. Also, PKCε over expression in mice increased the clonogenicity of isolated keratinocytes, a property commonly ascribed to stem cells. Ashok Singh, Anupama Singh, Jordan M. Sand, Erika Heninger, Bilal Bin Hafeez, and Ajit K. Verma Copyright © 2013 Ashok Singh et al. All rights reserved. Delineating Molecular Mechanisms of Squamous Tissue Homeostasis and Neoplasia: Focus on p63 Mon, 22 Apr 2013 09:35:26 +0000 http://www.hindawi.com/journals/jsc/2013/632028/ Mouse models have informed us that p63 is critical for normal epidermal development and homeostasis. The p53/p63/p73 family is expressed as multiple protein isoforms due to a combination of alternative promoter usage and C-terminal alternative splicing. These isoforms can mimic or interfere with one another, and their balance ultimately determines biological outcome in a context-dependent manner. While not frequently mutated, p63, and in particular the ΔNp63 subclass, is commonly overexpressed in human squamous cell cancers. In vitro keratinocytes and murine transgenic and transplantation models have been invaluable in elucidating the contribution of altered p63 levels to cancer development, and studies have identified the roles for ΔNp63 isoforms in keratinocyte survival and malignant progression, likely due in part to their transcriptional regulatory function. These findings can be extended to human cancers; for example, the novel recognition of NFκB/c-Rel as a downstream effector of p63 has identified a role for NFκB/c-Rel in human squamous cell cancers. These models will be critical in enhancing the understanding of the specific molecular mechanisms of cancer development and progression. Kathryn E. King, Linan Ha, Tura Camilli, and Wendy C. Weinberg Copyright © 2013 Kathryn E. King et al. All rights reserved. Merkel Cell Carcinoma: The Past, the Present, and the Future Tue, 16 Apr 2013 08:34:28 +0000 http://www.hindawi.com/journals/jsc/2013/929364/ Since the first description of the Merkel cell carcinoma by Cyril Toker in 1972, the number of studies has significantly increased over the last 4 decades. In this review, we will illustrate the historical background of the Merkel cell carcinoma beginning with the 19th century, the first description of the Merkel cell to the finding of the CK20 as a highly specific diagnostic marker and finally to the recently detected Merkel cell polyomavirus (MCPyV). Moreover, we will highlight the beginning of adjuvant therapeutic regimens with radiotherapy and chemotherapy and discuss the diagnostic work-up including imaging and histology of patients with Merkel cell carcinoma. Another very rapidly growing and interesting field of research is the development of patients' specific and tailored targeted therapy, in particular in patients with distant metastatic disease. Inamaria Erovic and Boban M. Erovic Copyright © 2013 Inamaria Erovic and Boban M. Erovic. All rights reserved. Role of Stat3 in Skin Carcinogenesis: Insights Gained from Relevant Mouse Models Thu, 21 Mar 2013 13:16:52 +0000 http://www.hindawi.com/journals/jsc/2013/684050/ Signal transducer and activator of transcription 3 (Stat3) is a cytoplasmic protein that is activated in response to cytokines and growth factors and acts as a transcription factor. Stat3 plays critical roles in various biological activities including cell proliferation, migration, and survival. Studies using keratinocyte-specific Stat3-deficient mice have revealed that Stat3 plays an important role in skin homeostasis including keratinocyte migration, wound healing, and hair follicle growth. Use of both constitutive and inducible keratinocyte-specific Stat3-deficient mouse models has demonstrated that Stat3 is required for both the initiation and promotion stages of multistage skin carcinogenesis. Further studies using a transgenic mouse model with a gain of function mutant of Stat3 (Stat3C) expressed in the basal layer of the epidermis revealed a novel role for Stat3 in skin tumor progression. Studies using similar Stat3-deficient and gain-of-function mouse models have indicated its similar roles in ultraviolet B (UVB) radiation-mediated skin carcinogenesis. This paper summarizes the use of these various mouse models for studying the role and underlying mechanisms for the function of Stat3 in skin carcinogenesis. Given its significant role throughout the skin carcinogenesis process, Stat3 is an attractive target for skin cancer prevention and treatment. Everardo Macias, Dharanija Rao, and John DiGiovanni Copyright © 2013 Everardo Macias et al. All rights reserved. Latest Approved Therapies for Metastatic Melanoma: What Comes Next? Sun, 24 Feb 2013 09:42:39 +0000 http://www.hindawi.com/journals/jsc/2013/735282/ Nowadays, oncogene-directed therapy and immunotherapy represent the two most promising avenues for patients with metastatic melanoma. The recent oncogene-directed therapeutic, vemurafenib, usually produces high level of tumor shrinkage and survival benefits in many patients with B-RA mutant melanomas, although the fast and high degrees of responses are likely short-lived. Conversely, the newly-approved immunotherapeutic, ipilimumab, produces durable responses in patients presenting CTLA-4 T-cell surface protein. Nevertheless, the possible synergy in combining these two therapeutic strategies primarily rely on the rational design of medical protocols (e.g., sequence and timing of agent administration; drug selectivity; compatibility of combined therapies i.e., adoptive T cell or agents, i.e., MEK inhibitor trametinib, PD-1 and PDL-1 blockers). Improved therapeutic protocols shall overcome therapeutic limitations such as the (i) tolerability and safety (i.e., minimal toxic side-effects); (ii) progression free survival (e.g., reduced relapse disease frequency); (iii) duration response (i.e., decreased drug resistance). Eventually, multidisciplinary approaches are still requested (e.g., genomics for personalized medicine, nanomedicine to overcome low free-drug bioavailability and targeting, systematic search of “melanoma stem cells” to enhance the prognosis and develop more valuable theranostics). In this paper, I will mainly present and discuss the latest and promising treatments for advanced cutaneous melanomas. Farid Menaa Copyright © 2013 Farid Menaa. All rights reserved. Melanoma-Targeted Chemothermotherapy and In Situ Peptide Immunotherapy through HSP Production by Using Melanogenesis Substrate, NPrCAP, and Magnetite Nanoparticles Thu, 21 Feb 2013 12:59:18 +0000 http://www.hindawi.com/journals/jsc/2013/742925/ Exploitation of biological properties unique to cancer cells may provide a novel approach to overcome difficult challenges to the treatment of advanced melanoma. In order to develop melanoma-targeted chemothermoimmunotherapy, a melanogenesis substrate, N-propionyl-4-S-cysteaminylphenol (NPrCAP), sulfur-amine analogue of tyrosine, was conjugated with magnetite nanoparticles. NPrCAP was exploited from melanogenesis substrates, which are expected to be selectively incorporated into melanoma cells and produce highly reactive free radicals through reacting with tyrosinase, resulting in chemotherapeutic and immunotherapeutic effects by oxidative stress and apoptotic cell death. Magnetite nanoparticles were conjugated with NPrCAP to introduce thermotherapeutic and immunotherapeutic effects through nonapoptotic cell death and generation of heat shock protein (HSP) upon exposure to alternating magnetic field (AMF). During these therapeutic processes, NPrCAP was also expected to provide melanoma-targeted drug delivery system. Kowichi Jimbow, Yasue Ishii-Osai, Shosuke Ito, Yasuaki Tamura, Akira Ito, Akihiro Yoneta, Takafumi Kamiya, Toshiharu Yamashita, Hiroyuki Honda, Kazumasa Wakamatsu, Katsutoshi Murase, Satoshi Nohara, Eiichi Nakayama, Takeo Hasegawa, Itsuo Yamamoto, and Takeshi Kobayashi Copyright © 2013 Kowichi Jimbow et al. All rights reserved. Sentinel Lymph Node Biopsy in Nonmelanoma Skin Cancer Patients Thu, 14 Feb 2013 14:49:02 +0000 http://www.hindawi.com/journals/jsc/2013/267474/ The management of lymph nodes in nonmelanoma skin cancer patients is currently still debated. Merkel cell carcinoma (MCC), squamous cell carcinoma (SCC), pigmented epithelioid melanocytoma (PEM), and other rare skin neoplasms have a well-known risk to spread to regional lymph nodes. The use of sentinel lymph node biopsy (SLNB) could be a promising procedure to assess this risk in clinically N0 patients. Metastatic SNs have been observed in 4.5–28% SCC (according to risk factors), in 9–42% MCC, and in 14–57% PEM. We observed overall 30.8% positive SNs in 13 consecutive patients operated for high-risk nonmelanoma skin cancer between 2002 and 2011 in our institution. These high rates support recommendation to implement SLNB for nonmelanoma skin cancer especially for SCC patients. Completion lymph node dissection following positive SNs is also a matter of discussion especially in PEM. It must be remembered that a definitive survival benefit of SLNB in melanoma patients has not been proven yet. However, because of its low morbidity when compared to empiric elective lymph node dissection or radiation therapy of lymphatic basins, SLNB has allowed sparing a lot of morbidity and could therefore be used in nonmelanoma skin cancer patients, even though a significant impact on survival has not been demonstrated. Marie-Laure Matthey-Giè, Ariane Boubaker, Igor Letovanec, Nicolas Demartines, and Maurice Matter Copyright © 2013 Marie-Laure Matthey-Giè et al. All rights reserved. Merkel Cell Carcinoma: Chemotherapy and Emerging New Therapeutic Options Sun, 10 Feb 2013 11:23:37 +0000 http://www.hindawi.com/journals/jsc/2013/327150/ Merkel cell carcinoma (MCC) is a rare neuroendocrine skin tumor that typically occurs in elderly, immunosuppressed patients. Infection with Merkel cell virus (MCV) and immunosuppression play an important role in the development of MCC. Different staging systems make it difficult to compare the existing clinical data. Furthermore, there predominantly exist single case reports and case series, but no randomized controlled trials. However, it is necessary to develop further therapy options because MCC tends to grow rapidly and metastasizes early. In the metastatic disease, therapeutic attempts were made with various chemotherapeutic combination regimens. Because of the high toxicity of these combinations, especially those established in SCLC, and regarding the unsatisfying results, the challenge is to balance the pros and cons of chemotherapy individually and carefully. Up to now, emerging new therapy options as molecular-targeted agents, for example, pazopanib, imatinib, or somatostatin analogues as well as immunologicals, for example, imiquimod and interferons, also showed less success concerning the disease-free response rates. According to the literature, neither chemotherapy nor molecular-targeted agents or immunotherapeutic strategies have shown promising effects in the therapy of the metastatic disease of MCC so far. There is a great demand for randomized controlled studies and a need for an MCC registry and multicenter clinical trials due to the tumors curiosity. Laura Desch and Rainer Kunstfeld Copyright © 2013 Laura Desch and Rainer Kunstfeld. All rights reserved.