Types Of Skin Tumors Research Articles

Prevalence of tumors in dogs from the municipality of Toluca, México, from 2002 to 2008

SUMMARY The purpose of this study was to estimate the prevalence of tumors in biopsies of owned dogs sent to the pathology laboratory from the municipality of Toluca. Tissue samples (n = 172) were received at CIESA laboratory from 2002 to 2008. The estimated prevalence was 1.23/1000 dogs, with values of 1.37 for bitches 1.08 for males. The frequency of tumors per age group was: 59.3% in dogs of 7-15 years old, 33.7% in dogs of 2-6 years old and 7% in dogs younger than 2 years old. Skin tumors were the most prevalent (0.65), followed by mammary gland tumors (0.24). These results suggested that age could be associated to the presence of malignant tumors, and that UV radiation could be associated to the appearance of certain types of skin tumors. This study contributes to the understanding of the epidemiology of tumors in dogs from Toluca, in order to establish the first registry of dog tumors in Mexico.

Skin Cancer After Solid Organ Transplantation

Sir, We read the article by Belloni-Fortina et al. (1) with great interest. This retrospective study focused on the incidence of, and risk factors for, skin complications among liver transplant patients. They concluded that in these recipients the risk of premalignant and malignant skin lesions was lower than that of other solid organ transplants. Although organ transplant recipients are predisposed to the development of skin cancers, the epidemiology of skin tumours following organ transplantation varies geographically (2, 3); therefore, the lower rate of skin cancer in the study of Belloni-Fortina et al. (1) may reflect geographical differences. We have previously reported on the low rate of skin tumours among Iranian kidney transplant patients (2, 3). The overall incidence of skin tumors in 11,255 kidney transplant recipients was 1.14%, representing half of all post-transplant malignancies (128 out of 245 cases) (2). Kaposi’s sarcoma was the most common tumour type (2, 3); the incidence of Kaposi’s sarcoma is greatly increased among transplant patients in the Middle East countries (4, 5). Belloni-Fortina et al. (1) showed that male sex (maleto-female ratio of 6:1) and advanced age increased the risk of skin tumours after liver transplantation. In our study, male recipients also had more skin cancers (male:female ratio of 2.5:1), and individuals older than 45 years were at higher risk (odds ratio 3.8) (2). Although Belloni-Fortina et al. (1) found azathioprine as a second immunosuppressant was not a risk factor for the development of skin cancer, we observed that recipients who were on azathioprine were more likely to develop skin tumours when compared with those treated with mycophenolate mofetil (odds ratio 2.9) (2). In conclusion, the types of skin tumours following organ transplantation vary geographically, and the incidence and risk factors for these tumours appear to differ be tween countries.

Basal Cell Carcinoma in African-Americans: Two Case Reports

Introduction: Basal Cell Carcinoma (BCC) is the less aggressive type of skin tumor. It consists of cells which resemble epidermis basal cells, and metastases are described as exceptions. However, it can invade and destroy adjacent tissues, including bones. It is the most common cutaneous malignancy, with 65% of the total. It usually occurs after 40 years old, with sun exposure and fair skin as related factors, being rare in African-Americans. BCC is generally located on sun-exposed areas, like face (nose, ears and neck) and less commonly in trunk and extremities. The most frequent skin cancer in blacks is Squamous Cell Carcinoma, followed by BCC. There are different histologic patterns in BCC and the main characteristic is the presence of palisade basaloid cells masses arranged peripherally. The diagnosis is clinical and must be confirmed histologically. The choice for therapeutic procedures depends on the location, size and depth of the lesion. Case Reports: Case 1: A 53-years-old male, black, husbandman, presenting plaque lesion with pearly and pigmented edges on the nasal dorsum. Wide resection was made with safety margin, followed by reconstruction with a graft of frontal region. Case 2: A 57-years-old male, black, husbandman, presenting nodular-ulcerated lesion with pearly and pigmented edges on the right nasal ala. The resection with a wide safety margin was made, followed by reconstruction with graft of right genian region, bent at its end to reconstructing the inner portion of the nostril after two weeks. The diagnosis was confirmed through histopathology, which showed clear surgical margins. Discussion: Skin cancer affects mainly Caucasian people. It is rare in blacks, because the higher melanin content and dispersion pattern of melanosomes protect against the carcinogenic effects of sunlight. These cases are rare, but confirmed that ultraviolet radiation is an important risk factor for skin cancer, especially BCC. These two patients were over 40 years old; group most affected by skin cancer, and was submitted to prolonged sun exposure. Surgical resection was curative in both cases, since it was accomplished with good safety margin.

Genome-Wide Analysis of Gene and Protein Expression of Dysplastic Naevus Cells

Cutaneous melanoma, a type of skin tumor originating from melanocytes, often develops from premalignant naevoid lesions via a gradual transformation process driven by an accumulation of (epi)genetic lesions. These dysplastic naevi display altered morphology and often proliferation of melanocytes. Additionally, melanocytes in dysplastic naevi show structural mitochondrial and melanosomal alterations and have elevated reactive oxygen species (ROS) levels. For this study we performed genome-wide expression and proteomic analysis of melanocytes from dysplastic naevus (DNMC) and adjacent normal skin (MC) from 18 patients. Whole genome expression profiles of the DNMC and MC of each individual patient subjected to GO-based comparative statistical analysis yielded significantly differentially expressed GO classes including “organellar ribosome,” “mitochondrial ribosome,” “hydrogen ion transporter activity,” and “prefoldin complex.” Validation of 5 genes from these top GO classes revealed a heterogeneous differential expression pattern. Proteomic analysis demonstrated differentially expressed proteins in DNMC that are involved in cellular metabolism, detoxification, and cytoskeletal organization processes, such as GTP-binding Rho-like protein CDC42, glutathione-S-transferase omega-1 and prolyl 4-hydroxylase. Collectively these results point to deregulation of cellular processes, such as metabolism and protein synthesis, consistent with the observed elevated oxidative stress levels in DNMC potentially resulting in oxidative DNA damage in these cells.

Identification of the most common cutaneous neoplasms in dogs and evaluation of breed and age distributions for selected neoplasms

OBJECTIVE-To identify the most common cutaneous neoplasms in dogs and evaluate breed and age distributions for selected neoplasms. DESIGN-Retrospective epidemiological study. SAMPLE-Records available through the Veterinary Medical Database of dogs examined at veterinary teaching hospitals in North America between 1964 and 2002. PROCEDURES-Information on tumor type and patient breed and age was collected. Incidence and odds ratios with 95% confidence intervals were calculated. RESULTS-Records of 1,139,616 dogs were reviewed. Cutaneous neoplasms were diagnosed in 25,996 of these dogs; records for the remaining 1,113,620 dogs did not indicate that cutaneous neoplasms had been diagnosed, and these dogs were considered controls. The most frequent age range for dogs with cutaneous neoplasms was 10 to 15 years. Lipoma, adenoma, and mast cell tumor were the most common skin tumor types. CONCLUSIONS AND CLINICAL RELEVANCE-Results supported previously reported data regarding cutaneous neoplasia in dogs but provided updated information on the most common skin tumors and on age and breed distributions.

Prevalência de neoplasmas cutâneos em cães da região metropolitana de Porto Alegre, RS: 1.017 casos (2002-2007)

O objetivo deste trabalho foi realizar um estudo retrospectivo sobre neoplasias cutâneas diagnosticadasem cães. A avaliação foi realizada pela análise dos arquivos diagnósticos do Setor de Patologia Veterinária (SPV) da Universidade Federal do Rio Grande do Sul (UFRGS), Brasil, considerando-se um intervalo de seis anos (2002 a 2007). Neste intervalo, um total de 1.869 (37,3%) amostras de pele canina foram obtidas de 5.016 amostras variadas de tecidos de cães encaminhadas ao SPV. Dentre as amostras cutâneas, 1.002 pertenciam a cães diagnosticadoscom um tipo de neoplasia cutânea e 15 animais apresentaram mais de uma neoplasia de pele, totalizando 1.017 (20,3%) amostras. Os resultados revelaram que 50,5% (514/1017) das neoplasias cutâneas apresentaram origem mesenquimal, 45,1% (459/1017) paraepitelial e 3,9% (40/1017) para melanocítica. Mastocitoma foi o tipo neoplásico cutâneo mais frequente, diagnosticado em 228 casos (22,4%), seguido por carcinoma de células escamosas (7,5%), lipoma (7,3%), adenoma de glândula perianal (7,1%) e tricoblastoma (5,8%). Cocker Spaniel, Boxer, Poodle e Pastor Alemão foram as raças mais representadas em diversos neoplasmas. Os dados obtidos, comparados aos estudos prévios, ressaltam as variáveis raças, idade e sexo, relacionadas a alguns tumores cutâneos e salientam a importância e prevalência dos diferentes tipos de neoplasia cutânea em cães.

Virtual microscopy: an evaluation of its validity and diagnostic performance in routine histologic diagnosis of skin tumors

Digitization of histologic slides is associated with many advantages, and its use in routine diagnosis holds great promise. Nevertheless, few articles evaluate virtual microscopy in routine settings. This study is an evaluation of the validity and diagnostic performance of virtual microscopy in routine histologic diagnosis of skin tumors. Our aim is to investigate whether conventional microscopy of skin tumors can be replaced by virtual microscopy. Ninety-six skin tumors and skin-tumor-like changes were consecutively gathered over a 1-week period. Specimens were routinely processed, and digital slides were captured on Mirax Scan (Carl Zeiss MicroImaging, Göttingen, Germany). Four pathologists evaluated the 96 virtual slides and the associated 96 conventional slides twice with intermediate time intervals of at least 3 weeks. Virtual slides that caused difficulties were reevaluated to identify possible reasons for this. The accuracy was 89.2% for virtual microscopy and 92.7% for conventional microscopy. All κ coefficients expressed very good intra- and interobserver agreement. The sensitivities were 85.7% (78.0%-91.0%) and 92.0% (85.5%-95.7%) for virtual and conventional microscopy, respectively. The difference between the sensitivities was 6.3% (0.8%-12.6%). The subsequent reevaluation showed that virtual slides were as useful as conventional slides when rendering a diagnosis. Differences seen are presumed to be due to the pathologists' lack of experience using the virtual microscope. We conclude that it is feasible to make histologic diagnosis on the skin tumor types represented in this study using virtual microscopy after pathologists have completed a period of training. Larger studies should be conducted to verify whether virtual microscopy can replace conventional microscopy in routine practice.

Clinical and molecular genetics of Carney complex

Carney complex (CNC) is a rare multiple familial neoplasia syndrome that is characterized by multiple types of skin tumors and pigmented lesions, endocrine neoplasms, myxomas and schwannomas and is inherited in an autosomal dominant manner. Clinical and pathologic diagnostic criteria are well established. Over 100 pathogenic variants in the regulatory subunit type 1A (RI-A) of the cAMP-dependent protein kinase (PRKAR1A) have been detected in approximately 60% of CNC patients, most leading to R1A haploinsufficiency. Other CNC-causing genes remain to be identified. Recent studies provided some genotype-phenotype correlations in CNC patients carrying PRKAR1A-inactivating mutations, which provide useful information for genetic counseling and/or prognosis; however, CNC remains a disease with significant clinical heterogeneity. Recent mouse and in vitro studies have shed light into how R1A haploinsufficiency causes tumors. PRKAR1A defects appear to be weak tumorigenic signals for most tissues; Wnt signaling activation and cell cycle dysregulation appear to be important mediators of the tumorigenic effect of a defective R1A.

Growth and progression of melanoma and non‐melanoma skin cancers regulated by ubiquitination

Basal cell carcinomas (BCC), squamous cell carcinoma (SCC), and melanomas are the major types of skin tumors. Despite being skin cancers, the characteristics of each cancer are widely varied. BCCs often do not proliferate rapidly, and rarely metastasize. Squamous cell carcinomas are more malignant and a certain subtype of SCC is highly metastatic. Melanomas are highly proliferative and invasive, and are most frequently metastatic. Ubiquitin and ubiquitin-related proteins post-translationally modify proteins and thereby alter the functions of their target proteins. The ubiquitination process is involved in various physiological responses, including cell growth, cell death, and DNA damage repair. Accumulating evidence suggests that ubiquitin pathways are involved in different types of cancers, including skin cancers. This review describes the major ubiquitin pathways in BCC, SCC, and melanoma. The ubiquitin pathways that are activated among the skin cancers are highly diverse, which might reflect the various characteristics of these three cancer types. Meanwhile, there are also common pathways between BCC, SCC, and melanoma. Therefore, examining the ubiquitin pathways will reveal the mechanisms of these three major skin cancer types and will suggest treatment options.

Ultraviolet light exposure and skin cancer in the city of Arica, Chile

An increase in the amount of solar ultraviolet light that reaches the Earth is considered to be responsible for the worldwide increase in skin cancer. Solar ultraviolet B (UVB) light (290-320 nm) has multiple effects that can be harmful to human beings. The city of Arica in Chile receives high UV levels. This can explain the high prevalence of skin cancer in the Arica population. In the present study, pathological reports of skin cancer were collected from an Arica hospital and retrospectively examined to investigate the possible effects of UV radiation. Among the malignant skin tumor types, basocellular and spinocellular carcinomas were more common in men (44.4 and 16.6%, respectively) than in women (24.9 and 10.7%, respectively). Basocellular carcinoma was observed in individuals 40-79 years of age. The incidence of skin cancer significantly increased (P<0.05) between 2000 and 2006 per 100,000 population. The factor of incidence of skin cancer per 100,000 population significantly increased (P<0.05) between 1980 and 2000 in both genders, but was higher in men (0.79-1.99) than in women (0.63-1.56). The results of the study indicate a steady increase in the incidence of skin cancer in Arica, Chile, most probably due to the high levels of ultraviolet light to which individuals are exposed throughout the year, and the cumulative effect of this type of radiation on the skin.

A retrospective survival analysis of whole brain radiotherapy (WBRT) for brain metastases at Mount Vernon Cancer Centre (MVCC)

2068 Background: The primary purpose of this retrospective study was to determine the survival of patients with brain metastases following WBRT with regards to the influence of tumor type, age &lt; 65 versus ≥ 65 (RPA RTOG prognostic factor) and recency of treatment date. Methods: From treatment records we identified 1,926 patients with brain metastases from solid tumors who were treated with WBRT at MVCC between February 1992 and March 2008. Dates of death were sourced from records at MVCC, the Cancer Registry and GP practices. Results: We obtained dates of death for patients with lung (n=804), breast (n=457), colorectal (n=129), skin (n=119), kidney (n=82), and unknown primary (n=124) cancers. 42 patients were excluded from analysis as their tumor types were unspecified. A heterogeneous group of 169 patients with a variety of other primary tumor types were also excluded from our primary analyses. 22% of the patients died within the first month following WBRT and only 2.4% remained alive at 2 years. Log-rank analysis of age &lt; 65 versus ≥ 65 demonstrated improved survival for the former for the colorectal, lung, and skin tumor types (p = 0.0048, 0.0001, and 0.0456 respectively). This relationship did not reach significance for the breast, unknown primary, and renal cancer groups (p = 0.14, 0.13, and 0.06 respectively). With the exception of colorectal cancer, the analysis of the effect of treatment date on survival did not reveal recent improvements in survival for patients with brain metastases. An improvement in survival was experienced by the colorectal subgroup treated after March 2006 (HR= 0.51 95% CI 0.27- 0.96). Conclusions: Our data validate age as an important prognostic factor for many tumor types with notable exceptions for as yet undetermined reasons. Metastasis to the brain is a late stage feature of colorectal malignancy. The survival of the majority of patients undergoing WBRT for brain metastases is poor and with the possible exception of colorectal cancer, has not improved over the last decade. [Table: see text] [Table: see text]

Expression of Tissue Factor by Eosinophils in Patients with Chronic Urticaria

Background: Although several cases of chronic urticaria (CU) are currently regarded as autoimmune in origin, associated with histamine-releasing autoantibodies, an activation of blood coagulation via tissue factor (TF) and a strong expression of TF in lesional skin have been described. Eosinophils, which are involved in CU skin lesions, have recently been demonstrated as the major source of TF in human blood. We assessed whether eosinophils are the cellular source of TF in CU skin lesions. Methods: Twenty patients with severe CU were studied. Skin biopsy specimens were taken from wheals. The control group consisted of specimens of perilesional normal skin from different types of skin tumours (10) and various skin disorders with non-eosinophilic infiltrates, including leukocytoclastic vasculitis (7), lichen planus (8) and mastocytosis (3). TF expression was evaluated by immunohistochemical methods using an anti-TF monoclonal antibody. Co-localization of TF and eosinophil cationic protein, a classic cell marker of eosinophils, was investigated by double-staining studies using 2 specific monoclonal antibodies in the 4 specimens showing the highest TF reactivity scores. Results: All specimens from patients with CU clearly showed TF expression that was absent in all normal control specimens (p = 0.0001) and in the skin disorders with non-eosinophilic infiltrates (p = 0.001–0.0001). The double-staining experiments for TF and eosinophil cationic protein clearly showed that the TF-positive cells were eosinophils. Conclusions: Eosinophils are the main source of TF in CU lesional skin. This finding highlights the role of these cells in the pathophysiology of CU and might pave the way for new therapeutic strategies.

Independent component analysis of Raman spectra: Application on paraffin-embedded skin biopsies

Raman spectra provide wealthy but complex information about the chemical constituents of biological samples. Digital processing techniques are usually needed to extract the spectra of chemical constituents and their associated concentration profiles. However, spectral signatures may admit transformations from those recorded on pure constituents and these techniques require a priori knowledge of spectra to be estimated. We propose in this study to analyse paraffin-embedded skin biopsies of malignant and benign tumors dedicated to oncology researches by Raman spectroscopy and advanced signal processing methods. We show that the commonly used principal component analysis (PCA) does not give physically interpretable estimators of spectra and associated concentration profiles. Based on a linear model and taking into account the statistical properties of spectra, independent component analysis (ICA) is used to better estimate the spectra of chemical constituents. The estimators of associated concentration profiles are no longer orthogonal and have only positive values, contrary to PCA. ICA allows to model the paraffin by three Raman spectra and provides good estimators of underlying spectra of the human skin, which is of great interest in oncology since the retrieval of spectral features of different types of skin tumors is sufficient for their discrimination.

Skin tumors among employees of a tar refinery: the current data and their implications

Skin tumors and their preliminary stages may be recognized and compensated as an occupational disease only after exposure to soot, raw paraffin, tar, anthracene, pitch or similar substances. The presented study was carried out in one of the world's largest tar refineries and special attention was paid to the dermatological long-term effects and today's relevance of tar-induced skin lesions. The data were generated by means of a standardized questionnaire based on occupational disease records and dermatological reports that have been carried out on a regular basis retrospectively. Among other things, the localization, the number and type of skin tumor, the date of diagnosis and the histological evaluation, where available, were taken into account. In a longitudinal analysis from 1946 to 2002, a total of n = 618 employees were examined. Squamous cell carcinomas n = 393, basal cell carcinomas n = 298, keratoacanthomas n = 194 and melanomas n = 6 were diagnosed. Latency periods for keratoacanthomas (median 29.5 years) and squamous cell carcinomas (median 28.0 years) were almost identical and could possibly imply that the pathomechanisms for both types of skin tumor might be comparable. Of the persons diagnosed, the skin tumors were mainly localized in the head region (n = 1,662). A remarkable divergence in the localization and distribution of the lesions was found when compared to the general population, for example the relative susceptibility of the upper lip (n = 67) compared to the lower lip (n = 31) as well as the less sun-exposed forearms (n = 381) compared to the back of the hand (n = 331), being typically preferred sites of squamous cell carcinomas. Furthermore, a discrepancy between the distribution of premalignant nonmelanoma skin tumors and carcinomas on the back of the nose, which is more exposed to the sun (n = 56) and those in the nostrils (n = 89), which are less exposed to the sun, but are in the act of breathing more exposed to tar, could be found. Tar-induced skin lesions are still of importance nowadays, which is reflected in the incidence of new cases and in the relapses of skin tumors. As a consequence, intensified measures are necessary, in the form of primary and secondary prevention. In view of the high incidence of malignant skin tumors in the general public, it is urgently necessary to take occupational hazards into consideration as well.

Procollagen 1 – a marker of fibroblastic and fibrohistiocytic skin tumors

When dealing with tumors of presumed fibroblastic or fibrohistiocytic origin, immunohistochemistry is traditionally done to exclude a tumor of non-fibroblastic or non-fibrohistiocytic nature, because a reliable marker of fibroblastic or fibrohistiocytic cell origin is still to be introduced. This study investigates whether procollagen 1 is a useful marker of skin tumors composed of cells derived from fibroblasts or fibrohistiocytes. Twenty-nine different types of skin tumors, including tumors composed of spindle cells as well as some additional epithelial and melanocytic tumors, were stained immunohistochemically with antibodies against procollagen 1. The total number of cases tested was 154. Tumors composed of cells of fibroblastic or fibrohistiocytic origin in general showed a high expression of procollagen 1, whereas tumors composed of non-fibroblastic cells in general showed no expression. However, there were a few exceptions, e.g., leiomyosarcoma and desmoplastic melanoma. The study suggests that immunohistochemical staining for procollagen 1 is a valuable marker for skin tumors composed of spindle cells derived from fibroblasts or fibrohistiocytes. However, in cases of spindle cell tumors with a morphology suggesting malignancy, it is recommended to use a panel of antibodies, which besides procollagen 1 includes markers such as S100, CD68, CD34, h-caldesmon, and pancytokeratin.

Photothermal sensitisation as a novel therapeutic approach for tumours: Studies at the cellular and animal level

Irradiation of B78H1 murine amelanotic melanoma cells with 850 nm light emitted from a Ti:sapphire laser, operated in a pulsed mode at high fluence rates and in the presence of Ni(II)-octabutoxy-naphthalocyanine (NiNc), promoted a photothermally sensitised process leading to fast and irreversible cell death. This resulted in the ejection of a consistent mass of cytoplasmic material from the irradiated cells that was detected by scanning electron microscopy. The extensive chemical and mechanical damage was probably caused by the photoinduced generation of an acoustic shock wave. The efficiency of the photoprocess was modulated by intracellular concentration of NiNc and maximally by the formation of aggregated naphthalocyanine clusters in specific subcellular areas. Very similar results were obtained upon irradiation of NiNc-loaded C32 human amelanotic melanoma cells and transformed murine HT-1080 and HaCaT fibroblasts. From these results, photothermal sensitisation appears to be a general phenomenon and preliminary studies with mice bearing subcutaneously transplanted amelanotic melanomas, irradiated with 850 nm light 24 h after intravenous injection of NiNc, suggest that this approach has potential for the therapy of some types of skin tumours.

Chemotherapeutic efficacy of topical celecoxib in a murine model of ultraviolet light B-induced skin cancer.

Over a million nonmelanoma skin cancer cases will be reported in the United States this year alone. Currently the primary form of treatment for these types of skin tumors is excision. However, excision of the initial lesion may not be curative because almost 50% of patients with one nonmelanoma skin cancer lesion develop another tumor within the next 5 yr at the site or adjacent to the site of excision. As with other types of epithelial based cancers, there is mounting evidence for the role of cyclooxygenase-2 (COX-2) and its products, particularly prostaglandin E(2) (PGE(2)), in the development of nonmelanoma skin cancer. To avoid the excision process, the present study was designed to evaluate the possible chemotherapeutic effect of directly treating established tumors with a topical formulation of the specific COX-2 inhibitor celecoxib. Skh/hr hairless mice were irradiated three times per wk for 16 wk to induce tumor formation. The mice were then divided into two groups and treated topically with either 500 microg celecoxib or the vehicle for 6 wk. Our results demonstrated that although topical treatment with celecoxib was not able to induce regression of established tumors, it did prevent new tumor formation after the onset of photocarcinogenesis. Although further studies are warranted, these data suggest that topical celecoxib treatment may prove to be effective in preventing the recurrence of tumors at the site of nonmelanoma skin cancer excision.

Mitochondrial DNA damage in non-melanoma skin cancer.

Mitochondrial DNA (mtDNA) damage, predominantly encompassing point mutations, has been reported in a variety of cancers. Here we present in human skin, the first detailed study of the distribution of multiple forms of mtDNA damage in nonmelanoma skin cancer (NMSC) compared to histologically normal perilesional dermis and epidermis. We present the first entire spectrum of deletions found between different types of skin tumours and perilesional skin. In addition, we provide the first quantitative data for the incidence of the common deletion as well as the first report of specific tandem duplications in tumours from any tissue. Importantly, this work shows that there are clear differences in the distribution of deletions between the tumour and the histologically normal perilesional skin. Furthermore, DNA sequencing of four mutation ‘hotspot’ regions of the mitochondrial genome identified a previously unreported somatic heteroplasmic mutation in an SCC patient. In addition, 81 unreported and reported homoplasmic single base changes were identified in the other NMSC patients. Unlike the distribution of deletions and the heteroplasmic mutation, these homoplasmic mutations were present in both tumour and perilesional skin, which suggests that for some genetic studies the traditional use of histologically normal perilesional skin from NMSC patients may be limited. Currently, it is unclear whether mtDNA damage has a direct link to skin cancer or it may simply reflect an underlying nuclear DNA instability.

Pain caused by photodynamic therapy of skin cancer.

Pain resulting from photodynamic therapy (PDT) of skin cancer was investigated. The study included 69 lesions (60 patients) with different types of skin tumours or precursors. Protoporphyrin IX, which is produced by the topical application of delta-aminolevulinic acid, was used as a photosensitizing agent. Twenty-three of the lesions (19 patients) were examined with a fluorescence imaging system which demarcates the tumour area from the healthy skin and visualizes the contrast between the fluorescence from healthy skin and that from the tumour. EMLA is used on all patients as part of our routine PDT protocol but despite this the major side-effect of PDT is pain during treatment. There is a large variation in pain intensity experienced by the patients, as measured by a visual analogue scale (VAS). Patients with actinic keratoses experienced more pain than those with Bowen's disease or basal cell carcinoma. The mean VAS score was higher when treating lesions located on the head than when treating lesions on the torso or the extremities. Also, treatment of large skin areas resulted in more pain than treatment of small areas, and men experienced more pain than women. The pain experienced by the patients did not correlate with treatment dose, Fitzpatrick skin type, age or fluorescence intensity.

Essential role for Sonic hedgehog during hair follicle morphogenesis.

The hair follicle is a source of epithelial stem cells and site of origin for several types of skin tumors. Although it is clear that follicles arise by way of a series of inductive tissue interactions, identification of the signaling molecules driving this process remains a major challenge in skin biology. In this study we report an obligatory role for the secreted morphogen Sonic hedgehog (Shh) during hair follicle development. Hair germs comprising epidermal placodes and associated dermal condensates were detected in both control and Shh -/- embryos, but progression through subsequent stages of follicle development was blocked in mutant skin. The expression of Gli1 and Ptc1 was reduced in Shh -/- dermal condensates and they failed to evolve into hair follicle papillae, suggesting that the adjacent mesenchyme is a critical target for placode-derived Shh. Despite the profound inhibition of hair follicle morphogenesis, late-stage follicle differentiation markers were detected in Shh -/- skin grafts, as well as cultured vibrissa explants treated with cyclopamine to block Shh signaling. Our findings reveal an essential role for Shh during hair follicle morphogenesis, where it is required for normal advancement beyond the hair germ stage of development.