Fluorescence remission spectroscopy of psoriatic lesions and the effect of topical anthralin therapy

Background  Psoriatic lesions are characterized by induration, scaling and erythema. Erythema is a result of inflammation and increased microvascular blood flow. Anthralin is the strongest topical antipsoriatic drug that causes clearing of psoriatic lesions and temporary remission.
Objective  The objective evaluation of skin perfusion might be a suitable way to gain a better insight in the pathophysiological process of this disease and to evaluate the response to antipsoriatic anthralin therapy.
Methods  We evaluated 21 psoriatic lesions (plaques, patches and pinpoint lesions) including 4 lesions in remission with anthralin induced erythema and 4 controls of healthy, uninvolved skin. We performed the measurements with a combined fluorescence and remission imaging (FRIS). The FRIS sensor is coupled with a touch screen industrial computer. The equipment consists of a white-light halogen lamp (20 W), two VIS-spectrometer modules (Zeiss) for remission detection and references. Imaging is realized by CCD-colour camera module and white light ring-lighting. Fluorescence emission was realized using an ultraviolet LED with a wavelength of 370 nm. The fluorescence detector is a highly sensitive MCS CCD (Zeiss) with an integration time of 2.5 sec.
Results  Spectral remission of psoriatic skin is characterized by a pronounced decrease (60–80%) of the haemoglobin double-peak compared to uninvolved skin. The NADH-fluorescence is diminished in lesional psoriatic skin including anthralin-treated areas with clinical remission.
Conclusions  Vascular perfusion is increased in psoriatic lesions as demonstrated by remission spectroscopy. NADH-fluorescence is reduced in lesional psoriatic skin and in anthralin-induced erythema. FRIS is a suitable tool for objective evaluation of the cutaneous response to antipsoriatic treatment.     

In vivo thickness measurement of basal cell carcinoma and actinic keratosis with optical coherence tomography and 20-MHz ultrasound

Background  Accurate assessment of tumour size is important when planning treatment of nonmelanoma skin cancer (NMSC). Imaging with optical coherence tomography (OCT) has the potential to diagnose and measure depth of NMSC.
Objectives  To compare accuracy of mean tumour thickness measurement in NMSC tumours < 2 mm of depth using OCT and 20-MHz high-frequency ultrasound (HFUS). In addition, OCT morphology of NMSC was studied in OCT images and the influence of histological and colorimetric values on the quality and penetration depth in OCT images was estimated.
Methods  In total, 93 patients were scanned and 34 lesions [23 basal cell carcinoma (BCC) and 11 actinic keratosis (AK) lesions] < 2 mm thick and easily identified in OCT images were studied. OCT and HFUS were compared with biopsies. The influence of skin pigmentation and infiltration analgesia on OCT image quality was studied. Skin colour was measured with a colorimeter.
Results  OCT presented narrower limits of agreement than HFUS. Both methods overestimated thickness but OCT was significantly less biased (0·392 mm vs. 0·713 mm). No relation between OCT penetration depth and skin colour was found.
Conclusions  OCT appears more precise and less biased than HFUS for thickness measurement in AK and BCC lesions < 2 mm, but both OCT and especially HFUS tended to overestimate tumour thickness.     

Non-melanoma skin cancer risk in the Queensland renal transplant population

BACKGROUND: Non-melanoma skin cancer (NMSC) is an important complication of solid organ transplantation, especially in areas of high ultraviolet light exposure. Registry data may underestimate the scale of the problem. OBJECTIVES: A single-observer study of a Queensland renal transplant population was conducted between July 1999 and April 2000 utilizing both cross-sectional and retrospective data. The aims were to determine accurately the risk of NMSC following renal transplantation and compare this with currently available registry data. PATIENTS AND METHODS: A structured interview and full skin examination was completed by 398 renal transplant recipients. Case notes and histology reports were examined for details of previous skin tumours. Independently collected data on 341 subjects from the Australia and New Zealand Dialysis and Transplantation Registry (ANZDATA) were also examined. RESULTS: One hundred and eighty-seven of 361 (51.8%) transplant recipients of Fitzpatrick skin types I-IV had developed 3979 histologically diagnosed NMSCs since first transplantation. The ratio of SCC/BCC was reversed from 1 : 3.7 before transplantation to 2 : 1 after transplantation. NMSC increased with duration of immunosuppression; 29.1%, 52.2%, 72.4% and 82.1% of those immunosuppressed for < 5, 5-10, 10-20 and > 20 years, respectively, had developed at least one tumour. The ANZDATA registry under-recorded the numbers of patients with NMSC by 28.4% and gave no indication of tumour numbers. CONCLUSIONS: NMSC is a greater clinical problem in renal transplant recipients living in subtropical Queensland, Australia, than is shown by currently available registry data. This has implications for the development of prevention and surveillance strategies.     

Viral DNA detection and RAS mutations in actinic keratosis and nonmelanoma skin cancers

Background Actinic keratosis (AK) is a well‐established precancerous skin lesion that has the potential to progress to squamous cell carcinoma (SCC). Basal cell carcinoma (BCC) is a locally aggressive slowly growing tumour that rarely metastasizes. A number of viruses have been proposed to play a role in the development of nonmelanoma skin cancers (NMSC), but the most plausible evidence to date suggests that cutaneous human papillomavirus (HPV) is the key instigating factor. Objectives To evaluate the prevalence of HPV, cytomegalovirus (CMV), herpes simplex virus (HSV) and Epstein–Barr virus (EBV) and investigate their relationship with the presence of RAS gene mutations in cutaneous lesions obtained from nonimmunosuppressed patients. Methods HPV, CMV, HSV and EBV detection was performed using polymerase chain reaction (PCR) in skin biopsies (26 AK, 12 SCC and 15 BCC samples) that were collected from immunocompetent patients. The RAS mutation incidence was also investigated in all cutaneous lesions by use of PCR/restriction fragment length polymorphism and direct DNA sequencing. Results Seventeen out of 53 (32%) skin lesions were found to be positive for HPV DNA. The highest incidences of HPV infection were five of 15 (33%) in BCC and four of 12 (33%) in SCC specimens. The HPV incidence was eight of 26 (31%) in AK and eight of 53 (15%) in normal skin tissue. Twelve out of 53 (23%) skin lesions were CMV‐positive. The highest incidence of CMV infection was six of 15 (40%), observed in BCC specimens. The CMV incidence was two of 26 (8%) in AK and four of 12 (33%) in SCC. No normal skin biopsy was found to be positive for CMV. All cutaneous samples were negative for HSV and EBV DNA, as assessed by our PCR‐based assays. Only three samples, one AK (4%), one BCC (6%) and one SCC (8%), were found to carry a G>T transversion at the second position of HRAS codon 12. Both HRAS mutant SCC and BCC biopsies were HPV‐ and CMV‐positive, as well. Conclusions HPV DNA is detected in NMSC, AK and normal skin biopsies. Our results also indicate that CMV is involved in NMSC at higher levels than in premalignant lesions, whereas the virus was not detected in normal skin biopsies. HSV and EBV do not appear to be involved in the pathogenesis of cutaneous lesions. Moreover, we suggest that the HRAS codon 12 mutation is not a very common event in AK or NMSC. Finally, both viral infection and HRAS activation appear to represent independent factors in the aetiology of NMSC, samples of which were obtained from immunocompetent patients.     

Can autofluorescence demarcate basal cell carcinoma from normal skin? A comparison with protoporphyrin IX fluorescence.

Fluorescence detection may help to demarcate skin cancer from normal skin, thus to reduce the potential of incomplete treatment resulting from unawareness of tumour extension in surrounding skin. In this study we evaluated the difference between autofluorescence of basal cell carcinomas (n = 21) and the normal-appearing skin surrounding them. Referring to the difference found, a point-by-point measurement was taken from the tumour lesions outwards to the surrounding skin to locate the differentiation point of autofluorescence on the skin. Protoporphyrin IX fluorescence was measured from the same spots using the same procedure, after the tumours and the surrounding skin had been treated with topical 5-aminolevulinic acid methyl ester cream. The point-by-point measurement enabled us to locate the vanishing point of the protoporphyrin IX peak, which was compared with the differentiation point of autofluorescence to assess the utility of autofluorescence in tumour demarcation. Illuminated by 370 nm light, both the tumour and surrounding skin emitted a fluorescence with peak intensity at 455+/-3 nm. The peak intensity was 53% (18-84%) (median, range) lower in the tumours than in normal skin (p<0.001). In 78% of the measurements, the differentiation point of the autofluorescence was within 3mm of the vanishing point of the protoporphyrin IX peak. Autofluorescence may be used in BCC demarcation.     

Awareness, knowledge and attitudes to basal cell carcinoma and actinic keratoses among the general public within Europe

OBJECTIVE: As the incidence of non-melanoma skin cancer (NMSC) is reported to be increasing in Europe, the objective of this survey was to establish the general population's awareness and knowledge of basal cell carcinoma (BCC) and actinic keratoses (AK) within five European countries. METHODS: A total of 1500 individuals from the United Kingdom, France, Italy, Germany and Spain were randomly selected to participate in the study. In a 10-minute structured telephone interview respondents answered questions on skin cancer and BCC and AK. RESULTS: Overall, 46% of respondents were concerned about skin cancer. Even though the majority of respondents believed there was a correlation between skin cancer and the sun or overexposure to sunlight, nearly a third of the surveyed population rarely or never used sunscreen when outdoors. In general there was a low level of awareness about BCC and AK, with only 22% and 6% of respondents, respectively, being aware of the conditions. CONCLUSION: There is a need to increase the awareness of skin cancer and safe sun practices among the European population.     

Machine-learning classification of non-melanoma skin cancers from image features obtained by optical coherence tomography

Background/purpose: A number of publications have suggested that optical coherence tomography (OCT) has the potential for non-invasive diagnosis of skin cancer. Currently, individual diagnostic features do not appear sufficiently discriminatory. The combined use of several features may however be useful.
Methods: OCT is based on infrared light, photonics and fibre optics. The system used has an axial resolution of 10 μm, lateral 20 μm. We investigated the combined use of several OCT features from basal cell carcinomas (BCC) and actinic keratosis (AK). We studied BCC (41) and AK (37) lesions in 34 consecutive patients. The diagnostic accuracy of the combined features was assessed using a machine-learning tool.
Results: OCT images of normal skin typically exhibit a layered structure, not present in the lesions imaged. BCCs showed dark globules corresponding to basaloid islands and AKs showed white dots and streaks corresponding to hyperkeratosis. Differences in OCT morphology were not sufficient to differentiate BCC from AK by the naked eye. Machine-learning analysis suggests that when a multiplicity of features is used, correct classification accuracies of 73% (AK) and 81% (BCC) are achieved.
Conclusion: The data extracted from individual OCT scans included both quantitative and qualitative measures, and at the current level of resolution, these single factors appear insufficient for diagnosis. Our approach suggests that it may be possible to extract diagnostic data from the overall architecture of the OCT images with a reasonable diagnostic accuracy when used in combination.     

Association of functional gene variants in the regulatory regions of COX-2 gene (PTGS2) with nonmelanoma skin cancer after organ transplantation

BACKGROUND: Overexpression of cyclooxygenase-2 (COX-2), resulting in excessive prostaglandin production, has been observed in human epidermal keratinocytes after ultraviolet B injury, in squamous cell skin carcinoma (SCC), in actinic keratoses, and in the early stages of carcinogenesis in a wide variety of tissues. The dysregulation of COX-2 expression can in part be due to functional changes affecting regulatory elements in the promoter or 3' untranslated region (UTR) of the gene. Two common polymorphisms (-765G-->C, and -1195A-->G) in the promoter region of the COX-2 gene (now PTGS2), and one common polymorphism in the 3' UTR (8473T-->C) have been described, and reported as associated with various malignancies. OBJECTIVES: To determine if common known polymorphisms in the regulatory region of the COX-2 gene (PTGS2) can be associated with nonmelanoma skin cancer (NMSC) predisposition after organ transplantation, to evaluate if cancer risks are associated with specific COX-2 gene (PTGS2) haplotypes containing these polymorphisms, and to identify possible new genetic polymorphisms in the proximal 5' or 3' regulatory regions of the gene associated with disease. METHODS: The frequency of the three polymorphisms was determined in 240 Northern Italian transplant recipient patients (107 cases and 133 controls) with polymerase chain reaction-restriction fragment length polymorphism analysis. The proximal 5' and 3' regulatory regions of the gene were screened by heteroduplex analysis. RESULTS: Stratification by age at transplant and type of tumours [SCC or basal cell carcinoma (BCC)] demonstrated that allele -765C represented a protective factor in BCC cases undergoing transplantation before 50 years of age (CC + CG vs. GG, Fisher exact test P = 0.003). One rare polymorphism, -62C-->G, was detected in the 5' flanking region. The allele frequency of -62G was 0.019, and no difference in genotype between cases and controls was observed. No other variants were found, suggesting that sequence variations in these regions are not likely to contribute to NMSC risk in this population. Haplotype analysis showed that the haplotype containing all major alleles represents a protective factor in patients with SCC undergoing transplantation after 50 years of age [P = 0.009; OR = 0.37 (0.18-0.79)] and that variant -1195A-->G may represent a risk factor in this subgroup of patients [P = 0.01; OR = 4.77 (1.47-16.41)]. Haplotype analysis in patients with BCC revealed that variant -765C might be a protective factor in patients undergoing transplantation before 50 years of age. Variant 8473T-->C, located in the 3' UTR region of the gene, showed no association with NMSC risk after transplantation. CONCLUSIONS: COX-2 common variants -765G-->C and -1195A-->G appear to be associated with risk of NMSC, although in different ways in the SCC and BCC subgroups, indicating that environmental and genetic risk factors may play different roles in the outcome leading to these two phenotypes.     

A community-based study of nucleotide excision repair polymorphisms in relation to the risk of non-melanoma skin cancer

Nucleotide excision repair (NER) is responsible for protecting DNA in skin cells against UVR-induced damage. Using a candidate pathway approach, a matched case-control study nested within a prospective, community-based cohort was carried out to test the hypothesis that single-nucleotide polymorphisms (SNPs) in NER genes are associated with susceptibility to non-melanoma skin cancer (NMSC). Histologically confirmed cases of NMSC (n=900) were matched to controls (n=900) on the basis of age, gender, and skin type. Associations were measured between NMSC and 221 SNPs in 26 NER genes. Using the additive model, two tightly linked functional SNPs in ERCC6 were significantly associated with increased risk of NMSC: rs2228527 (odds ratio (OR) 1.57, 95% confidence interval (CI) 1.20-2.05) and rs2228529 (OR 1.57, 95% CI 1.20-2.05). These associations were confined to basal cell carcinoma (BCC) of the skin (rs2228529, OR 1.78, 95% CI 1.30-2.44; rs2228527, OR 1.78, 95% CI 1.31-2.43). These hypothesis-generating findings suggest that functional variants in ERCC6 may be associated with an increased risk of NMSC that may be specific to BCC.     

Positivity for HLA DR1 is associated with basal cell carcinoma in renal transplant patients in southern Brazil

Background Renal transplant patients have a higher incidence of non‐melanoma skin cancer (NMSC). Previous studies hypothesized that human leukocyte antigen (HLA), especially types DR1, DR4, and DR7, may influence the incidence of these tumors. This study investigates the association between NMSC and the presence of HLA DR1, DR4, and DR7 in renal transplant patients in southern Brazil. Methods In a historical cohort study, 1032 patients who underwent renal transplantation during the period from January 1993 to December 2006 were examined to identify occurrences of NMSC and HLA status prior to transplant. Results Of the 1032 patients examined, 59 (5.71%) developed NMSC (squamous cell carcinoma [SCC]: 2.42%; basal cell carcinoma [BCC]: 1.74%; both: 1.55%). The presence of HLA DR1 was associated with a higher probability of developing any NMSC and particularly with developing BCC (P < 0.05). There was no statistically significant association between the presence of HLA DR4 or DR7 and the occurrence of NMSC in this sample. Conclusions HLA DR1 appears to be associated with the development of BCC, as well as with the higher number of NMSC lesions in renal transplant patients. This study supports the trend to associate the DR1 allele with BCC and not with SCC.     

The Epidemiology of Non-Melanoma Skin Cancer: Who,Why and What Can We Do about It

Non-melanoma skin cancer (NMSC) comprised of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most common cancers in humans in many countries. Sunlight plays a major part in the development of these tumours which appear predominantly on areas of the most frequently exposed skin. The site distribution for BCC and SCC is not the same, with SCC being most common on the sites of very heavy exposure and BCC becoming more common on areas of only moderate exposure, e.g. upper trunk in men and women and lower leg in women. Incidence rates of NMSC, where they are being recorded, show rises over time. Mortality rates, on the other hand, have been dropping most of this century until they have been levelling out recently. The case fatality rate due to SCC appears to be between 1–2%. The malignant transformation rate of actinic keratoses to SCC appears to be very low. Studies on similar populations at different latitudes allow estimates to be made of increases which might occur with increasing exposure to ultraviolet radiation (UVR) over a life time. These have been used to estimate the possible increases in NMSC due to stratospheric ozone depletion. Finally, recent studies on the reduction of existing actinic keratoses and prevention of new ones with regular use of sunscreen augurs well for prevention of NMSC in the future.     

A broad spectrum of human papillomavirus types is present in the skin of Australian patients with non-melanoma skin cancers and solar keratosis

BACKGROUND: Human papillomavirus (HPV) may play a role in the pathogenesis of non-melanoma skin cancer (NMSC) in epidermodysplasia verruciformis (EV) patients, but in the general population no specific HPV types have been associated with these lesions. Objectives To examine the spectrum of HPV types present in the skin and tumours of Australian patients with NMSC or solar keratosis (SK). METHODS: Biopsies from tumours, and cotton swab samples of perilesional skin and buttock skin from each of 59 Australian patients with basal cell carcinoma (BCC), squamous cell carcinoma (SCC) or SK were tested for HPV DNA by polymerase chain reaction (PCR) using HPV consensus (FAP) primers and by type-specific primers for HPV 38 and candidate HPV 92. The identification of HPV type from consensus PCR was performed by sequencing and comparison with GenBank. RESULTS: In total, 49 of 59 (83%) patients harboured HPV DNA, which was detected in 28 of 64 (44%) biopsies, 48 of 64 (75%; P < 0.001) perilesional swabs and 36 of 59 (61%; P = 0.04) buttock swabs. Forty-five different HPV types/putative types were detected: 15 were previously characterized HPV types, 17 were earlier described putative types and 13 were new putative types. In addition, six subtypes and four variants of HPV sequences were identified. HPV types within the B1 group (EV HPV types) were found in 26 of 64 (40%) lesions, 44 of 64 (69%) perilesional swabs and 35 of 59 (59%) buttock swabs. HPV 38 was detected in 23 of 59 (39%) patients, and was found in seven of 16 (43%) SKs, but was less common in SCCs [three of 23 (13%); P = 0.037] and BCCs [four of 25 (16%); P = 0.056]. Candidate HPV 92 was found in seven of 59 (12%) patients. CONCLUSIONS: A broad spectrum of HPV types, the majority from the B1 group, was found in skin of Australian patients with skin tumours. HPV 38 was found significantly more often in SK than in SCC. However, the role of cutaneous HPV infection in the pathogenesis of NMSC remains elusive.     

Glutathione S-transferase and CYP1A1 gene polymorphisms and non-melanoma skin cancer risk in Italian transplanted patients

Solid organ transplant recipients are at higher risk of non-melanoma skin cancer (NMSC), especially basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Genetic alterations in the production of detoxifying enzymes such as glutathione S-transferase (GST) and CYP1A1 may enhance this risk. We investigated the frequency of GST genotypes (GSTM1, GSTM3, GSTT1 and GSTP1) and CYP1A1 in 239 transplant recipients: 107 cases with NMSC and 132 controls free from NMSC matched for type of transplanted organ, duration of transplantation, sex and age. Allele GSTP1*A was associated with a higher risk of NMSC [odds ratio (OR) 1.7 (1.1-2.5); P = 0.017]. Homozygosity for allele GSTP1 Val(105) was lower in cases [OR 0.3 (0.1-0.8); P = 0.012], especially in patients with SCC [OR 0.1 (0.0-0.7); P = 0.012]. A higher risk of BCC was found in patients with GSTM1 null/null [null/null versus A + B, OR 3.1 (1.4-6.8); P = 0.003]. Analysis of allelism and interaction between allelic variants showed significant association between combined GSTM1 and CYP1A1 Val(462) genotypes, where individuals homozygous for the risk allele GSTM1 null and carrying also the allele CYP1A1 Val(462), show a higher risk of developing NMSC [OR 4.5 (1.1-21.4); P = 0.03], especially SCC [OR 6.5 (1.4-34.4); P = 0.01]. GSTP1 polymorphisms are associated with both BCC and SCC risk. GSTM1 polymorphisms seem to be involved in BCC risk, while GSTM1 null/null genotype combined with CYP1A1 allele Val(462) are associated with a higher risk for SCC, indicating that allelism and/or interactions between allelic variants at other loci may also influence the risk of NMSC, particularly SCC.     

Recent trends in incidence of nonmelanoma skin cancers in the East of Scotland, 1992-2003

BACKGROUND: Historically, ascertainment of nonmelanoma skin cancer (NMSC) by cancer registries in the U.K. has been shown to be incomplete in several studies. However, recent evidence suggesting that almost all clinically diagnosed NMSCs are verified histologically, coupled with the increasing availability of electronic histopathology data to cancer registries, raises the possibility that this situation may have improved. OBJECTIVES: To assess recent trends in incidence of the main types of NMSC and carcinoma in situ (CIS) of the skin in Scotland. METHODS: The study was restricted to selected health board areas in the East of Scotland for which pathology data have been used routinely to support cancer registration since the early 1990s. Incident cases of squamous cell carcinoma (SCC) of the skin, CIS of the skin, and first ever basal cell carcinoma (BCC) were extracted from the Scottish Cancer Registry covering the period of diagnosis 1992-2003. Sex-specific, age-standardized and age-specific incidence rates were calculated for four consecutive 3-year periods of diagnosis. Estimated annual percentage changes (EAPCs) in incidence were calculated by Poisson regression modelling, with adjustment for age. The percentage distribution of SCC, BCC and CIS of the skin by anatomical site and sex was calculated for the period of diagnosis 1997-2003. RESULTS: The crude incidence of SCC for the period 1995-97 was 34.7 per 100,000, comparable with the best existing Scottish estimate of 32.2 derived from a prospective survey in Glasgow during March 1995. Age-adjusted rates of SCC, first ever BCC, and CIS of the skin have all increased significantly in both sexes between 1992 and 2003 (all P < 0.001), with EAPCs ranging in magnitude from +1.4% (first ever BCC in males) to +5.1% (CIS in males). The majority of lesions arose on the head and neck area, with the exception of CIS, which in females was more commonly located on the limbs. CONCLUSIONS: Ascertainment of NMSC has probably improved since the advent and use of electronic pathology data. Ongoing increases in age-adjusted incidence, combined with ageing of the population, will have major implications for the clinical workload associated with NMSC for the foreseeable future.     

Malignant tumours and psoriasis: climatotherapy at the Dead Sea

In this retrospective, nation-wide cohort study, the risk of cancer was assessed for 1738 Danish patients with psoriasis subjected to climatotherapy at the Dead Sea during 1972-93, by linkage to the Danish Cancer Registry. The overall risk of cancer in patients treated at the Dead Sea (standardized incidence ratio, SIR = 1.59) was higher than that expected in the general population, owing to an excess risk of non-melanoma skin cancer (NMSC) [SIR = 4.2 for basal cell carcinoma (BCC) and 10.7 for squamous cell carcinoma (SCC)]. In addition, the distribution of NMSC among body sites, age groups and sexes was unusual in those treated at the Dead Sea, favouring NMSC in young individuals and at multiple sites (SIR = 10.7 for BCC and 57.2 for SCC), multiple BCCs being particularly common among young women. Thus, people subjected to climatotherapy at the Dead Sea for psoriasis constitute a high-risk group for NMSC, SCC in particular, but not for malignant diseases in general. The study design precludes conclusions on whether climatotherapy plays a specific part in skin carcinogenesis which is different from other sources of ultraviolet (UV) radiation, as climatotherapy is inevitably confounded by excess UV exposure.     

Multiple nonmelanoma skin cancer in an exposed Australian population

BACKGROUND: Patients with nonmelanoma skin cancer (NMSC) frequently develop multiple skin cancers. The study presents incidence rates and rates of excision of NMSC for a population living in a high-risk environment for skin cancer. METHODS: Between 1997 and 1999 a prospective population-based study collected information on all histologically confirmed NMSCs in Townsville, Australia. RESULTS: Of the 6708 patients recorded with NMSC, 38.5% had multiple lesions. Yearly age-standardized incidence rates (per 100,000 inhabitants) of basal cell carcinoma (BCC) were 1444.8 for men, 942.7 for women, and of squamous cell carcinoma (SCC) were 805.0 for men, and 423.6 for women. Compared to incidence rates, age-standardized rates of lesions of BCC were 2.1 times higher in men, 1.6 times higher in women, and of SCC were 1.8 times higher in men and 1.4 times higher in women. CONCLUSIONS: The occurrence of multiple NMSCs compromises results of short-term studies on incidence. Further discussions on the most appropriate strategies to describe the real burden of NMSC are warranted.     

Risk and protective factors for sporadic basal cell carcinoma: results of a two-centre case-control study in southern Germany. Clinical actinic elastosis may be a protective factor

BACKGROUND: There are very few data regarding sun exposure behaviour of patients with basal cell carcinoma (BCC) in central Europe. OBJECTIVES: A case-control study of patients with sporadic BCC was conducted to assess the risk of occupational and leisure-time sun exposure behaviour, precursor lesions for skin cancer and phenotypic factors on the development of sporadic BCC in Ulm and Dresden, Germany. METHODS: A comparison was made of 213 patients with BCC (128 from Ulm, 85 from Dresden; 103 men and 110 women; median age at diagnosis 69 years) and 411 controls (237 from Ulm, 174 from Dresden; 197 men and 214 women; median age 58 years). Crude odds ratios (ORs) and corresponding 95% confidence intervals for all of 64 possible risk factors revealed strong associations in 33 items. Selection of important risk factors was performed in a multiple logistic regression. RESULTS: For sporadic BCC, an increased risk was shown for persons with actinic cheilitis (OR 7.1), actinic keratosis (OR 2.7) and solar lentigo (OR 2.5). The only phenotypic factor indicating risk of sporadic BCC was hair colour, with a higher risk for red/fair than brown/black hair (OR 4.3). There was an increased risk for persons with BCC in first-degree relatives (OR 5.1) and those with sunburn 20 years before sporadic BCC was diagnosed (OR 3.6). Additionally, occupational ultraviolet (UV) exposure appeared to be a risk factor (OR 2.4). In contrast, clinical actinic elastosis showed a protective effect (OR 0.1). CONCLUSIONS: In contrast to earlier reports, clinical actinic elastosis turned out to be the only protective factor for sporadic BCC. A special relationship between wrinkling and BCC risk could not be shown. For basic research, future work should be aimed at elucidating further the different forms of collagen repair processes after intermittent and/or chronic UV exposure. The data strongly support the recommendation that a change in recreational UV exposure habits in individuals, and sunburn avoidance in particular, are necessary not only because of the increased long-term risk of melanoma, but also because of the risk of other skin cancers such as sporadic BCC.     

Systemic photodynamic therapy with aminolaevulinic acid delays the appearance of ultraviolet-induced skin tumours in mice

BACKGROUND: Photodynamic therapy (PDT) with topical aminolaevulinic acid (ALA) has recently been approved by the US Food and Drug Administration for the treatment of actinic keratoses. OBJECTIVES: To determine whether weekly systemic suberythemogenic ALA-PDT could prevent the appearance of ultraviolet (UV) -induced skin tumours in hairless mice. METHODS: One group of 20 mice received daily UV radiation from FS 20 tubes, and weekly intraperitoneal injections of ALA 40 mg kg(-1), each followed 3 h later by 12 J cm(-2) of white light (ALA-PDT). Control groups consisted of mice exposed only to UV, to UV and ALA without white light, or UV and white light without ALA, as well as untreated mice. RESULTS: The tumour-free survival was significantly longer for mice exposed to daily UV and weekly ALA-PDT as compared with the control groups. Neither the mortality nor the incidence of large skin tumours was higher in the UV/ALA-PDT group than in mice exposed only to UV. In vivo fluorescence spectroscopy showed that the 635-nm fluorescence emission within tumours was lower than in normal skin 3 h after ALA administration. This was also confirmed by quantitative fluorescence microscopy. CONCLUSIONS: Systemic ALA-PDT can delay the appearance of UV-induced skin tumours in mice without increasing mortality or the incidence of large tumours.