Risk of basal cell carcinoma in a randomized clinical trial of aspirin and folic acid for the prevention of colorectal adenomas

Patients with the genetic disorder basal cell naevus syndrome are at risk of developing multiple basal cell carcinomas, a form of skin cancer. Treatment with the non‐steroidal anti‐inflammatory drug called celecoxib appears to reduce the risk. There is some evidence that other non‐steroidal anti‐inflammatory drugs, including aspirin, may slightly reduce the risk of non‐melanoma skin cancers in general. High amounts of folic acid in the diet may be linked to a slightly increased risk of basal cell carcinoma. Adenomas are polyps of the large bowel (colon and rectum) which are often multiple; they can develop into bowel cancer. They can be detected and removed by colonoscopy, which is repeated at regular intervals. Aspirin and folic acid may prevent the recurrence of these adenomas. The authors of this study, based in the United States and Canada, studied over a thousand patients with colorectal adenomas (aged 21‐80) who were participating in a trial of aspirin and folic acid in prevention of further polyps, over a 3‐6 year period. The authors looked at pathology reports to see if there was a different incidence of basal cell carcinoma in patients on aspirin/folic acid or placebo (no treatment). 104 of 958 patients eligible for the study developed basal cell carcinoma. Overall, aspirin and/or folic acid therapy had no significant effect on the development of basal cell carcinoma, although aspirin appeared to reduce the risk of further skin cancers in the small group who had been previously diagnosed with skin cancer. They conclude that the protective effect of aspirin against skin cancer is limited to individuals with a high risk of developing skin cancer.     

光动力疗法治疗18例皮肤肿瘤

目的 观察光动力疗法在不宜行手术治疗的皮肤肿瘤中的疗效.方法 8例光线性角化病、6例鳞状细胞癌、3例Bowen病和1例基底细胞癌患者行氨基酮戊酸光动力治疗.氨基酮戊酸配成20％溶液涂于皮损,4～6h后行635 nm红光照射,能量密度为80～ 100 J/cm2,时间20 min,每周照射1次,共3 ～6次,疗程结束后观察疗效.结果 8例光线性角化病,4例鳞状细胞癌,3例Bowen病得到完全缓解,2例鳞状细胞癌,1例基底细胞癌得到部分缓解.18例患者在治疗结束后1、2、3、6个月随访时皮损均无复发.结论 氨基酮戊酸光动力疗法对于不宜行手术治疗的皮肤肿瘤是一种无创、无明显瘢痕形成的治疗方法.     

Factors associated with nonmelanoma skin cancer following renal transplantation in Queensland,Australia

BACKGROUND: Caucasian renal transplant recipients living in Queensland, Australia, have the highest risk of nonmelanoma skin cancer in the world. OBJECTIVE: To determine clinical and environmental factors associated with posttransplantation nonmelanoma skin cancer in Queensland. METHODS: 361 Caucasian adult recipients completed a structured interview and full skin examination. Skin cancer details were obtained from hospital records. RESULTS: Squamous cell carcinoma was strongly associated with blue or hazel eyes, time resident in a hot climate, and pretransplantation squamous cell carcinoma; tumor numbers were associated with birth in a hot climate, childhood sunburn, pretransplantation actinic keratoses, and smoking. The risk of basal cell carcinoma was strongly associated with acute or intermittent sun exposure during childhood and pretransplantation basal cell carcinoma; numbers were associated with blue or hazel eyes, time spent living in a hot climate, and male gender. CONCLUSION: Clinical and environmental factors can be used to identify recipients at risk of nonmelanoma skin cancer in Queensland.     

Keratinocyte carcinoma in organ transplant recipients

Skin cancer commonly affects people who have received a solid organ transplant (heart, lung, liver and kidney). Transplant patients can get multiple skin cancers, some of which can grow very quickly. The commonest types of skin cancer are basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Immunosuppressant medication is used to prevent rejection of the transplanted organ. This alters the body's immune system, which in turn means that transplant patients are more prone to skin cancers that can grow rapidly. Over the last 20 years, newer immunosuppressants have been introduced which are thought to lessen the risk of skin cancer. Previous studies have shown a lower risk of SCC with the newer medication, but no study to date has looked at BCC rates. This study, from Ireland, aimed to find out if the rate of skin cancer in transplant patients has reduced over the last 20 years, spanning the introduction of newer immunosuppressive medications. The National Cancer Registry of Ireland registers all skin cancers for the Republic of Ireland. The authors looked at the rate of skin cancer in people who received a solid organ transplant and compared this to the rate of skin cancer in the general population. They found that the rate of SCC and BCC in patients who received an organ transplant has significantly reduced over the last two decades. This change in risk of skin cancer coincided with changes in immunosuppressant medication, along with focused education and regular skin cancer screening for transplant recipients.     

Clinical comparison of actinic changes preceding squamous cell carcinoma vs. intraepidermal carcinoma in renal transplant recipients

Intraepidermal carcinoma (IEC) is a type of in situ squamous cell carcinoma (SCC), although progression of IEC is rare. We sought to investigate differences between the actinic skin changes preceding the development of both SCC and IEC. Photographs of 63 skin sites at which either SCC or IEC subsequently developed in 37 renal transplant recipients (RTRs) were examined for features of actinic change. We found that areas of skin with an actinic keratosis (AK) > 1 cm² in size were four times more likely to develop SCC as opposed to IEC (OR = 4.42; 95% CI 1.25–15.60). Skin sites with ≥ 25% of the area affected by AK were again four times more likely to develop SCC than IEC. These results highlight the scale of visible actinic damage required for development of SCC compared with IEC, emphasizing the importance of treating areas of skin with marked visible actinic change to reduce SCC risk in RTRs.     

Seropositivity for human papillomavirus and incidence of subsequent squamous cell and basal cell carcinomas of the skin in patients with a previous nonmelanoma skin cancer

Background Infection with human papillomaviruses (HPVs) is a risk factor for several epithelial cancers, but its relationship with keratinocyte tumours has not yet been established. Objective In this prospective study we investigated the possible role of different HPVs in the incidence of a subsequent nonmelanoma skin cancer (NMSC). Methods One hundred and fifty‐three patients with squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) enrolled in a previous case–control study were re‐contacted, and a follow‐up visit was offered. Demographic and clinical data, date of first NMSC presentation, Fitzpatrick skin type and history of NMSC during the follow‐up period were ascertained. Recurrences and new second cancers were considered together as ‘outcomes’ in time‐to‐event analyses and in Cox proportional hazard models. Results Clinical data were obtained in 107 patients. HPV seropositivity at baseline was strongly associated with the risk of developing a second SCC after 5 years for a number of beta and gamma HPV types. For example, HPV‐24‐seropositive patients with an SCC at baseline had a 4‐fold increased risk of developing a subsequent SCC (hazard ratio 4·35, 95% confidence interval 1·2–15·6, P = 0·024). No association between serological status for any HPV type tested and an increased risk of BCC was found. Conclusions We observed a consistent pattern of a positive association between seropositivity for beta and gamma HPV types and the risk of a subsequent SCC in patients with a previous SCC. Our data corroborate the results of previous case–control studies and may spur further prospective studies on the causal role of HPVs in NMSC.     

Clopidogrel: mechanisms of action and review of the evidence relating to use during skin surgery procedures

Patients who have skin surgery may be taking medication that increases the likelihood of bleeding, such as clopidogrel, aspirin, warfarin, heparin and nonsteroidal anti‐inflammatory drugs (NSAIDS). All of these may increase the risk of perioperative and postoperative bleeding. This article examines the mechanism of action of clopidogrel, current practice, and evidence for or against continuing its use during skin surgery. The mechanisms of action of aspirin, warfarin, heparin and NSAIDS will also be briefly discussed.     

Subsequent cancers after in situ and invasive squamous cell carcinoma of the skin

OBJECTIVES: To compare cancer risks after in situ and invasive squamous cell carcinoma (SCC) of the skin and to determine whether these 2 forms of cancer differ in prognostic significance. PATIENTS: Subsequent events after in situ and invasive SCC were studied in the Swedish Family-Cancer Database, in which cancer data were obtained from the Swedish Cancer Registry from 1958 to 1996. Among 22293 patients with in situ SCC, 3940 had first invasive cancer; among 17637 patients with invasive SCC, 3624 had a second occurrence of cancer. MAIN OUTCOME MEASURE: Standardized incidence ratios (SIRs), ratios of the observed to expected number of cases, served as a measure of relative risk. For overall risks, cases diagnosed within the first year of follow-up were omitted. RESULTS: The median age of onset was 72 to 73 years for in situ and invasive SCC, respectively. Standardized incidence ratios of all cancers were increased after in situ SCC (men-women, 1.5:1.3) and invasive SCC (men-women, 1.9:1.5). The subsequent occurrences of cancer and their SIRs were similar after in situ and invasive SCC, with skin cancer showing the highest SIR of 6.4:10.0. Among discordant cancers, increased SIRs were recorded for melanoma and a group of malignant neoplasms observed in patients with immunosuppression, including lymphoma and oral cancers. Subsequent cancers in the salivary glands and nasal cavity also showed increased SIRs, particularly after invasive SCC. CONCLUSION: Risks of subsequent cancers, including skin cancer, melanoma, and internal cancers, showed similar patterns in patients with in situ and invasive SCC, suggesting that the 2 groups have a similar susceptibility to cancer.     

Human skin cancer stem cells: a tale of mice and men

Carcinomas, cancers of epithelial tissues, are the commonest malignancies and cause the greatest cancer mortality worldwide. Among these, the incidence of keratinocyte-derived non-melanoma skin cancers (NMSC), by far the greatest, is increasing rapidly. Yet despite access to tumor tissue, acceptance of human NMSC as a model carcinoma has been hindered by the lack of a reliable xenograft model. Instead, we have relied on the murine two-step carcinogenesis protocol as a reproducible squamous cell carcinoma (SCC) model, but this differs from their human counterpart in cause, site, genetic basis and biological behaviour. By xeno-engraftment of primary human SCC, we were recently successful in demonstrating the presence of primary human SCC cancer stem cells or tumor-initiating cells. These findings once more align the study human SCC as the archetypal carcinoma model. In this review, we describe the evidence for the existence of tumor-initiating cells, with emphasis on skin cancer, limiting our discussions to primary human cancer studies where possible.     

Primär- und Sekundärprophylaxe von Hauttumoren nach Organtransplantation

Skin cancer constitutes the most frequently reported post-transplant malignancy in solid organ transplant recipients (OTR) worldwide. Whereas the risk for malignant melanoma is only moderately increased, non-melanoma skin cancers (NMSC) seem to thrive on chronic immunosuppression and account for up to 95% of post-transplant cutaneous malignancies. Compared to the general population cutaneous squamous cell carcinoma (SCC) and actinic keratoses (AK) characteristically show even higher incidences than basal cell carcinoma (BCC) and act as an indicator for the development of multiple primary cutaneous neoplasias and locally recurrent cancers (field cancerization). Early diagnosis and therapy of pre-malignant cutaneous lesions is crucial for the secondary prophylaxis of further invasive and highly aggressive skin cancers. High quality interdisciplinary care and prophylactic modalities, including consistent and sufficient UV protection, topical immunmodulatory therapies of UV-damaged skin areas, retinoid chemoprevention as well as tapering immunosuppressive treatment or the selection of immunosuppressants with proposed antiangiogenic properties like mTor-inhibitors may help to reduce the multiplicity of subsequent primary skin cancers in high-risk patients. Apart from the continuous need for educational intervention of OTR in the primary prophylaxis of post-transplant skin cancers, dermatologic care occupies a central position within the field of transplantation medicine in terms of pre- and post-transplanation dermatologic evaluation and therapy as well as the implication of timely and effective secondary preventive approaches in the management of this high-risk patient population.     

The role of HPV in keratinocyte skin cancer development: A systematic review

Keratinocyte skin cancers are the most frequent malignancy, accounting for approximately 30% of all cancers. Although beta genus HPV are the main etiologic agents for squamous cell carcinoma development in patients with epidermodysplasia verruciformis and organ transplant recipients, their role in non-melanoma skin cancer (NMSC) progression in the general population remains controversial. The aim of our review is to summarize current scientific data and to systematically analyse evidence regarding the role of HPV in keratinocyte skin cancers. A total of 2284 patients were included, of which 724 with actinic keratoses, 290 with Bowen's disease, 949 with cutaneous squamous cell carcinomas and 321 with keratoacanthomas. In the case of actinic keratoses, the majority were positive for beta (n = 372, 58.49%) and gamma HPV (n = 256, 40.25%) and only a few (n = 6, 0.94%) were positive for alpha subtypes. Similarly, most of the cutaneous squamous cell carcinomas were positive for beta (n = 248, 55.98%) and gamma HPV (n = 172, 33.82%) and 23 cases (2.42%) were positive for alpha subtypes. Bowen's disease lesions were mostly positive for beta (n = 43, 55.84%) and alpha HPV (n = 30, 38.96%), in contrast to the gamma genus (n = 4, 5.19%). Keratoacanthomas showed a high distribution among beta genus (n = 79, 50.31%) and an equal proportion between alpha (n = 39, 24.84%) and gamma (n = 39, 24.84%) genera. Studies published so far identifying HPV in keratinocyte skin cancers reflect the difference in detection methods rather than a type-specific tendency towards either actinic keratoses, Bowen's disease, squamous cell carcinoma or keratoacanthoma. On the other hand, recent evidence regarding the role of HPV vaccination in patients with non-melanoma skin cancer brings into perspective the idea of a beta-HPV vaccine or a combined alpha and beta-HPV vaccine that could be used as an adjuvant treatment measure in patients with recalcitrant non-melanoma skin cancer.     

Skin cancer in a Queensland population

In the present study we have estimated the current prevalence of actinic skin disease in young and middle-aged adults in Queensland, Australia by surveying a representative community. It was found that 4.6% of persons aged 20 to 69 years had skin cancer, mostly basal cell carcinoma, and 40% had solar keratoses. The age distribution and site distribution of actinic lesions in this population were not as classically described; persons below age 40 years exhibited substantial sun-related skin damage, and a large proportion of actinic lesions occurred on sites other than the head, backs, of hands, or forearms. Allowing for age and sex, the strongest risk factors for skin cancer and solar keratoses were fair skin, as assessed by a dermatologist, and clinical signs of solar damage such as solar lentigines, facial telangiectasia, and actinic elastosis of the neck. Associations with self-reported tendencies toward sunburn, frequent painful sunburns, occupational sun exposure, and a previous history of skin cancer were confirmed.     

Body-site distribution of skin cancer, pre-malignant and common benign pigmented lesions excised in general practice

Background Concern about skin cancer is a common reason for people from predominantly fair‐skinned populations to present to primary care doctors. Objectives To examine the frequency and body‐site distribution of malignant, pre‐malignant and benign pigmented skin lesions excised in primary care. Methods This prospective study conducted in Queensland, Australia, included 154 primary care doctors. For all excised or biopsied lesions, doctors recorded the patient’s age and sex, body site, level of patient pressure to excise, and the clinical diagnosis. Histological confirmation was obtained through pathology laboratories. Results Of 9650 skin lesions, 57·7% were excised in males and 75·0% excised in patients ≥ 50 years. The most common diagnoses were basal cell carcinoma (BCC) (35·1%) and squamous cell carcinoma (SCC) (19·7%). Compared with the whole body, the highest densities for SCC, BCC and actinic keratoses were observed on chronically sun‐exposed areas of the body including the face in males and females, the scalp and ears in males, and the hands in females. The density of BCC was also high on intermittently or rarely exposed body sites. Females, younger patients and patients with melanocytic naevi were significantly more likely to exert moderate/high levels of pressure on the doctor to excise. Conclusions More than half the excised lesions were skin cancer, which mostly occurred on the more chronically sun‐exposed areas of the body. Information on the type and body‐site distribution of skin lesions can aid in the diagnosis and planned management of skin cancer and other skin lesions commonly presented in primary care.     

皮肤鳞状细胞癌和光线性角化病的免疫组化研究

目的探讨光线性角化病[AK]的性质以及其与鳞状细胞癌(SCC)的关系。方法用免疫组化的方法研究了桥粒芯糖蛋白1(D sg1)和E-钙黏着蛋白(Ecad)在鳞状细胞癌和光线性角化病中的表达。结果与正常人皮肤相比桥粒芯糖蛋白1和E-钙黏着蛋白在光线性角化病中的表达减弱,在鳞状细胞癌中的表达显著减弱或完全消失,但两者在角化不良细胞处的表达非常相似。结论光线性角化病应及早治疗以阻止其发展。     

The burden of cutaneous adnexal carcinomas and the risk of associated squamous cell carcinoma: a population-based study

Globally, skin cancer is one of most common forms of cancer. There are several types, the most common being non-melanoma skin cancer, which includes basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). In the UK, more than 100,000 new cases of non-melanoma skin cancers are diagnosed every year. Cutaneous adnexal carcinomas (CACs) are rare tumors which are often difficult to diagnose. This study, from Italy, aimed to evaluate how the number of CACs in the population has changed over time and identify if there is a link between CAC presence and the risk of developing SCC. Data was analysed from the Tuscany Cancer Registry (TCR) from a 25-year time period between 1985 and 2010. 242 patients with CACs were identified from this period with the number of patients with CACs growing from 2.5 per million in 1985-87 to 19 per million in 2009-10. Between 1997 and 2010, CAC presence in the population increased by 159%. It was also found that patients with CAC were 34 times more likely to develop SCC later in life than those without CAC, suggesting that this is a significant risk factor. The authors of this study predict that the number of patients with CAC is likely to continue to increase, due to an ageing population. This combined with the link between CAC and SCC highlights the need to improve diagnosis of CACs in the future.     

Multiple skin cancers in patients with mycosis fungoides after long‐term ultraviolet phototherapy

Phototherapy is a useful noninvasive therapy, but it can induce cutaneous malignant tumours, including squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). We report on a 79‐year‐old man who had long‐standing mycosis fungoides for 40 years, which had been treated with psoralen ultraviolet A therapy for 37 years at a dose of approximately 5000 J/cm². Approximately 6 years before presentation, numerous types of cutaneous malignancies, including actinic keratosis, BCC and SCC, had begun to develop all over the patient's body. We hypothesized that he was experiencing a pathogenesis similar to patients with xeroderma pigmentosum (XP), and we therefore assessed his DNA repair capacity. Based on these investigations, the patient was eventually diagnosed as non‐XP, even though we detected that his DNA repair capacity was slightly lower than that of normal controls, which may have led to the skin cancers. We speculate that multiple skin malignancies can be induced by long‐term phototherapy in patients with slightly impaired DNA repair capacity.     

A population-based study of skin cancer incidence and prevalence in renal transplant recipients

BACKGROUND: Cancers occurring following solid organ transplantation are a rapidly growing public health concern. Defining the extent of the problem has been limited by surveillance systems with incomplete registration of cases and the paucity of reliable national incidence data. OBJECTIVES: To determine the incidence of all cancers following renal transplantation and to make a detailed examination of trends and patterns associated with postrenal transplant skin cancers. METHODS: Integration of data from the national renal transplant database and the national cancer registry in Ireland enabled accurate determination of the number of renal transplant recipients (RTRs) with skin cancers and other malignancies in the time period 1 January 1994 to 31 December 2001. RESULTS: We demonstrated a biphasic increase in skin cancer incidence following renal transplantation, determined by the age at transplantation. There was a steady increase in risk for older RTRs (age 50+ years) from year 2 post-transplant, whereas the increased risk in younger RTRs (age < 50 years) occurred later but much more significantly, reaching 200 times the risk for an age-matched nontransplanted population by year 6 post-transplant. The number of nonmelanoma skin cancers (NMSCs) registered in RTRs accounted for 1% of all NMSCs registered nationally over the study period. The standardized incidence rates for invasive NMSC (33-fold increase) and in situ carcinoma of the skin (65-fold increase) were significantly increased (P < 0.05). The risk for invasive squamous cell carcinoma (SCC) was increased 82-fold compared with the nontransplanted population. Male RTRs were at particular risk of invasive SCC at sun-exposed sites such as the scalp and the external ear. Risk of malignant melanoma and Kaposi sarcoma were also increased relative to the nontransplanted population. CONCLUSIONS: This comprehensive national study illustrates how rates of skin cancer in Irish RTRs have influenced the national incidence of skin cancer. The high incidence of SCC, basal cell carcinoma and Bowen's disease in the early post-transplant period for older patients and the cumulative risk in younger patients with increased duration of transplantation highlight the importance of implementing early and continued cancer surveillance regimens post-transplant.     

Cancer/testis antigen MAGE-A4 expression pattern differs in epithelial skin tumors of organ-transplant recipients and immunocompetent patients

BACKGROUND: Lifetime risk for squamous cell carcinoma (SCC) of the skin is 1:30. Risk in organ-transplant recipients (OTR) is increased over 60-fold through long-term drug-induced immunosuppression. MAGE family-derived peptides are cancer/testis antigens recognized by specific CD8(+) T cells and employed for immunotherapy. We were interested in the frequency and distribution of MAGE-A4 in epithelial skin tumors of OTR and immunocompetent patients. METHODS: mAb 57B predominantly recognizing MAGE-A4 was used to stain 119 formalin-fixed, paraffin-embedded epithelial skin tumors (actinic keratosis, bowenoid actinic keratosis, Bowen's disease, and SCC; n = 17, 25, 61, 16, respectively) in immunocompetent patients (n = 84) and OTR (n = 35). RESULTS: All four epithelial skin tumors showed comparable immunoreactivity ranging from (25-71%, p = 0.361). Scattered immunoexpression pattern was more frequent in OTR (p = 0.025). SCC showed polarized immunoreactivity basally (p = 0.002). CONCLUSION: MAGE-A4 was expressed in a large part of epithelial skin tumors with predominantly scattered immunoexpression pattern in OTR. The difference in immunoexpression pattern for immune status was limited, suggesting important non-immunosuppressor-mediated mechanisms for increased skin carcinogenesis in OTR. mAb 57B may be a helpful tool for immunohistochemistry and micrographic surgery using formalin-fixed paraffin-embedded tissue.     

Malignant tumours and psoriasis: a follow-up study

This nationwide follow-up study concerns the pattern of malignant tumours in a cohort of patients with psoriasis, at an average of 9.3 years after discharge from hospital. The study confirms that the significantly increased risk of cancer in these patients, amounting to 1.4 times that in the general population, is mainly due to cancer of the skin and lung in both sexes and cancer of the pharynx and larynx in men. Non-melanoma skin cancer is the most common malignancy, occurring in 196 of 795 patients with cancer: standardized incidence ratio (SIR, the ratio of observed to expected cancers) 2.4 for men and 2.6 for women. This means an overall lifetime risk (up to the age of 75 years) of 14.1%. In particular, squamous cell carcinoma (SCC) by itself (n = 45, SIR 3.9 for men and 4.7 for women), cancer in multiple sites (SIR 5.9 for basal cell carcinoma (BCC) and 11.7 for (SCC) and SCC on the lower extremities (SIR 18.0) are frequent. Women run the highest risk of BCC in the age range 20-40 years, while men in the age range 30-60 years run a particularly high risk of SCC. When monitoring patients extensively treated for psoriasis, this aberrant pattern of cancer should be taken into account.     

T‐cadherin loss induces an invasive phenotype in human keratinocytes and squamous cell carcinoma (SCC) cells in vitro and is associated with malignant transformation of cutaneous SCC in vivo

Background Cadherins play important roles in controlling keratinocyte growth, differentiation and survival. Atypical glycosylphosphatidylinositol‐anchored T‐cadherin (T‐cad) is highly expressed in the basal keratinocyte layer of skin. The role of T‐cad in keratinocyte biology and pathology is unclear. Objectives To define the role of T‐cad in the pathogenesis of cutaneous squamous cell carcinoma (SCC) through gain‐of‐function and loss‐of‐function studies in vitro and through examination of T‐cad expression patterns in human cutaneous SCC specimens in relation to histological classification of degree of tumour differentiation. Methods In vitro studies employed lentiviral‐mediated overexpression/silencing of T‐cad in normal human keratinocyte (HaCaT) and SCC (A431) cell lines, monolayer and multicellular spheroid culture models, cell morphology analyses and assays of random motility and invasion. Immunohistochemistry was performed on skin specimens from patients with actinic keratosis, Bowen disease or SCC. Results In vitro, silencing of T‐cad induced a morphologically elongated and disorganized cell phenotype, increased random motility and markedly enhanced invasive potential. Overexpression of T‐cad induced a morphologically spread and compact cell phenotype and blunted invasive potential. In vivo, regional loss of T‐cad expression was more frequent and prominent in SCC classified as moderately‐to‐poorly differentiated than in SCC classified as well differentiated. However, in both categories aberrant and/or absence of T‐cad expression was associated with histological features of a potentially more malignant and invasive phenotype of cutaneous SCC. Conclusions T‐cad is a controlling determinant of SCC phenotype and invasive behaviour and its loss is associated with the process of malignant transformation from noninvasive to invasive SCC.