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Notes: Background Renal transplant recipients have an increased incidence of skin cancers, which may be multiple and aggressive.Objectives The purpose of this study was to examine the chemoprophylactic effects of low-dose etretinate (0.3 mg/kg/day) on skin cancer development in renal transplant recipients and to monitor retinoid toxic effects at this dose.Methods All skin lesions were counted and photographed prior to therapy with etretinate. Patients were assessed at monthly intervals for new skin lesions and for retinoid toxicity.Results Eleven renal transplant recipients participated. There was a significant reduction in the number of skin cancers which occurred during etretinate therapy compared with pre-treatment for 3 and 6 months of treatment, and a trend towards fewer skin cancers in the 12 and 18 month treatment periods. Side-effects were well-tolerated and no significant biochemical effects were observed.Conclusion Low dose etretinate is safe, well-tolerated and partially effective in chemoprophylaxis of skin cancer in renal transplant recipients.

Notes: Langerhans cells (LC) are a unique population of antigen-presenting cells in the epidermis which may play a role in the defense mechanisms against skin tumors. Renal transplant recipients (RTRs) have a significantly increased incidence of premalignant and malignant skin lesions. Langerhans cells, which are important for local immune surveillance, may be depleted or downregulated in skin neoplasms of RTRs, facilitating their growth. We investigated the Langerhans cell densities in 29 squamous cell carcinomas (SCCs), five basal cell carcinomas (BCCs), four Bowen's disease, eight dysplastic lesions (actinic keratoses), and three viral warts from 15 RTRs and compared these to the Langerhans cell densities in normal control skin. Eleven RTRs were receiving low-dose etretinate as chemoprophylaxis for recurrent skin cancer and the effect of low-dose retinoid therapy on Langerhans cell densities in SCCs from these patients was also assessed. Langerhans cells in frozen tissue sections were stained with the anti-human Leu-6 monoclonal antibody.〈section xml:id="abs1-3"〉〈title type="main"〉ResultsThere was no significant difference in LC numbers between normal skin from RTRs and normal skin from non-immunosuppressed individuals. There was a statistically significant reduction in LC/mm2 and LC/1000 K (keratinocytes) for SCC, BCC, dysplastic lesions and viral warts compared with normal skin (P 〈 0.001, P 〈 0.01, P 〈 0.001, P 〈 0.05, respectively). There was a trend for an increase in Langerhans cell density in SCCs which developed during etretinate therapy compared with pre-etretinate but the difference was not statistically significant.〈section xml:id="abs1-4"〉〈title type="main"〉ConclusionsIn this study of RTRs, a significant reduction in Langerhans cell densities was observed in SCCs, BCCs and dysplastic lesions compared with normal skin. A reduction in Langerhans cell density in viral warts from RTRs was also observed. A working hypothesis may include a multifactorial etiology for this reduction in Langerhans cell densities. It is possible that human papilloma virus (HPV) infection, by reducing intraepidermal Langerhans cell density, may decrease local immune surveillance and facilitate the development of skin cancers. Ultraviolet radiation and immune suppression may also play a role. The marked depletion of Langerhans cells in skin cancers, precursor lesions and viral warts suggests a central role for Langerhans cells in skin cancer promotion in RTRs.

Notes: The prognostic significance of c-erbB-2 expression was studied in paraffin wax embedded colorectal cancer tissue using a monoclonal antibody. One hundred and sixty-four patients with Dukes' B disease were studied. Membranous staining was not detected in any case. Cytoplasmic c-erbB-2 staining was seen in 55 cancers (33.5%). Cytoplasmic taining was unrelated to patient age (P= 0.31), sex (P= 0.69), tumour site (P= 0.69), size (P= 0.57), histological grade (P= 0.42) or ploidy status (P= 0.21) but was found more frequently in obstructing cancers (P= 0.03). Mean follow up of the patient population was 6.3 years. Five-year-survival estimated by the Kaplan-Meier life-table method was 47% for those with cytoplasmic c-erbB-2 staining and 77% for those without (log rank analysis; P? 0.0001). Stepwise regression analysis identified c-erbB-2 staining (relative risk, 2.51; P= 0.0005) and bowel obstruction (relative risk, 1.99; P= 0.015) as independent predictors of survival. It is suggested that cytoplasmic c-erbB-2 expression may provide a useful marker of tumour behaviour in Dukes' B colorectal cancer.