Expression of heparanase in basal cell carcinoma and squamous cell carcinoma

Abstract: Background: Heparanase is an enzyme that cleaves heparan sulfate chains. Oligosaccharides generated by heparanase induce tumor progression. Basal cell carcinoma and squamous cell carcinoma comprise types of nonmelanoma skin cancer. Objectives: Evaluate the glycosaminoglycans profile and expression of heparanase in two human cell lines established in culture, immortalized skin keratinocyte (HaCaT) and squamous cell carcinoma (A431) and also investigate the expression of heparanase in basal cell carcinoma, squamous cell carcinoma and eyelid skin of individuals not affected by the disease (control). Methods: Glycosaminoglycans were quantified by electrophoresis and indirect ELISA method. The heparanase expression was analyzed by quantitative RT-PCR (qRTPCR). Results: The A431 strain showed significant increase in the sulfated glycosaminoglycans, increased heparanase expression and decreased hyaluronic acid, comparing to the HaCaT lineage. The mRNA expression of heparanase was significantly higher in Basal cell carcinoma and squamous cell carcinoma compared with control skin samples. It was also observed increased heparanase expression in squamous cell carcinoma compared to the Basal cell carcinoma. Conclusion: The glycosaminoglycans profile, as well as heparanase expression are different between HaCaT and A431 cell lines. The increased expression of heparanase in Basal cell carcinoma and squamous cell carcinoma suggests that this enzyme could be a marker for the diagnosis of such types of non-melanoma cancers, and may be useful as a target molecule for future alternative treatment.

Expressão de metaloproteinases de matriz e de seus inibidores teciduais em carcinomas basocelulares / Expression of matrix metalloproteinasis and their tissue inhibitors in basal cell carcinoma

INTRODUÇÃO: Aproximadamente 80 por cento das neoplasias malignas de pele não-melanomas são carcinomas basocelulares (CBC). Apesar das raras metástases, esses tumores são localmente agressivos. As metaloproteinases de matriz (MMPs), especialmente as MMP-2 e 9, são importantes no processo de invasão. Em contrapartida, os inibidores teciduais das MMPs (TIMPs) têm como principal função a inibição dessas enzimas. OBJETIVO: Investigar a associação de variáveis clinicopatológicas de pacientes portadores de CBC com a expressão de MMP-2, MMP-9, TIMP-1 e TIMP-2. MATERIAL E MÉTODOS: Foram selecionados 31 casos de CBC, sendo então obtidos, retrospectivamente, os dados referentes a idade, sexo e tamanho da lesão. Cortes histológicos das lesões foram submetidos a reação imuno-histoquímica pela técnica estreptavidina-biotina-peroxidase para detecção dos antígenos de interesse. Índices de imunomarcação foram construídos e comparados com os dados previamente obtidos. RESULTADOS: Observou-se correlação significativa entre idade e tamanho da lesão (R = 0,532; p = 0,008). Não foram observadas correlações significativas entre as outras variáveis e a expressão imuno-histoquímica dos antígenos de interesse. CONCLUSÃO: A expressão das metaloproteinases e de seus inibidores teciduais não parece ser influenciada pelos parâmetros investigados. Estudos adicionais são necessários para melhor compreensão de sua associação com o comportamento biológico do CBC.

INTRODUCTION: Approximately 80 percent of non-melanoma skin neoplasias are basal cell carcinomas (BCC). Although metastasis is rare, BBC carcinomas are locally aggressive tumors. Matrix metalloproteinases (MMPs), mainly MMP-2 and MMP-9, play an important role on the invasion process. On the other hand, tissue inhibitors of MMPs (TIMPs) have the main function of inhibiting these enzymes. OBJECTIVE: To investigate the association of clinical-pathological variables of BCC patients with the expression of MMP-2 and MMP-9, TIMP-1 and TIMP-2. Methods: Thirty-one BCC cases were selected. Gender, age of the patients and size of the lesions were obtained retrospectively. Histological cuts of the lesions were exposed to immunohistochemistry reaction by use of the streptavidine-biotin peroxidase technique in order to detect antigens. Immunomarking parameters were established and compared with previous data. RESULTS: A significant correlation between age and size of the lesion was observed (R = 0.532; p = 0.008). No significant correlations between other variables and immunohistochemical expression of antigens were observed. CONCLUSION: The expression of MMPs and TIMPs does not seem to be influenced by the parameters investigated in this work. Additional studies should be made to better understand its association with the biological behavior of basal cell carcinomas.

Influence of the glutathione s-transferase gene polymorphisms on the susceptibility to basal cell skin carcinoma

Background: The identification of groups at high risk is fundamental to determine preventive strategies for skin cancer. Destructive reactive oxygen species produced by UVA or chemical carcinogens are metabolized by a series of enzymes. Polymorphisms of genes encoding for these enzymes may produce defective proteins with a diminished ability to detoxify a wide range of carcinogens. Aims: To ascertain the influence and potential interactions of several polymorphisms of genes encoding four important antioxidant GST enzymes in the susceptibility to cancer among Brazilians. Material and methods: We compared the genotypes of Glutathione S-Transferase mu, theta, pi and omega (GSTM1, GSTT1, GSTP1 and GSTO2) in a group of 102 patients with skin lesions and 124 controls. Results: Patients with Basal Cell Skin Carcinoma (BCC) presented the combined GSTM1-GSTT1+ genotype more frequently (49.1 percent) than controls (29.8 percent) (Fisher test; p =0.04), conferring a 2.273 (Odds Ratio; 95 percent CI =1.199-4.308) higher risk for BCC. We were not able to find any other association between genotypes or between any genotype and the patients' clinical features. Conclusions: The GST profile may help identify Brazilian individuals at higher risk for BCC.

Antecedentes: La identificación de grupos en riesgo elevado es fundamental en la determinación de las estrategias preventivas para el cáncer de la piel, el maligno humano más común. Las especies reactivas destructivas del oxígeno producidas por UVA o los agentes carcinógenos químicos son metabolizadas por una serie de enzimas. Los polimorfismos de los genes que codifican para estas enzimas pueden producir las enzimas defectuosas con una capacidad disminuida de desintoxicar una amplia gama de agentes carcinógenos. Objetivo: Este estudio fue diseñado para comprobar las interacciones de la influencia y del potencial de varios polimorfismos de los genes que codificaban 4 enzimas importantes del antioxidante GST en la susceptibilidad al cáncer entre brasileños. Métodos: Comparamos los genotipos del mu del S-Transferase del Glutathione, de la theta, de pi y de Omega (GSTM1, GSTT1, GSTP1 y GSTO2) en un grupo de 102 lesiones de piel y de 124 controles. Resultados: Los pacientes con el carcinoma basocelular (BCC) presentaron el genotipo combinado de GSTM1-GSTT1+ más frecuente (49,1 por ciento) que los controles (29,8 por ciento) (Fisher test; p =0,04), confiriendo 2.273 (Odds Ratio 95 por ciento CI =1.199-4.308) un riesgo más alto para BCC. No encontramos ninguna otra asociación entre los genotipos o entre ningún genotipo y características clínicas de los pacientes. Conclusiones: Sugerimos que el perfil de GST pueda ayudar a identificar a individuos brasileños en un riesgo más alto para BCC.

Estudio "in situ" de las poblaciones de celulas mononucleares en carcinomas de piel / \"In situ\" study of mononuclear cell populations in skin carcinoma

Se realizo un estudio inmunohistologico con anticuerpos monoclonales IOR y se identificaron las poblaciones de celulas mononucleares presentes en el infiltrado reaccional de los carcinomas basocelular y epidermoide de piel. Se comparo la composicion celular del infiltrado reacional entre estos carcinomas, se encontraron diferencias significativas en el comportamiento de lapoblacion de linfocitos T CD6+ y de monocitos y macrofagos. Por los resultados obtenidos se explica como pudieran influir en el comportamiento biologico de estos tumores

Expression of the nucleoside diphosphate kinase in human skin cancers: an immunohistochemical study

Expression of nucleoside diphosphate(NDP) kinase, which is homologous to the nm23 gene product in a variety of species, has been found to be inversely associated with metastatic potential. However, the relationship remains controversial according to the tumor cell types and experimental system, with conflicting results from different research groups. In order to determine whether NDP kinase expression serves as a marker for metastatic potential in human skin cancer, we assessed the levels of NDP kinase expression in 9 keratoacanthomas (KAs), 26 squamous cell carcinomas (SCCs), and 25 basal cell carcinomas (BCCs) using immunohistochemistry. The expression of NDP kinase was intense in KA and SCC compared with BCC. However, the difference of NDP kinase expression between KA and SCC was not statistically significant. And there was no statistically significant difference in NDP kinase expression between SCC with metastasis and SCC without metastasis. Our results contradict the hypothesis concerning the possible role of nm23 gene as a metastatic suppressor gene in human skin cancer. The mechanism of overexpression in various tumor cell types and its biological significance in cutaneous carcinogenesis remain to be determined.