Molecular characterization and immunohistochemistry of basal cell carcinomas of individuals from Vila Real

• Autor(a) principal: Vieira, Maria João da Silva
• Data de Publicação: 2019
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10773/27273
• topic: Basal cell carcinoma; UV-radiation; BCC histological subtypes; Hedgehog pathway; Gorlin syndrome; TERTp mutations

Basal cell carcinoma (BCC) constitutes the most common malignancy among skin cancer, whose origin is still under debate, with a possible response in stem cells. Although mixed histology is common, there are three main subtypes of BCC (nodular, superficial and infiltrative), which have different histological appearances and different levels of aggressiveness. This type of skin cancer has some risk factors associated, as well as molecular mechanisms which are implicated in BCC development. Tumor suppressor p53, responsible for DNA-damage response, was found to be very frequent in several cancer cell lines, including BCC. Telomerase reverse transcriptase (TERT) is the subunit of telomerase which is responsible for maintaining telomeres length, and mutations in its promoter have been considered a prognostic factor for various types of cancers, including for BCC. The main goal of this thesis is to describe TERT promoter (TERTp) mutations and p53 expression, which could possibly lead to find biomarkers for this pathology. P53 expression was evaluated through immunohistochemistry of 165 lesions from 97 patients. TERTp mutations molecular analysis was also performed in 52 BCCs. Through the histological revision of the lesions we observed a significant association between larger tumors, decreased pigmentation and high frequency of lymphocytic infiltrate, with more aggressive tumors. Tumors with necrotic tissue showed significantly higher expression of p53 expression and tumors with a micronodular pattern presented a higher frequency of TERTp mutations. Taking into account data reported in previous studies, both for p53 expression and for TERTp mutations, we expected to find more positive associations with other characteristics of the studied BCCs, which did not occur. Since the TERTp mutations were not evaluated in the entire series, it would be interesting to complete this study, in order to establish a relationship between the two biomarkers - p53 expression and TERTp mutations - upon including all the cases. Further studies, such as the molecular analysis of p53 and the study of TERT expression in BCC, may be undertaken for a more comprehensive understanding of the role of these biomarkers in this type of skin cancer