EGFR/erB-1, HER2/erB-2, CK7 and LP34 expression in preneoplastic lesions of respiratory epithelium: an immunohistochemical and genetic study

Trabalho final do 6º médico com vista à atribuição do grau de mestre a Joana Espírito Santo apresentado à Faculdade de Medicina da Universidade de CoimbraAn interpretative diagnosis of preneoplastic lesions would have impact in lung cancer early diagnosis and survival together with the study of Erb-B family receptors as they have an important role in lung carcinogenesis. The existence of tirosine kinase inhibitors stresses the 2 importance of studding gene alterations with possible defined implications in patients’ selection for chemoprevention schemes and characterization of carcinogenesis. This study concerns bronchial preneoplastic lesions observed in biopsies as basal cell hyperplasia, squamous metaplasia and dysplasia. Using immunohistochemistry, those lesions were characterized by antibodies applied against LP34 (high weigh molecular cytokeratin), CK7, Chromogranin A, Ki67, p53, C-erbB-2 and EGFR. HER2 and EGFR gene copy number was also evaluated by fluorescent in situ hybridization (FISH) in those lesions. The expected results defined the origin cell for adaptative and preneoplastic lesions. By known experiences and published data, beyond the stem cell, the spectral evolution of bronchial preneoplastic lesions was demonstrated by characterizing basal cells (LP34) and their neoplastic potentiality. Dysplasias showed a higher expression of EGFR, Ki67 and p53 with a stepwise increase with the gravity of the preneoplastic lesions. C-erbB-2 immunohistochemical overexpression is a rare event in preneoplastic lesions. Polyssomy was the main mechanism for EGFR and HER2/neu high gene copy number. HER2 and EGFR will be expected to understand early carcinogenesis as well as increased proliferation index (Ki67)