title: EGFR/erB-1, HER2/erB-2, CK7, LP34, Ki67 and P53 expression in preneoplastic lesions of bronchial epithelium: an immunohistochemical and genetic study.
abstract: A prognostic interpretation of preneoplastic lesions would have impact in bronchial carcinoma early diagnosis and through the study of Erb-B family receptors as they have an important role in lung carcinogenesis. The existence of drugs as tyrosine kinase inhibitors stressed the importance of studying gene alterations for selected chemoprevention schemes and characterization of carcinogenesis. Bronchial preneoplastic lesions were characterized by immunohistochemistry using the antibodies 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 in those lesions. The expected results defined the origin cell for basal cell hyperplasia and squamous metaplasia as adaptative lesions and dysplasia. 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 respective grading. C-erbB-2 immunohistochemical overexpression was a rare event in preneoplastic lesions. Polysomy was the main mechanism for EGFR and HER2/neu higher gene copy number and together with increased proliferation index (Ki67) will account to preview bronchial carcinogenesis.
authors.affiliation: IAP-FMUC-Institute of Pathology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: Vítor
authors.initials: V
authors.lastname: Sousa
authors.forename: Joana
authors.initials: J
authors.lastname: Espírito Santo
authors.forename: Maria
authors.initials: M
authors.lastname: Silva
authors.forename: Teresa
authors.initials: T
authors.lastname: Cabral
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Alarcão
authors.forename: Ana
authors.initials: A
authors.lastname: Gomes
authors.forename: Patrícia
authors.initials: P
authors.lastname: Couceiro
authors.forename: Lina
authors.initials: L
authors.lastname: Carvalho
mesh_terms: D001980:Bronchi / Q000378:metabolism / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D004848:Epithelium / Q000378:metabolism; D066246:ErbB Receptors / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053552:Keratin-7 / Q000096:biosynthesis*; D019394:Ki-67 Antigen / Q000096:biosynthesis*; D011230:Precancerous Conditions / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
chemical_list: D066246:ErbB Receptors; D053552:Keratin-7; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53; C512478:EGFR protein, human