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.

Heterogeneity in Lung Cancer

“…We have studied EGFR expression in these pre-neoplastic lesions, demonstrating its increasing expression in lesions in this spectrum; therefore, EGFR and its respective pathways may play a role in early steps of epidermoid carcinoma development, reflecting the importance of EGFR signalling transduction pathways in pre-neoplastic lesions [1]. Other studies also corroborate these results [2][3][4][5][6][7][8][9].…”

“…An increasing expression of these markers was observed [1]. The study reinforced the utility of Ki-67 as a biomarker for dysplasia, a group of pre-neoplastic lesions characterized by a higher proliferative index, also identified by other authors [1,[12][13][14][15][16][17].…”

“…The sequence basal cell hyperplasia -squamous metaplasiasquamous dysplasia -squamous carcinoma is well defined. Our research group also demonstrated molecular changes in this spectrum of lesions, reflecting the severity and biological aggressiveness along the spectrum of lesions, using immunohistochemical markers such as Ki-67, p53, EGFR, and HER2 and also evaluating EGFR and HER2 gene copy number [1].…”

“…EGFR, Ki-67, and p53 might play a role in the identification of epidermoid carcinoma pre-neoplastic lesions at higher risk of developing epidermoid carcinoma [1].…”

Severe dysplasia can be distinguished from moderate and mild dysplasia of bronchial mucosa by changes in Ki-67 index

“…Also, Cavarga et al [27] and Hoshino et al [28] indicated that increases in Ki-67 expression in preneoplastic lesions might be associated with the development of bronchogenic carcinomas and possibly with acquisition of an invasive phenotype. Ki-67 appears to correlate with the progression of the malignant processes from the preneoplastic to the invasive stage [29], and may be useful in predicting prognosis in patients with non small-cell lung cancer [30]. However, further studies are needed to explore this concept.…”