Abstract
Although expression of the bcl-2 protein has been investigated in a number of non-haematological malignancies, little is known of its distribution in premalignant lesions. Expression of bcl-2 was investigated immunohistochemically in archival biopsies of normal (n = 8) and dysplastic bronchial epithelium (n = 56) and in 31 bronchial resection margins and their corresponding carcinomas. All dysplasias had lost the prominent basal staining pattern seen in histologically normal epithelium. Two were negative and six had occasional basal positive cells. In 37 cases up to 66% of the epithelial cells throughout the full epithelial thickness were bcl-2 positive with weak to moderate staining intensity. In 11 cases, all severe dysplasias, strong expression was observed in > 90% of the epithelial cells. Four patterns of bcl-2 expression in dysplasias were identified and an increasingly aberrant pattern of bcl-2 expression correlated with an increasing grade of dysplasia (Spearman's rank correlation, P < or = 0.0001). Sixty-five per cent of the carcinomas contained bcl-2-positive cells. Patients with non-small-cell lung carcinomas (n = 27) in which > 50% of the tumour cells were bcl-2 positive showed a survival advantage compared with those with 0-25% bcl-2-positive cells (P = 0.02). No correlation was found between p53 expression (Walker et al., 1994) and bcl-2 expression in dysplasias or carcinomas.
Highlights
Lung tssuesC Wakr et a 165 analysis was by the log-rank test. Two-tailed probabilities are quoted for all statistical tests
In 37 ca up to 66% of the epitheial cells throughout the full epithelial thickness were positive with weak to moderate staining intensity
Lung carcinomas arise after a series of morphological and genetic changes within the bronchial epithelium, and it may take years to progress from normal epithelium to invasive cancer
Summary
C Wakr et a 165 analysis was by the log-rank test. Two-tailed probabilities are quoted for all statistical tests. Fifty-six formalin-fixed, paraffin-embedded bronchial biopsies which had been reported to contain dysplastic epithelium were retrieved from the archives at the Histopathology Department, Broadgreen HospitaL Liverpool, UK. Eight formalin-fixed, paraffin-embedded bronchial biopsies and four resction margins, taken from patients who did not have lung cancer at the time of removal and which contained epithelium reported as histologically normal, were obtained from the files. Thirty-one formalin-fixed, paraffin-embedded specimens of lung carcinoma and their corresponding bronchial resection margins were colleted prospectively by Dr N Pendleton from lobectomies or pneumonectomies performed at the Cardiothoracic Centre, Liverpool, UK. Sections were reviewed for bcl-2 positivity and the intensity of stained cells scored as negative, weak, moderate or strong. In normal and dysplastic epithelium, the proportions of bcl-2-positive epithelial cells and their distribution according to the thickness of the epithelium containing these cells was recorded. Immunoreactivity to p53 in cases that had not previously been investigated was determined as described in Walker et al (1994) using the CMI antibody (Novaastra)
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