3p21, 5q21, and 9p21 allelic deletions are frequently found in normal bronchial cells adjacent to non-small-cell lung cancer, while they are unusual in patients with no evidence of malignancy

Molecular cytogenetic and loss of heterozygosity (LOH) analyses of non-smal l-cell lung cancer (NSCLC) have shown frequent allelic deletions in a varie ty of chromosomes, such as 1p, 3p, 5q, 8p, 9p, 11p, 11q, and 17p. Allelic l oss at 3p21, 9p21, and 5q21 has also been reported in premalignant epitheli al lesions of the bronchus and in normal bronchial cells. These findings su ggest that a tissue field of somatic genetic alterations precedes the histo pathological phenotypic changes of carcinoma. LOH at chromosomal regions 3p 21, 5q21, 9p21, and 17p (TP53) was looked for in the peritumoural normal br onchial cells from 30 archival surgically resected tumours. Microdissected normal bronchial cells from 20 benign cytological smears were also added to the study. Matched populations of lymphocytes, tumour cells, and normal br onchial cells adjacent to the tumour were microdissected from, paraffin-emb edded tissues, while matched populations of normal bronchial cells and infl ammatory cells were microdissected from benign cytological smears (bronchia l brushings). Polymerase chain reaction (PCR) amplification was performed u tilizing the specific markers D5S346, D3S1300, D9S157, D9S171, and TP53. Wi thin the NSCLC tumour cells, LOH was more frequently found at the 5q21: loc us (72% of the informative cases), the 3p21 locus (47%), 9p21 (48%.), and 1 7p (33%.). Within the peritumoural normal bronchial cells, LOH at 5q21 was found in 37.5%, of the cases, 22%, showed LOH at 3p21, 27%, at 9p21, and U- Mi, at 17p (TP53). LOH was also detected in one case, in normal bronchial c ells obtained from cytological smears at one locus (5q21). In conclusion, n ormal bronchial mucosa adjacent to NSCLC has frequent allelic losses at 3p2 1, 5q2l, and 9p21, while LOH at these loci is unusual in normal bronchial c ells obtained from cytological smears from patients with no evidence of mal ignancy. LOH at these loci may be present before the onset of the malignant growth. LOH studies may supplement the histopathological evaluation of bro nchial cells to detect genotypic alterations in both cytological and biopsy specimens. Copyright (C) 2001 John Wiley & Sons, Ltd.