Evidence for the 'field cancerization' theory is not seen by comparative genomic hybridization analysis of squamous cell carcinoma of the larynx

Abstract

Patients with cancers of the upper aerodigestive tract have a high incidence of developing synchronous or metachronous primary tumours. Currently it is unclear whether these primary tumours are of monoclonal or polyclonal origin. The hypothesis of ‘field cancerization’ where the local region has been transformed after exposure to a common carcinogenic compound, has been proposed to account for the development of multiple primary tumours. We have investigated whether common changes in gene copy number can be detected in histologically normal samples associated with squamous cell carcinomas of the larynx. The technique of comparative genomic hybridization (CGH) was utilized. Biopsy samples were taken from the tumour site, the 1-cm margin, and a distant 5 cm site from 10 patients undergoing resection of a laryngeal carcinoma. Genomic DNA was extracted from these biopsies, nick-labelled with fluorescein dUTP and was competitively hybridized with Texas Red-labelled normal DNA. CGH slides were analysed on a QUIPS Genetics Work-station (Vysis). None of the 1-cm or 5-cm biopsy samples showed any changes in DNA copy number. A pathologist reviewed the slides, which showed only one area of severe dysplasia (<10% of sample). Distinct patterns of aberrations were seen in the tumour biopsies. Common deletions: 3p (80%), 5q (50%), 11q (50%), 13q (50%) and 4q (30%); common amplifications: 3q (70%), 11q (50%), 8q (50%), 5p (30%), 1q (30%). The formation of the 3q isochromosome was seen in 60% of tumours. This study shows no evidence of a generalized transformation of the mucosa when measuring gene copy number. However, CGH analysis has shown a number of common chromosomal aberrations in laryngeal tumours.