Does loss of heterozygosity in critical genome regions predict a local relapse in patients after laryngectomy?

摘要

BACKGROUND: Patients, who had an upper aerodigestive tract malignancy, have a high incidence of succeeding tumor development. This has been attributed to the role of "field cancerization" in carcinogenesis. The aim of this study was analysis of loss of heterozygosity (LOH) in the regions frequently lost during the course of head and neck squamous cell carcinomas (HNSCC), especially at early stages, which could answer the clinicians' question, if LOH analysis has any "predictive" value in relation to tumor occurrence. MATERIAL AND METHODS: Sixty-five larynx cancer patients were examined for loss of heterozygosity on 3p, 7q, 8p, 9p and 18q chromosomal arms with the use of 12 microsatellite markers. The material from a single patient consisted of blood, tumor, safe margin and one or two clinically unchanged mucosal samples. During follow up, the material from brush specimens (14 patients) as well as laryngeal swabs (4 patients) was also examined. RESULTS: The highest frequency of LOH was detected for marker D3S1234 in tumor tissues (29%). Analysis of margin samples (b) revealed low LOH frequencies (2-5%) and complete retention of heterozygosity for markers: D3S1234, D7S486, D8S261, D8S264, D9S171 and D18S46. Similarly, for normal appearing mucosa from upper part of larynx (c) frequencies of LOH were low (2-6%), with the complete retention of heterozygosity for markers: D3S1284, D3S1304, D3S1234, D8S264 and D9S1870. We did not detect any LOH in the material of normal appearing mucosa from tracheostoma region (d). During follow up, LOH was detected for eight markers, with the highest incidence for markers D18S46 (six cases), D7S486 (four cases) and D3S1300 (three cases). CONCLUSIONS: The data, obtained during this investigation, did not reveal the predictive value of LOH with respect to local relapse occurrence in laryngeal cancer patients. However, time of follow up did not reach 5 years, so that further clinical monitoring should be conducted.