Specific steps in aneuploidization correlate with loss of heterozygosity of 9p21, 17p13 and 18q21 in the progression of pre-malignant laryngeal lesions

Laryngeal squamous-cell carcinoma is often preceded by pre-malignant lesion s. In this study, pre-malignant as well as malignant laryngeal lesions were analyzed using p53 immunohistochemistry and in situ hybridization for chro mosomes 1, 7, 9, 17 and 18. Microsatellite analysis was performed on laser- microdissected tissue fragments with the aim of studying loss of heterozygo sity (LOH) of 9p21, 17p13 and 18q21. Sequential biopsies were analyzed from a few cases to study genetic progression in more detail. The following gen etic progression patterns were observed: (i) histologically normal mucosa a nd hyperplastic lesions without malignant progression were typically disomi c for all chromosomes tested and showed no or only basal cell layer positiv ity for p53 and no allelic loss; (ii) hyperplastic lesions preceding dyspla stic/invasive growth frequently showed trisomy for chromosome 7 and LOH of 9p21 and 17p13, and small foci within these lesions sometimes showed tetrap loidization and p53 positivity; (iii) dysplastic lesions were characterized by a tetraploid chromosome content, LOH of 9p21 and 17p13 and p53 positivi ty; (iv) carcinoma in situ lesions and invasive laryngeal carcinomas showed a more unbalanced chromosome pattern and an additional 18q21 LOH, These re sults show that different steps in aneuploidization correlate with LOH of 9 p21, 17p13 and 18q21 in early laryngeal carcinogenesis. These genomic chang es could be of potential use in the diagnosis and prognosis of pre-malignan t laryngeal lesions, (C) 2001 Wiley-Liss, Inc.