Chromosomal aneuploidy precedes morphological changes and supports multifocality in head and neck lesions

Objective. To identify chromosome changes associated with the transformatio n of dysplastic lesions and to verify evidence for multifocality in synchro nous premalignant lesions associated with head and neck squamous cell carci noma (HNSCC). Study Design: Chromosomal aneuploidy was evaluated in section s of formalin-fixed, paraffin-embedded tissues from 16 patients with HNSCC, including sites with normal squamous mucosa, dysplasia (low- and high-grad e), and invasive tumor. Methods: A panel of 6 centromeric probes (chromosom es 1, 3, 7, 8, 9, and 17) was analyzed in dual-color fluorescence in situ h ybridization assays, using matched hematoxylin-eosin-stained sections for h istologic correlation. Results: Imbalances for most of the targets tested w ere found in 20 of 24 invasive carcinoma sites, mainly represented by gain in copy number per cell. However, cell populations with chromosome losses a nd gains in multimodal patterns were concomitantly observed in a number of tumors, indicating a high degree of chromosome instability. The detection o f chromosomal aneuploidy precedes the malignant transformation as indicated by findings of monosomy and trisomy in normal squamous mucosa, and in low- grade and high-grade dysplasia sites. Loss of chromosomes 3 and 17 prevaile d in low-grade dysplasias, and gain of chromosomes 7 and 8 were prevalent i n high-grade dysplasias. Synchronous low-grade and high-grade dysplastic le sions displayed discordant molecular signatures, suggesting a multifocal. o rigin. Conclusions: The interphase fluorescence in-situ hybridization (FISH ) assay with centromeric may detect early changes in the progression of dyp lastic epithelia to invasive carcinoma and supports the field cancerization theory of multifocality.