Head and neck cancer development has been proposed to represent a multistage process characterized by dysregulation of proliferation and differentiation and driven by an accumulation of genetic alterations in an anatomic field repeatedly exposed to carcinogens. To visualize the accumulation of genetic alterations during head and neck tumorigeneses and to determine the extent of the genetically altered field, we probed 25 squamous cell carcinomas of the head and neck and their adjacent premalignant lesions for numerical chromosome aberrations by nonisotopic, in situ hybridization using chromosome-specific centromeric DNA probes for chromosomes 7 and 17. Normal control oral epithelium from individuals free of cancer showed no chromosome polysomy (i.e., cells with ≥3 chromosome copies), whereas histologically normal epithelium adjacent to the tumors showed squamous cells with polysomies for chromosomes 7 and 17. Moreover, the frequency of cells with polysomy increased as the tissues passed from histologically normal epithelium to hyperplasia to dysplasia to cancer. The finding of genotypic abnormalities in histologically normal and precancerous regions adjacent to the tumor supports the concept of field cancerization. The finding of progressive genetic changes as the tumor develops supports the concept of multistep carcinogenesis in the head and neck region. Such genotypic parameters could serve as biomarkers in the assessment of the risk of progression to malignancy and as intermediate end points in chemoprevention trials.
Supported in part by NIH Grants CA52501, CA48364, and CA45746 and the Ripple Foundation. This work also utilized the facilities of the Flow Cytometry Core Facility supported by NIH-National Cancer Institute Core Grant CA16672 to Dr. Frederick Becker, N. V. was the recipient of a University Cancer Foundation Clinical Fellowship, D. M. S. is a recipient of the Clinical Oncology Career Development Award (ACS 91-271) from the American Cancer Society.