External
carcinogens, such as tobacco and alcohol, induce molecular changes in large areas of oral mucosa, which increase the risk of malignant transformation. This condition, known as 'field cancerization', can be detected in biopsy specimens using histochemical techniques, even before histological alterations are identified. The efficacy of these histochemical techniques as
biomarkers of early cancerization must be demonstrated in appropriate models. The hamster cheek pouch
oral cancer model, universally employed in
biological studies and in studies for the prevention and treatment of
oral cancer, is also an excellent model of field cancerization. The
carcinogen is applied in
solution to the surface of the mucosa and induces alterations that recapitulate the stages of cancerization in human oral mucosa. We have demonstrated that the following can be used for the early detection of cancerized tissue:
silver staining of nucleolar organizer regions; the Feulgen reaction to
stain DNA followed by ploidy analysis; immunohistochemical analysis of
fibroblast growth factor-2, immunohistochemical labeling of proliferating cells to demonstrate an increase of epithelial cell proliferation in the absence of
inflammation; and changes in markers of angiogenesis (i.e. those indicating
vascular endothelial growth factor activity, endothelial cell proliferation and vascular density). The hamster cheek pouch model of
oral cancer was also proposed and validated by our group for
boron neutron capture therapy studies for the treatment of
oral cancer. Clinical trials of this novel treatment modality have been performed and are underway for certain
tumor types and localizations. Having demonstrated the efficacy of
boron neutron capture therapy to control
tumors in the hamster cheek pouch
oral cancer model, we adapted the model for the long-term study of field cancerized tissue. We demonstrated the inhibitory effect of
boron neutron capture therapy on
tumor development in field cancerized tissue with acceptable levels of
mucositis, a dose-limiting side-effect.