Background: Morphologically noninvolved mucosa in patients with head and neck cancer is altered by carcinogens. These alterations may include chromosome alterations, gene mutations, and other molecular abnormalities which may explain very high incidence of second tumors in this group of patients. The purpose of this study was to investigate the in vivo proliferative characteristics in epithelial tissues adjacent to the tumor in a series of patients with head and neck cancer.
Methods: Twenty-one patients with head and neck tumors received IV infusions of iododeoxyuridine (IdUrd) and/or bromodeoxyuridine (BrdUrd). Surgical specimens containing normal-appearing epithelium adjacent to the tumor were selected and stained with the respective monoclonal antibody. The percentage of S-phase cells (labeling index, LI) was counted in the basal and suprabasal layers of the epithelium.
Results: In 27 samples of oral epithelium obtained from 14 previously untreated patients, labeled (S-phase) cells were predominantly located in suprabasal layers with LI 31.6 +/- 3.1% (range 13.5-73.2%). In contrast, the LI of the basal layer was very low: 1.6 +/- 0.2% (range 0.5%-8.8%). There was no statistically significant difference between normal appearing and dysplastic samples (p > 0.05). In 10 samples obtained from 7 patients whose biopsies were studied 2 days to 2 month after concomitant radiation and chemotherapy, the LI of the oral mucosa basal layer was significantly higher (21.0 +/- 4.1%, range 6.3-39.2%). The LI of the suprabasal layer in treated patients was 14.3 +/- 2.4% (range 5.9-31.1%). The LI of nasal pseudostratified epithelium (4 samples) was 11.2%. The average LI of "basal" cells was 8.3% (range 5.9-11.9%) and that of "suprabasal" cells was 13.8% range (3.2-29.5%). The basal layer of the skin (5 samples) contained 9.3% labeled cells (range 3.3-16.3%); the LI of suprabasal layers of skin was 21.3% (range 7.8-33.2%).
Conclusion: Both the frequency and the spatial distribution of S-phase cells are disordered in noninvolved epithelia in patients with head and neck tumors. These observations suggest that disordered proliferation may be an early consequence of field cancerization, a consequence that occurs prior to appearance of morphologically apparent hyperplasia or dysplasia.