PROLIFERATION OR EPITHELIA OF NONINVOLVED MUCOSA IN PATIENTS WITH HEAD AND NECK-CANCER

Background. Morphologically noninvolved mucosa in patients with head a nd neck cancer is altered by carcinogens. These alterations may includ e chromosome alterations, gene mutations, and other molecular abnormal ities which may explain very high incidence of second tumors in this g roup of patients. The purpose of this study was to investigate the in vivo proliferative characteristics in epithelial tissues adjacent to t he tumor in a series of patients with head and neck cancer. Methods. T wenty-one patients with head and neck tumors received IV infusions of iododeoxyuridine (IdUrd) and/or bromodeoxyuridine (BrdUrd). Surgical s pecimens 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 b asal and suprabasal layers of the epithelium. Results. In 27 samples o f oral epithelium obtained from 14 previously untreated patients, labe led (S-phase) cells were predominantly located in suprabasal layers wi th LI 31.6 +/- 3.1% (range 13.5-73.2%). in contrast, the LI of the bas al layer was very low: 1.6 +/- 0.2% (range 0.5%-8.8%). There was no st atistically significant difference between normal appearing and dyspla stic samples (p > 0.05). In 10 samples obtained from 7 patients whose biopsies were studied 2 days to 2 month after concomitant radiation an d chemotherapy, the LI of the oral mucosa basal layer was significantl y higher (21.0 +/- 4.1%, range 6.3-39.2%). The LI of the suprabasal la yer 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 tl of ''basal'' cells was 8.3% (range 5.9-11.9%) and that of ''supraba sal'' 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 s uprabasal layers of skin was 21.3% (range 7.8-33.2%). Conclusion. Both the frequency and the spatial distribution of S-phase cells are disor dered in noninvolved epithelia in patients with head and neck tumors. These observations suggest that disordered proliferation may be an ear ly consequence of field cancerization, a consequence that occurs prior to appearance of morphologically apparent hyperplasia or dysplasia. ( C) 1996 John Wiley & Sons, Inc.