We measured the tumor cell proliferative rate in 26 patients with head
and neck cancer, 22 of which were squamous cell carcinomas (SCCs). Pa
tients received sequential infusions of iododeoxyuridine and bromodeox
yuridine, after which the tumor was biopsied and studied, The percenta
ge of labeled cells [labeling index (LI)] in well-differentiated SCCs
was 20.4 +/- 2.7% (mean +/- SE) and 23.8 +/- 2.1% in moderately differ
entiated SCCs (P = 0.135). The LIs of two poorly differentiated SCCs w
ere 39.4 and 55.9%. The LI was 2.5% in a high-grade lymphoepithelioma
and 24.8% in a malignant lymphoma, In one well-differentiated and one
poorly differentiated mucoepidermoid tumor, the LIs were 3.0% and 29.1
%, respectively, S-phase duration time measurements ranged from 5.1-21
.5 h (12.8 +/- 1.5). The calculated potential doubling times ranged fr
om 18.8-84.5 h (47.3 +/- 6.7), The duration of G(2) was between 90 and
180 min. To track the fate of labeled cells, in four patients a repea
t biopsy was obtained 7-14 days after the iododeoxyuridine/bromodeoxyu
ridine infusion. These patients did not receive treatment between the
biopsies, Due to the dilution of the label, most labeled cells in the
second biopsy demonstrated a ''fragmented'' pattern resulting from rep
eated cell divisions, In two patients, however, 25% of cells in the se
cond biopsy had undiluted label, suggesting that these cells had not d
ivided after incorporating iododeoxyuridine/bromodeoxyuridine, On Day
7 labeled cells migrated to keratinized parts of tumors and to necroti
c foci. Thus, the arrest of cell cycle transition, tumor cell differen
tiation, and cell death may be major routes of tumor cell loss from th
e proliferative compartment. This may explain the difference between v
ery short potential doubling times and the actual rate of tumor growth
.