Bromodeoxyuridine incorporation in differentiated thyroid cancer

Objective: Bromodeoxyuridine (BUdR), a thymidine analog, is incorporated into the DNA in the synthetic (S) phase of the cell cycle. BUdR uptake quantifies DNA synthesis and helps predict the prognosis of various cancers. We, therefore, studied BUdR uptake in differentiated thyroid cancers to determine whether it correlates with other clinical prognostic factors in patients with differentiated thyroid cancer. Materials and Methods: Fresh thyroid cancer tissue from 45 patients was incubated in 10 μm BUdR in Dulbecco's modified Eagle medium with 10% fetal calf serum for 1 hour at 37°C, fixed in 70% ethanol and embedded in paraffin. Five μm sections were deparaffinized, denatured, and incubated for 1 hour in 1:3000 purified monoclonal antibodies. The immunohistochemical staining was performed using the avidin-biotin peroxidase complex technique. The extent of BUdR incorporation was measured using the labeling index (% of total cells labeled with BUdR). Results: BUdR labeling index was lower in good risk cancers confined to the thyroid (DeGroot Class I) or regional nodes (DeGroot Class II) (0.65%±0.23%, N=26) than in poor risk cancers with local invasion (DeGroot Class III) or distant metastases (DeGroot Class IV) (1.13%±0.67%, N=19) (P=0.002 using the t-test). BUdR labeling index was similarly lower in cancers from low risk patients with AGES score < 4 (0.66%±0.27%, N=29) than those from high risk patients with AGES score ≥ 4 (1.19%±0.69%, N=16) (P=0.001 using the t-test). BUdR labeling index correlated with patient age (r=0.313, p=0.001), and tumor size (r=0.479, p=0.001). Six patients had tumor BUdR labeling indexes greater than 1.5%. All had DeGroot Class III or IV cancers and had AGES scores greater than 4. Conclusions: We concluded that BUdR labeling index correlated with tumor size, patient age, and risk classification of DeGroot Class or AGES score in patients with differentiated thyroid cancer, and it may become a useful factor in predicting thyroid cancer behavior.