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Proliferative Activity of Human Thyroid Cells in Various Age Groups and Its Correlation with the Risk of Thyroid Cancer after Radiation Exposure

Department of Pathology and Laboratory Medicine (A.G.S., S.K., J.S., Y.E.N.), University of Cincinnati, Cincinnati, Ohio 45267; Division of Cancer Epidemiology and Genetics (E.R., J.H.L.), National Cancer Institute, Bethesda, Maryland 20892; and Division of Pathology and Laboratory Medicine (K.E.B.), Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio 45229

Address all correspondence and requests for reprints to: Dr. Yuri Nikiforov, Department of Pathology, University of Cincinnati, 231 Albert Sabin Way, P.O. Box 670529, Cincinnati, Ohio 45267-0529. E-mail: Yuri.Nikiforov{at}uc.edu.

Context: The thyroid gland is vulnerable to the carcinogenic effects of ionizing radiation, and there is a well-documented inverse correlation between thyroid cancer and age at exposure, particularly for ages less than 20 yr. One of the factors responsible for this phenomenon may be more rapid cell proliferation in children.

Objective: The objective of this study was to determine the proliferative rate of normal human thyroid cells in different age groups.

Design: We used immunohistochemical analysis to determine the Ki-67 proliferative index in 117 thyroid glands obtained at autopsy, including 25 fetal thyroids (11–40 wk gestation), 55 childhood thyroids (0–19 yr), and 37 adult thyroids (20–60 yr).

Results: The rate of Ki-67 labeling in the three groups was 7.4 ± 6.10, 0.23 ± 0.15, and 0.08 ± 0.04% respectively, demonstrating an overall trend for diminishing proliferative activity of thyroid cells with increasing age. However, a lack of correlation was noted between the slopes of cancer risk calculated from previous studies of irradiated populations and proliferative rate in the pediatric age intervals of 0–4 and 5–9 yr, suggesting that other factors are likely to be responsible for the particularly high sensitivity to radiation-induced thyroid cancer among the youngest children.

Conclusions: Our findings of a general decrease in proliferative activity of thyroid cells with age may explain, at least in part, the higher risks of radiation-related thyroid cancer in children compared with adults. However, the variation in the rate of cell proliferation is unlikely to be responsible entirely for this phenomenon and other factors may also be involved.

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