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Ionizing radiation is the strongest risk factor known for the development of thyroid neoplasia. While previous studies have demonstrated a high prevalence of ret/papillary thyroid cancer (PTC) activation in cohorts of patients developing thyroid nodules after childhood exposure to ionizing radiation, no study has directly compared ret/PTC activation with individual estimates of radiation dose to the thyroid. This study combines individual thyroid dosimetry data with molecular analysis of surgically removed thyroid nodules in order to determine if ret/PTC activation in thyroid nodules is associated with increasing estimated radiation dose from Chernobyl.This pilot study included adults and children diagnosed with PTC (n = 76) and children diagnosed with follicular adenomas (n = 24) during May 1986 through December 1999, who were living in the Bryansk Oblast of the Russian Federation at the time of the Chernobyl accident, who had paraffin-embedded thyroid surgical samples available and for whom an individual dose to the thyroid could be estimated. The frequency of ret/PTC activation was determined using RT-PCR analysis. Individual radiation doses to the thyroid were estimated using a semiempirical model, and data were collected by detailed interview, primarily of the participant's mother.ret/PTC oncogene activation was detected in 23.8% (5/21) and 14.5% (8/55) of the childhood and adult PTC cases, respectively, and 8.3% (2/24) of the follicular adenoma cases. No statistically significant differences were noted in age at the time of exposure or diagnosis, gender, latency period, or estimated radiation dose between PTC patients with or without ret/PTC activation. Further, no significant dose-response relationship was detected among PTC patients with ret/PTC activation.Factors other than individual thyroid radiation doses may influence the development and subsequent detection of ret/PTC oncogene activation in radiation related PTC arising in the Bryansk Oblast of the Russian Federation in the aftermath of the Chernobyl accident.

Erythropoietin (EPO) and the EPO receptor (EPO-R) have been implicated in solid tumors of the brain, breast, kidney and female genital tract. Based on their expression by a variety of tumors, we hypothesized that EPO and/or EPO-R might be expressed by thyroid cancers. To test this, we determined EPO and EPO-R expression by immunohistochemistry in 17 papillary thyroid carcinomas (PTC) from children and adolescents. Only a minority of PTC (4/17, 24%) expressed EPO, and there were no significant differences between the PTC that did or did not express EPO. In contrast, EPO-R was detected in the majority of PTC (11/17, 65%). The average tumor size (1.5 +/- 0.8 cm), MACIS score (3.6 +/- 0.2) and risk of recurrence (0/11) for the EPO-R(+) PTC were significantly less than those for PTC that failed to express EPO-R (average tumor size = 3.6 +/- 2.4 cm, p = 0.021; average MACIS score = 4.3 +/- 0.7, p = 0.004; recurrence = 3/6, p = 0.029). We conclude that the majority of PTC from children and adolescents express EPO-R, a finding associated with favorable prognostic indicators and a lower risk of recurrence.