ret/PTC1 and ret/PTC3 in thyroid tumors from Chernobyl liquidators: comparison with sporadic tumors from Ukrainian and French patients

Abstract

Like children exposed to Chernobyl fallout, the workers who cleaned up after the accident, also known as liquidators, have exhibited an increased incidence of thyroid cancer. A high prevalence of ret /PTC3 rearrangement has been found in pediatric post-Chernobyl thyroid tumors, but this feature has not been investigated in liquidator thyroid tumors. In this study we analyzed the prevalence of ret /PTC1 and ret /PTC3 in thyroid tumors from 21 liquidators, 31 nonirradiated adult Ukrainian patients, and 34 nonirradiated adult French patients. ret rearrangements in carcinomas were found in 83.3% of liquidators, 64.7% of Ukrainian patients, and 42.9% of French patients. The prevalence of ret /PTC1 was statistically similar in the three groups. The prevalence of ret /PTC3 was significantly higher in liquidators than in French patients (P=0.03) but it was also high in nonirradiated Ukrainian patients who exhibited values intermediate between liquidators and French patients. In adenomas the prevalence of rearrangement was significantly higher in all Ukrainians than in French patients (P=0.004). Like children exposed to Chernobyl fallout, liquidators showed a high prevalence of ret /PTC3. This finding suggests that irradiation had the same effect regardless of age. However, given the high rate of ret /PTC3 in nonirradiated adult Ukrainians, the possibility of genetic susceptibility or low-level exposure to radiation in that group cannot be excluded.

Expression of tpo mRNA in thyroid tumors: quantitiative PCR analysis and correlation with alterations of ret, Braf , ras and pax8 genes

“…patient age over 35 years in most cases, higher frequency of advanced tumor stage and purely papillary histology. These three features have been correlated with Braf mutations and ret/PTC previously (Cohen et al 2003, Kim et al 2004, Nikiforova et al 2004, Trovisco et al 2004, Di Cristofaro et al 2005, Xing et al 2004. The antagonism between oncogene activation of the ERK signaling cascade and expression of differentiated functions by thyroid cells has been confirmed by expression array analysis and may explain the inhibition of tpo expression in PC (Melillo et al 2005).…”

Molecular genetic study comparing follicular variant versus classic papillary thyroid carcinomas: association of N-ras mutation in codon 61 with follicular variant

“…More than 10 ret/PTCs have been described, but ret/PTC1 and ret/PTC3 are the most frequent and account for more than 90% of cases. The prevalence of these rearrangements varies from 5% to more than 80%, depending on clinical and environmental factors [16][17][18][19]. Evidence correlating ret/PTC1 with CPTC and occult PTC and ret/PTC3 with solid and tall-cell variants have been reported, but the correlation between ret/PTC rearrangements and follicular differentiation of PTC has received less attention and current evidence is contradictory [19][20][21][22].…”

Diagnostic Limitation of Fine-Needle Aspiration (FNA) on Indeterminate Thyroid Nodules Can Be Partially Overcome by Preoperative Molecular Analysis: Assessment of RET/PTC1 Rearrangement in BRAF and RAS Wild-Type Routine Air-Dried FNA Specimens

“…RET/PTC rearrangements are commonly found in adult sporadic PTCs with a marked variable prevalence in different studies owing to geographic variability or different sensitivity of the detection methods [17,29,30,31,32,33,34,35,36,37]. The reported prevalence rates of RET/PTC rearrangements varied largely among studies.…”

“…Rates of 0–54.5% have been reported in Asia [30,31,32], 2.4–72.0% in the United States [17,33], and 8.1–42.9% in Europe [34,35]. The marked variations may reflect the small size of the studies, geographic variability, or different sensitivities of the detection methods [36,37].…”