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[Cancer Research 57, 1690-1694, May 1, 1997]
© 1997 American Association for Cancer Research
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Distinct Pattern of ret Oncogene Rearrangements in Morphological Variants of Radiation-induced and Sporadic Thyroid Papillary Carcinomas in Children1

Yuri E. Nikiforov, Jon M. Rowland, Kevin E. Bove, Hector Monforte-Munoz and James A. Fagin2

Division of Endocrinology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0547 [Y. E. N., J. A. F.]; Department of Pathology, Childrens Hospital Los Angeles, Los Angeles, California 90027 [J. M. R., H. M-M.]; and Department of Pathology, Childrens Hospital Medical Center, Cincinnati, Ohio 45229 [K. E. B.]

In this study, we compare the morphological and genetic characteristics of 38 post-Chernobyl thyroid papillary carcinomas from Belarussian children 5–18 years old with those of 23 sporadic papillary carcinomas from the same age children without history of radiation exposure from Los Angeles and Cincinnati. Among radiation-induced tumors, solid variant of papillary carcinoma was found in 37%, follicular in 29%, typical papillary in 18%, and mixed and diffuse sclerosing variants in 8% each. In the sporadic group, a typical papillary pattern was prevalent in 70%, follicular in 17%, diffuse sclerosing variant in 9%, and solid in 4%. In both groups, the prevalence of ret rearrangements was high, but the frequency of specific types of rearrangement was significantly different. Among radiation-induced tumors, ret/PTC3 was found in 58%, ret/PTC1 in 16%, and ret/PTC2 in 3%, whereas among sporadic tumors, ret/PTC1 was found in 47% (P < 0.05), and ret/PTC3 was found in 18% (P = 0.01). The morphological variants of papillary carcinoma showed different prevalence of the specific types of ret rearrangement. Seventy-nine % of solid variant tumors had ret/PTC3, whereas only 7% had ret/PTC1 (P = 0.0007). Among typical papillary tumors, ret/PTC1 was found in 38%, ret/PTC3 in 19%, and ret/PTC2 in 5%. Thus, ret rearrangements are highly prevalent in pediatric papillary carcinomas from children exposed to radiation and in those occurring sporadically. However, the types of ret/PTC vary between these two populations, with ret/PTC3 present more commonly in post-Chernobyl tumors. Furthermore, solid variants have a high prevalence of ret/PTC3, whereas typical papillary carcinomas do not, suggesting that the different types of ret rearrangement confer neoplastic thyroid cells with distinct phenotypic properties.

1 This work was supported in part by Grants CA 50706 and CA 72597 and a University of Cincinnati Cancer Research Challenge Award. J. A. F. is the recipient of an Established Investigatorship Award from the American Heart Association and Bristol Myers-Squibb.

2 To whom requests for reprints should be addressed, at Division of Endocrinology/Metabolism, University of Cincinnati College of Medicine, P. O. Box 670547, Cincinnati, OH 45267-0547. Phone: (513) 558-4444; Fax (513) 558-8581.

Received 11/ 4/96. Accepted 3/10/97.




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J. Biol. Chem., August 13, 1999; 274(33): 23414 - 23425.
[Abstract] [Full Text] [PDF]

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 Am. J. Pathol.Home page
F. Cetta, M. R. Pelizzo, M. C. Curia, and A. Barbarisi
Genetics and Clinicopathological Findings in Thyroid Carcinomas Associated with Familial Adenomatous Polyposis
Am. J. Pathol., July 1, 1999; 155(1): 7 - 9.
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 J. Clin. Endocrinol. Metab.Home page
F. Cetta, M. Gori, N. Raffaelli, C. Baldi, G. Montalto, D. L Learoyd, and B. G Robinson
RET/PTC and RET Tyrosine Kinase Expression in Adult Papillary Thyroid Carcinomas--Authors' Response
J. Clin. Endocrinol. Metab., June 1, 1999; 84(6): 2258 - 2258.
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 J. Clin. Endocrinol. Metab.Home page
F. Cetta, M. Gori, N. Raffaelli, C. Baldi, and G. Montalto
Comment on Clinical and Prognostic Relevance of Ret-PTC Activation in Patients with Papillary Thyroid Carcinoma
J. Clin. Endocrinol. Metab., June 1, 1999; 84(6): 2257a - 2258.
[Full Text]