Thyroid Cancer: Increase in BRAF, RAS Mutations

Yuri E. Nikiforov, M.D., Ph.D. Professor of Pathology Vice Chair for Molecular Pathology Director, Division of Molecular & Genomic Pathology Department of Pathology University of Pittsburgh Pittsburgh, PA 15213MedicalResearch.com Interview
Yuri E. Nikiforov, M.D., Ph.D.
Professor of Pathology, Vice Chair for Molecular Pathology
Director, Division of Molecular & Genomic Pathology
Department of Pathology, University of Pittsburgh Pittsburgh, PA

MedicalResearch.com: What are the main findings of the study?

Dr. Nikiforov: This is examined temporal changes in mutational profiles and standardized histopathologic features of thyroid cancer in the U.S. over the last four decades. It showed a significant change in molecular profiles of thyroid cancer during the past 40 years as it determined two major trends in changing the mutational make-up of thyroid cancer: a rapid increase in the prevalence of RAS mutations, particularly for the last 10 years, and continuous decrease in frequency of RET/PTC rearrangement. The rising incidence of RAS mutations points to new and more recent etiologic factors, probably of a chemical or dietary nature. The decreasing incidence of RET/PTC rearrangements, a known marker of high-dose environmental and medical radiation, suggest that the impact of ionizing radiation, at least as related to high-dose environmental exposures and historical patterns of radiation treatment for benign conditions, is diminishing.

MedicalResearch.com: Were any of the findings unexpected?

Dr. Nikiforov: One of the unexpected finding was a stable and high incidence of BRAF mutations. These mutations are known to occur in progressive and clinically relevant cancers, and this finding suggests that the continuous increase in the incidence of thyroid cancer observed in the U.S. and many other countries is unlikely to be only due to better surveillance leading to the detection of small, non-progressing, and clinically irrelevant cancers.

MedicalResearch.com: What should clinicians and patients take away from your report?

Dr. Nikiforov: That the increasing incidence of thyroid cancer is likely to be real and is not simply due to overdiagnosing thyroid cancer. The study we report does not imply that all or most thyroid cancers are aggressive and have to be treated extensively, but it suggests that this disease requires attention and that early diagnosis and appropriate treatment is important.

MedicalResearch.com:  What recommendations do you have for future research as a result of this study?

Dr. Nikiforov: The study shows, for the first time in any cancer type, a significant change in molecular profiles of thyroid cancer during the past 40 years. The obtained data suggest that the molecular landscape of thyroid cancer, and likely of other cancer types, is not static and changes over time, probably reflecting the constant change in environmental factors and behavioral patterns of humans. It means that the data on mutational profiles being obtained for multiple cancer types, reflect the situation at the time of the study and may not be extrapolated longitudinally. Additional studies are needed to answer the question if the molecular profiles of all major cancer types evolve over time.

Citation:

The increase in thyroid cancer incidence during the last four decades is accompanied by a high frequency of BRAF mutations and a sharp increase in RAS mutations

J Clin Endocrinol Metab. 2013 Nov 18. [Epub ahead of print]

Jung CK, Little MP, Lubin JH, Brenner AV, Wells SA Jr, Sigurdson AJ, Nikiforov YE.

Department of Pathology (C.K.J., Y.E.N.), University of Pittsburgh, Pittsburgh, PA, 15261, USA; Department of Hospital Pathology (C.K.J.), The Catholic University of Korea, Seoul 137-701, Republic of Korea; Radiation Epidemiology and Biostatistics Branches (J.H.L., A.V.B., M.P.L. A.J.S.), Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA; Cancer Genetics Branch, National Cancer Institute, (S.A.W.) National Institutes of Health, Bethesda, MD, 20892, USA