Jan. 9, 2006 Scientists at Johns Hopkins have found that a mutation in the gene that triggers production of a tumor growth protein is linked to poorer outcomes for patients with papillary thyroid cancer (PTC). A report on the study is published in the December issue of The Journal of Clinical Endocrinology and Metabolism.
Mingzhao Xing, M.D., Ph.D., an assistant professor in the Division of Endocrinology and Metabolism at The Johns Hopkins University School of Medicine, led the multi-center study. “This discovery should help physicians rate risk levels for patients with PTC,” he says.
The gene, called BRAF, is part of a signaling pathway that, when activated, is known to cause tumor growth, and mutations in BRAF have been linked to a variety of human cancers, the researchers say.
For the study, Xing and colleagues looked at information from 219 PTC patients from 1990 to 2004. The relationship among BRAF mutations, initial tumor characteristics, cancer recurrence and clinical outcomes was analyzed.
Results showed a “significant association” between BRAF mutation and spread of the cancer from the thyroid, lymph node metastasis, and advanced tumor stage at the time of surgery to remove the cancerous thyroid gland. The thyroid, a gland located beneath the voice box (larynx) that produces thyroid hormone, helps regulate body cell growth and metabolism. Results also showed that, given an average follow-up of three to four years, 25 percent of patients with BRAF mutations experienced tumor recurrence compared to 9 percent without evidence of BRAF mutations.
BRAF mutation was also an independent predictor of recurrence in patients with early disease, with 22 percent recurrence in those who had BRAF mutations versus only 5 percent in patients without the mutation.
Finally, BRAF mutation was more frequently associated with treatment failure in recurrent disease, according to the study.
“By illustrating a higher risk of poorer outcomes and recurrence, these results should help physicians perform better risk analysis of patients with PTC, which in turn will lead to more tailored treatment of the disease,” Xing said.
PTC is the most common thyroid cancer, accounting for 80 percent or more of thyroid malignancies. Although PTC is usually curable with surgical removal of the gland, often followed by radioiodine treatment, many cases recur and are fatal.
The ability to predict outcome has traditionally been based on such factors as patient age and gender, tumor size and the nature of the spread of disease. However, these criteria often leave uncertainty regarding the risk of tumor progression and recurrence.
“What we have is a novel molecular diagnostic tool that will improve existing clinical efforts,” Xing said.
The study patients were recruited from The Johns Hopkins University School of Medicine; The Yale University School of Medicine; The Hospital for Endocrine Surgery in Kiev, Ukraine; and The University of Bologna Hospital in Bologna, Italy.
Other contributors from Hopkins include William H. Westra, M.D., professor in the Department of Pathology; Ralph P. Tufano, M.D, assistant professor in the Department of Otolaryngology -- Head and Neck Surgery; David Sidransky, M.D., professor in the Department of Otolaryngology -- Head and Neck Surgery, and Paul W. Ladenson, M.D., director of the Division of Endocrinology and Metabolism.
The study was supported by grants from the National Institutes of Health and the Flight Attendant Medical Research Institute.
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