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RET Mutation in Medullary Thyroid Cancer Predicts Worse Survival
October 18, 2007 — Patients with medullary thyroid carcinoma (MTC) who have a somatic RET mutation have a worse outcome and a significantly lower survival rate than those without this mutation. While this relationship has been suggested before, the association is now confirmed in a study of 100 patients with a 10-year follow-up reported by Cristina Romei, MD, from the University of Pisa, Italy, at the American Thyroid Association 78th Annual Meeting, in New York.
Dr. Romei and colleagues studied 100 patients with medullary thyroid carcinoma (43 males, 57 females) who had a mean age of 49.6 years at diagnosis. The RET gene exons 10,11, 13 14, 15, and 16 were analyzed by direct sequencing.
Genetic analysis revealed a somatic RET mutation in 43 of 100 sporadic MTCs, which fits in with rates of between 40% to 50% that have been reported in previous studies, Dr. Romei commented. The most frequent mutation (in 34 of 43 patients, 79%) was the Met918→Thr in exon 16, she reported. The team also found 7 mutations at codon 634, 1 mutation at codon 883, and a 48 base-pair deletion in exon 10.
RET mutations were more frequent in patients who had bigger tumors (P = .02) and in patients who had lymph node metastases (P < .0001). Also, RET mutations were found to be correlated with the persistence of the disease (both biochemical and metastatic). Comparing the 20-year survival curves of patients who had somatic RET mutations with those who did not revealed a significantly lower percentage of patients with RET mutations surviving (P = .006), Dr. Romei reported.
\"In conclusion, we demonstrated that somatic RET mutation correlates with the presence of lymph node metastases at diagnosis, with a worse outcome in terms of persistence of disease and a significantly lower survival rate,\" Dr. Romei told the meeting.
Asked by Medscape Oncology to comment on this finding, Jayne Franklyn, MD, PhD, from Queen Elizabeth Hospital, in Birmingham, United Kingdom, who was not involved with the study, said: \"This is an important study, as it involved a large number of patients with a relatively rare form of thyroid cancer, specifically looking at those with the sporadic or noninherited variety of this cancer, and it presents the intriguing possibility that the presence of the mutation is associated with a prediction of tumor behavior and therefore prognosis.\" There could be potential clinical implications, but first these findings need to be replicated in other studies in other parts of the world, she continued. This study also \"adds to the broader picture emerging that defining gene mutations and gene expressions in various sorts of thyroid cancer provides prognostic information,\" Dr. Franklyn commented.
American Thyroid Association 78th Annual Meeting: Abstract 91. Presented October 4, 2007
美国甲状腺协会第78届年会：摘要91 ，2007年10月4日呈现 |
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发表于 2007-10-23 07:24:44