Genotype-phenotype correlations in hereditary medullary thyroid carcinoma:Oncological features and biochemical properties

In hereditary medullary thyroid carcinoma (MTC), few genotype-phenotype cor relations have been established. RET genotypes (exons 10, 11, 13, and 14) o f 63 patients with hereditary MTC (from November 1994 to October 1999) were correlated with age at diagnosis, sex, the TNM system, and basal calcitoni n levels. Mutations in exons 10, 11, 13, and 14 were demonstrated in 22% (1 4 of 63), 54% (34 of 63), 21% (13 of 63), and 3% (2 of 63). The median ages at diagnosis differed significantly (38, 27, 52, and 62 yr; P = 0.003). Wh en grouped by cysteine codons (exons 10 and 11 us. exons 13 and 14), this d ifference became even more evident (30 us. 56 yr; P = 0.001). Apart from ag e at diagnosis, no other significant associations were noted. Based hereon, three MTC risk groups were devised according to genotype: a high risk grou p (codons 634 and 618) with the youngest ages of3 and 7 yr at diagnosis; an intermediate risk group (codons 790, 620, and 611) with ages of 12, 34, an d 42 yr; and a low risk group (codons 768 and 804) with ages of 47 and 60 y r, respectively. Age at diagnosis was unrelated to specific nucleotide and amino acid exchange within each codon. The current data demonstrate that there is a significant genotype-phenotype correlation, allowing for a more individualized approach to the timing and extent of prophylactic surgery.