The two-mutational-event theory in medullary thyroid cancer.

Comparisons are presented of the ages of onset of 20 cases of hereditary medullary carcinoma of the thyroid (MCT) and of 22 sporadic cases of this same type of cancer. These data are compatible with what might be expected by the two-mutational-event theory of the initiation of cancer postulated by Knudson. It had been previously postulated that C-cell hyperplasia of the thyroid was a premalignant change resulting from the first or genetic mutational event in the initiation of this type of cancer. The finding of C-cell hyperplasia in thyroid glands of each of the 10 patients with the hereditary condition and in none of the 10 sporadic patients is compatible with this theory. The C-cell hyperplasia is believed to be the expression of the genetic mutation, which requires a subsequent somatic mutation to transform the initially mutated cell into a cancer cell.