Detection of thyroglobulin, thyroid peroxidase, and RET/PTC1 mRNA transcripts in the peripheral blood of patients with thyroid disease.

PURPOSE: Detection of mRNA transcripts for thyroglobulin (TG), thyroid peroxidase (TPO) and RET/PTC1 in the peripheral blood of patients with thyroid disease. PATIENTS AND METHODS: TG, TPO, and RET/PTC1 mRNA were analyzed in 52 peripheral-blood samples from 44 patients diagnosed with thyroid carcinoma (24 patients), adenoma (five patients), and nodular hyperplasia (15 patients) by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: TG and TPO were identified in 13 patients (54.2%) with thyroid carcinoma, which includes five of eight patients with no clinical evidence of disease at the time of blood collection. Four of 5 patients had cervical lymph node metastases and/or extrathyroid extension at the time of the initial surgery. RET/PTC1 mRNA was detected in the peripheral blood of only one patient with papillary thyroid carcinoma. This sample was also positive for TG and TPO. TG and TPO were detected in two patients (10%) with benign thyroid nodules. All positive samples from patients with benign thyroid lesions were collected before surgery, whereas all samples collected after surgery were negative. RET/PTC1 mRNA was not detected in any of the patients with benign thyroid nodules. RT-PCR positivity for TG and TPO mRNA was higher in patients with carcinoma than in patients with benign lesions (P = .002). CONCLUSION: TG, TPO, and RET/PTC1 mRNA are detectable in the peripheral blood of patients with thyroid disease, which correlates with a diagnosis of carcinoma.

Clinical presentations and RET protooncogene mutations in seven multiple endocrine neoplasia type 2 kindreds.

BACKGROUND: Multiple endocrine neoplasia type 2 (MEN 2) is a group of related autosomal dominant cancer syndromes caused by mutations in the RET protooncogene. A subset of familial Hirschsprung's disease, aganglionic megacolon, is also caused by mutations in this gene. METHODS: The authors performed mutation analysis of exons 10, 11, 13, and 16 of the RET gene is six established MTN 2 kindreds and in six patients with apparent sporadic disease, in order to correlate their genotypes and phenotypes. RESULTS: One of these kindred's carried both Hirschsprung's disease and MEN 2A in conjunction with a cysteine-to-arginine substitution of codon 620 of the RET gene. One patient with apparently sporadic disease was found to have a germline M918T mutation. Patients with confirmed familial disease all carried pathologic germline mutations of RET. CONCLUSIONS: Several lines of evidence support a gain of function mechanism for tumorigenesis in the MEN 2 syndromes but a loss of function mechanism for aganglionosis in Hirschsprung's disease. The authors propose that a multihit mechanism can reconcile the apparent paradox of a single mutation that gives rise to both gain and loss of function disorders in a single patient.