Document Detail


Quantitative reverse transcription-polymerase chain reaction of circulating thyroglobulin messenger ribonucleic acid for monitoring patients with thyroid carcinoma.
MedLine Citation:
PMID:  10566646     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Patients with thyroid cancer are monitored for disease recurrence by measurement of serum thyroglobulin (Tg) and iodine-131 (131I) scanning. To enhance sensitivity and to circumvent antibodies that interfere with Tg immunoassays, we have developed RT-PCR assays that detect circulating thyroid messenger RNA (mRNA) transcripts. We now report results using a sensitive quantitative Tg mRNA assay (Taqman; ABI, Foster City, CA) in comparison with immunoassay in patients previously treated for thyroid cancer. We evaluated 107 patients: 84 during T4 therapy, 14 after T4 withdrawal, and 9 at both time points. All patients had near-total thyroidectomy, and 92% received postoperative 131I. Serum TSH, Tg protein, and Tg mRNA were measured. Patients were grouped based on most recent 131I scan or pathologically confirmed disease as having no detectable thyroid tissue (n = 33), thyroid bed uptake (n = 37), cervical/regional adenopathy (n = 21), or distant metastases (n = 16). During T4 therapy, median (range) Tg mRNA values (pg Tg Eq/microg thyroid RNA) for the groups were 1.5 (0-26.8), 9.4 (0.5-90.0), 15.4 (0.2-92), and 12.4 (1.9-16.6), respectively. Using a value of 3 pg Tg Eq/microg thyroid RNA as cut-point, Tg mRNA was positive in 38% of patients with no uptake, 75% with thyroid bed uptake, 84% with cervical/regional disease, and 94% with distant metastases. The median Tg mRNA value for patients with no uptake was lower than the median values for patients with thyroid bed uptake (P = 0.009) or with detectable thyroid tissue at any site (P = 0.010). Patients with negative 131I whole body scans were also less likely to have detectable Tg mRNA levels than were patients with thyroid bed uptake (P < 0.001) or any detectable thyroid tissue at any location (P < 0.001). Similar differences between these groups were seen after T4 withdrawal and for the 23 patients with circulating anti-Tg antibodies, when analyzed separately. Eight of the nine patients studied with low and high TSH concentrations displayed greater amounts of circulating Tg mRNA after T4 withdrawal. In three patients followed prospectively, the amount Tg mRNA correlated with the presence and absence of cervical metastases. In conclusion, we have demonstrated that a quantitative Tg mRNA assay can identify thyroid cancer patients with recurrent or residual thyroid tissue with greater sensitivity and similar specificity to Tg immunoassay during T4 therapy. The assay was unaffected by anti-Tg antibodies, responded to TSH-stimulation, and was reduced after surgical removal of metastases. These data suggest that this quantitative Tg mRNA assay may be a sensitive marker of tumor recurrence or response to therapy, particularly in patients with anti-Tg antibodies.
Authors:
M D Ringel; P L Balducci-Silano; J S Anderson; C A Spencer; J Silverman; Y H Sparling; G L Francis; K D Burman; L Wartofsky; P W Ladenson; M A Levine; R M Tuttle
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  84     ISSN:  0021-972X     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  1999 Nov 
Date Detail:
Created Date:  1999-11-26     Completed Date:  1999-11-26     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  4037-42     Citation Subset:  AIM; IM    
Affiliation:
Department of Medicine, Washington Hospital Center and Medstar Research Institute, Washington, DC 20010, USA. mxr9@mhg.edu
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MeSH Terms
Descriptor/Qualifier:
Adenocarcinoma, Follicular / blood,  radionuclide imaging,  therapy
Autoantibodies / blood
Carcinoma, Papillary / blood,  radionuclide imaging,  therapy
Female
Humans
Immunoassay
Iodine Radioisotopes / diagnostic use
Male
Neoplasm Recurrence, Local / blood,  diagnosis*,  radionuclide imaging
Prospective Studies
RNA, Messenger / blood*
Reverse Transcriptase Polymerase Chain Reaction*
Sensitivity and Specificity
Thyroglobulin / blood,  genetics*,  immunology
Thyroid Neoplasms / blood*,  radionuclide imaging,  therapy
Thyroidectomy
Thyrotropin / blood
Thyroxine / administration & dosage,  therapeutic use
Chemical
Reg. No./Substance:
0/Autoantibodies; 0/Iodine Radioisotopes; 0/RNA, Messenger; 7488-70-2/Thyroxine; 9002-71-5/Thyrotropin; 9010-34-8/Thyroglobulin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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