Molecular detection of thyroglobulin mRNA transcripts in peripheral blood of patients with thyroid disease by RT-PCR.
The sensitive detection of circulating tumour cells in patients with differentiated thyroid cancer may precede the detection of relapse by other diagnostic studies--such as serum thyroglobulin-and thus may have important therapeutic and prognostic implications. We performed reverse transcription-polymerase chain reaction (RT-PCR) on blood samples from patients diagnosed with thyroid disease using two different RT-PCR sensitivities. Additionally, tissue specificity of TG mRNA-expression was determined using RNA extracts from 27 different human tissues. The lower limit of detection was 50-100 TG mRNA producing cells/ml blood using a 'normal' RT-PCR sensitivity and 10-20 cells/ml blood using a 'high' sensitivity. With the normal sensitivity TG mRNA was detected in 9/13 patients with thyroid cancer and metastasis, 63/137 patients with a history of thyroid cancer and no metastasis, 21/85 with non-malignant thyroid disease and 9/50 controls. With the high sensitivity TG mRNA was detected in 11/13 patients with thyroid cancer and metastasis, 111/137 patients with a history of thyroid cancer and no metastasis, 61/85 with non-malignant thyroid disease and 41/50 controls. Interestingly, using the normal RT-PCR sensitivity TG mRNA transcripts are specific for thyroid tissue and detectable in the peripheral blood of controls and patients with thyroid disease, which correlates with a diagnosis of metastasized thyroid cancer. However, with a high RT-PCR sensitivity, TG mRNA expression was found not to be specific for thyroid tissue and was not correlated with a diagnosis of thyroid cancer in patients. As a consequence, to date TG mRNA detected by RT-PCR in the peripheral blood cannot be recommended as a tumour marker superior to TG serum-level.
Bojunga
J
J
Department of Medicine I, JW Goethe-University, Frankfurt am Main, Germany.
Röddiger
S
S
Stanisch
M
M
Kusterer
K
K
Kurek
R
R
Renneberg
H
H
Adams
S
S
Lindhorst
E
E
Usadel
K H
KH
Schumm-Draeger
P M
PM
D016022:Case-Control Studies; D006042:Goiter / Q000097:blood; D006111:Graves Disease / Q000097:blood; D006801:Humans; D009928:Organ Specificity; D012333:RNA, Messenger / Q000097:blood*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods*; D012680:Sensitivity and Specificity; D013954:Thyroglobulin / Q000097:blood*; D013959:Thyroid Diseases / Q000097:blood*; D013964:Thyroid Neoplasms / Q000097:blood; D013967:Thyroiditis, Autoimmune / Q000097:blood
D012333:RNA, Messenger; D013954:Thyroglobulin