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. 2000 Apr 27;82(10):1650–1655. doi: 10.1054/bjoc.1999.1209

Molecular detection of thyroglobulin mRNA transcripts in peripheral blood of patients with thyroid disease by RT-PCR

J Bojunga 1, S Röddiger 1, M Stanisch 1, K Kusterer 1, R Kurek 2, H Renneberg 3, S Adams 4, E Lindhorst 5, K H Usadel 1, P M Schumm-Draeger 1
PMCID: PMC2374521  PMID: 10817499

Abstract

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. © 2000 Cancer Research Campaign

Keywords: polymerase chain reaction, reverse transcription, thyroid cancer, thyroglobulin mRNA, molecular diagnostics

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Selected References

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  1. Altschul S. F., Gish W., Miller W., Myers E. W., Lipman D. J. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. doi: 10.1016/S0022-2836(05)80360-2. [DOI] [PubMed] [Google Scholar]
  2. Aust G., Crisp M., Bösenberg E., Ludgate M., Weetman A. P., Paschke R. Transcription of thyroid autoantigens in non-expressing tissues. Exp Clin Endocrinol Diabetes. 1998;106(4):319–323. doi: 10.1055/s-0029-1211992. [DOI] [PubMed] [Google Scholar]
  3. Bellantone R., Lombardi C. P., Boscherini M., Ferrante A., Raffaelli M., Rubino F., Bossola M., Crucitti F. Prognostic factors in differentiated thyroid carcinoma: a multivariate analysis of 234 consecutive patients. J Surg Oncol. 1998 Aug;68(4):237–241. doi: 10.1002/(sici)1096-9098(199808)68:4<237::aid-jso6>3.0.co;2-5. [DOI] [PubMed] [Google Scholar]
  4. Chelly J., Concordet J. P., Kaplan J. C., Kahn A. Illegitimate transcription: transcription of any gene in any cell type. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2617–2621. doi: 10.1073/pnas.86.8.2617. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Datta Y. H., Adams P. T., Drobyski W. R., Ethier S. P., Terry V. H., Roth M. S. Sensitive detection of occult breast cancer by the reverse-transcriptase polymerase chain reaction. J Clin Oncol. 1994 Mar;12(3):475–482. doi: 10.1200/JCO.1994.12.3.475. [DOI] [PubMed] [Google Scholar]
  6. Ditkoff B. A., Marvin M. R., Yemul S., Shi Y. J., Chabot J., Feind C., Lo Gerfo P. L. Detection of circulating thyroid cells in peripheral blood. Surgery. 1996 Dec;120(6):959–965. doi: 10.1016/s0039-6060(96)80041-9. [DOI] [PubMed] [Google Scholar]
  7. Gerfo P. L., Colacchio T., Colacchio D., Feind C. Thyroglobulin in benign and malignant thyroid disease. JAMA. 1979 Mar 2;241(9):923–924. [PubMed] [Google Scholar]
  8. Ghossein R. A., Rosai J. Polymerase chain reaction in the detection of micrometastases and circulating tumor cells. Cancer. 1996 Jul 1;78(1):10–16. doi: 10.1002/(SICI)1097-0142(19960701)78:1<10::AID-CNCR3>3.0.CO;2-L. [DOI] [PubMed] [Google Scholar]
  9. Ghossein R. A., Scher H. I., Gerald W. L., Kelly W. K., Curley T., Amsterdam A., Zhang Z. F., Rosai J. Detection of circulating tumor cells in patients with localized and metastatic prostatic carcinoma: clinical implications. J Clin Oncol. 1995 May;13(5):1195–1200. doi: 10.1200/JCO.1995.13.5.1195. [DOI] [PubMed] [Google Scholar]
  10. Haber R. S. The diagnosis of recurrent thyroid cancer--a new approach. J Clin Endocrinol Metab. 1998 Dec;83(12):4189–4190. doi: 10.1210/jcem.83.12.5376. [DOI] [PubMed] [Google Scholar]
  11. Herle A. J., Uller R. P. Elevated serum thyroglobulin. A marker of metastases in differentiated thyroid carcinomas. J Clin Invest. 1975 Aug;56(2):272–277. doi: 10.1172/JCI108090. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hoang-Vu C., Dralle H., Scheumann G., Maenhaut C., Horn R., von zur Mühlen A., Brabant G. Gene expression of differentiation- and dedifferentiation markers in normal and malignant human thyroid tissues. Exp Clin Endocrinol. 1992;100(1-2):51–56. doi: 10.1055/s-0029-1211176. [DOI] [PubMed] [Google Scholar]
  13. Johnson P. W., Burchill S. A., Selby P. J. The molecular detection of circulating tumour cells. Br J Cancer. 1995 Aug;72(2):268–276. doi: 10.1038/bjc.1995.324. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Loh K. C., Greenspan F. S., Gee L., Miller T. R., Yeo P. P. Pathological tumor-node-metastasis (pTNM) staging for papillary and follicular thyroid carcinomas: a retrospective analysis of 700 patients. J Clin Endocrinol Metab. 1997 Nov;82(11):3553–3562. doi: 10.1210/jcem.82.11.4373. [DOI] [PubMed] [Google Scholar]
  15. Malthiéry Y., Lissitzky S. Primary structure of human thyroglobulin deduced from the sequence of its 8448-base complementary DNA. Eur J Biochem. 1987 Jun 15;165(3):491–498. doi: 10.1111/j.1432-1033.1987.tb11466.x. [DOI] [PubMed] [Google Scholar]
  16. Mattano L. A., Jr, Moss T. J., Emerson S. G. Sensitive detection of rare circulating neuroblastoma cells by the reverse transcriptase-polymerase chain reaction. Cancer Res. 1992 Sep 1;52(17):4701–4705. [PubMed] [Google Scholar]
  17. Moreno J. G., Croce C. M., Fischer R., Monne M., Vihko P., Mulholland S. G., Gomella L. G. Detection of hematogenous micrometastasis in patients with prostate cancer. Cancer Res. 1992 Nov 1;52(21):6110–6112. [PubMed] [Google Scholar]
  18. Noguchi M., Katev N., Miwa K. Therapeutic strategies and long-term results in differentiated thyroid cancer. J Surg Oncol. 1998 Jan;67(1):52–59. doi: 10.1002/(sici)1096-9098(199801)67:1<52::aid-jso12>3.0.co;2-x. [DOI] [PubMed] [Google Scholar]
  19. Parker S. L., Tong T., Bolden S., Wingo P. A. Cancer statistics, 1997. CA Cancer J Clin. 1997 Jan-Feb;47(1):5–27. doi: 10.3322/canjclin.47.1.5. [DOI] [PubMed] [Google Scholar]
  20. Ringel M. D., Ladenson P. W., Levine M. A. Molecular diagnosis of residual and recurrent thyroid cancer by amplification of thyroglobulin messenger ribonucleic acid in peripheral blood. J Clin Endocrinol Metab. 1998 Dec;83(12):4435–4442. doi: 10.1210/jcem.83.12.5346. [DOI] [PubMed] [Google Scholar]
  21. Sanders L. E., Cady B. Differentiated thyroid cancer: reexamination of risk groups and outcome of treatment. Arch Surg. 1998 Apr;133(4):419–425. doi: 10.1001/archsurg.133.4.419. [DOI] [PubMed] [Google Scholar]
  22. Schlumberger M. J. Papillary and follicular thyroid carcinoma. N Engl J Med. 1998 Jan 29;338(5):297–306. doi: 10.1056/NEJM199801293380506. [DOI] [PubMed] [Google Scholar]
  23. Schlumberger M., Tubiana M., De Vathaire F., Hill C., Gardet P., Travagli J. P., Fragu P., Lumbroso J., Caillou B., Parmentier C. Long-term results of treatment of 283 patients with lung and bone metastases from differentiated thyroid carcinoma. J Clin Endocrinol Metab. 1986 Oct;63(4):960–967. doi: 10.1210/jcem-63-4-960. [DOI] [PubMed] [Google Scholar]
  24. Simpson W. J., McKinney S. E., Carruthers J. S., Gospodarowicz M. K., Sutcliffe S. B., Panzarella T. Papillary and follicular thyroid cancer. Prognostic factors in 1,578 patients. Am J Med. 1987 Sep;83(3):479–488. doi: 10.1016/0002-9343(87)90758-3. [DOI] [PubMed] [Google Scholar]
  25. Tallini G., Ghossein R. A., Emanuel J., Gill J., Kinder B., Dimich A. B., Costa J., Robbins R., Burrow G. N., Rosai J. Detection of thyroglobulin, thyroid peroxidase, and RET/PTC1 mRNA transcripts in the peripheral blood of patients with thyroid disease. J Clin Oncol. 1998 Mar;16(3):1158–1166. doi: 10.1200/JCO.1998.16.3.1158. [DOI] [PubMed] [Google Scholar]

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