Abstract
The detection of micrometastasis holds great promise for earlier staging of patients with malignant diseases and may ultimately guide therapeutic decisions. So far, reverse-transcriptase polymerase chain reaction (RT-PCR) amplification of genes expressed by the tumor in a tissue-specific manner is the method with the highest diagnostic sensitivity. It is well-established that the identification of single tumor cells is feasible in tissues and bodily fluids in both experimental and clinical samples. However, at present it is difficult to assign clinical significance to results obtained from such tests, primarily because their diagnostic specificity is disputed, both conceptionally and methodologically. For example, amplification of candidate mRNA targets is detectable in non-cancer patients using conditions that generally fail to generate such signals from healthy individuals. We have established that transcription of the tissue-specific genes can be affected by different means. Specifically, some target mRNA species are detectable in peripheral blood nuclear cells as low abundance constitutive-like expression, whereas others are induced through in vitro tissue culturing. In addition, mRNA expression may be distinctly upregulated by different cytokines or growth factors in vivo. Also, background transcription of target mRNAs can occur in different lineages of peripheral blood cells. Finally, expression may be substantially different in tissues such as peripheral blood, bone marrow, or lymph nodes. As a consequence, cancer patients in unrelated clinical situations may present with different levels of background expression, making the diagnostic specificity of test results difficult to assess. To add to this complexity, an increasing body of literature is being generated using various targets for a multitude of malignant diseases. There is a great variety of methods for sampling, specimen processing, nucleic acids recovery, test conditions, and readout formats, making it impossible to compare data. In summary, modalities of quantitative RT-PCR methods and standardization issues should be discussed to address these questions.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Battayani Z, Grob JJ, Xerri L, Noe C, Zarour H, Houvaeneghel G, Delpero JR, Birmbaum D, Hassoun J, Bonerandi JJ (1995) Polymerase chain reaction detection of circulating melanocytes as a prognostic marker in patients with melanoma. Arch Dermatol 131: 443–447
Bergh J, Norberg T, Sjögren S, Lindgren A, Holmberg L (1995) Complete sequencing of the p53 gene provides prognostic information in breast cancer patients, particularly in relation to adjuvant systemic therapy and radiotherapy. Nature Medicine 1: 1029–1034
Brossart P, Schmier JW, Kruger S, Willhauck M, Scheibenbogen C, Mohler T, Keilholz U (1995) A polymerase chain reaction-based semiquantitative assessment of malignant melanoma cells in peripheral blood. Cancer Res 55: 4065–4068
Burchill SA, Bradbury FM, Smith B, Lewis IJ, Selby P (1994) Neuroblastoma cell detection by reverse transcriptase-polymerase chain reaction ( RT-PCR) for tyrosine hydroxylase mRNA. Int J Cancer 57: 671–675
Cama C, Olsson CA, Raffo AJ, Perlman H, Buttyan R, O’Toole K, McMahon D, Benson MC, Katz AE (1995) Molecular staging of prostate cancer. II: A comparison of the application of an enhanced reverse transcriptase polymerase chain reaction assay for the prostate specific antigen versus the prostate specific membrane antigen. J Urol 153: 1373–1378
Coller HA, Khrapko K, Torres A, Frampton MW, Utell MJ, Thilly WG (1998) Mutational spectra of a 100-base pair mitochondria) DNA target sequence in bronchial epithelial cells: a comparison of smoking and nonsmoking twins. Cancer Res 58: 1268–1277
Cote RJ, Rosen PP, Lesser ML, Old LJ, Osborne MP (1991) Prediction of early relapse in patients with operable breast cancer by detection of occult bone marrow micrometastases. J Clin Oncol 9: 1749–1756
Dearnaley DP, Ormerod MG, Sloane JP, Lumley H, Imrie S, Jones M, Coombes RC, Neville AM (1983) Detection of isolated mammary carcinoma cells in marrow of patients with primary breast cancer. J R Soc Med 76: 359–364
Dearnaley DP, Sloane JP, Ormerod MG, Steele K, Coombes RC, Clink HM, Powles TJ, Ford HT, Gazet JC, Neville AM (1981) Increased detection of mammary carcinoma cells in marrow smears using antisera to epithelial membrane antigen. Br J Cancer 44: 85–90
Diel IJ, Kaufmann M, Görner R, Costa SD, Kaul S, Bastert G (1992) Detection of tumor cells in bone marrow of patients with primary breast cancer: A prognostic factor for distant metastasis. J Clin Oncol 10: 1–5
Eaton MC, Hardingham JE, Kotasek D, Dobrovic A (1997) Immunobead RT-PCR: a sensitive method for detection of circulating tumor cells. Biotechniques 22: 100–105
Gerhard M, Juhl H, Kalthoff H, Schreiber HW, Wagener C, Neumaier M (1994) Specific detection of carcinoembryonic antigen ( CEA)-expressing tumor cells in bone marrow aspirates by PCR. J Clin Oncol 12: 725–729
Ghossein RA, Osman I, Bhattacharya S, Ferrara J, Fazzari M, Cordon-Cardo C, Scher HI (1999) Detection of prostatic specific membrane antigen messenger RNA using immunobead reverse transcriptase polymerase chain reaction. Diagn Mol Pathol 8: 59–65
Gomella LG, Raj GV, Moreno JG (1997) Reverse transcriptase polymerase chain reaction for prostate specific antigen in the management of prostate cancer [see comments]. J Urol 158: 326–337
Gusterson B (1991) Are micrometastases clinically relevant? Br J Hospital Med 47:247–248.
Hardingham JE, Kotasek D, Sage RE, Eaton MC, Pascoe VH, Dobrovic A (1995) Detection of circulating tumor cells in colorectal cancer by immunobead-PCR is a sensitive prognostic marker for relapse of disease. Mol Med 1:789–794
Jung R, Ahmad-Nejad P, Wimmer M, Gerhard M, Wagener C, Neumaier M (1997) Quality management and influential factors for the detection of single metastatic cancer cells by reverse transcriptase polymerase chain reaction. Eur J Clin Chem Clin Biochem 35: 3–10
Jung R, Kruger W, Hosch S, Holweg M, Kroger N, Gutensohn K, Wagener C, Neumaier M, Zander AR (1998) Specificity of reverse transcriptase polymerase chain reaction assays designed for the detection of circulating cancer cells is influenced by cytokines in vivo and in vitro. Br J Cancer 78: 1194–1198
Khrapko K, Coller HA, Hanekamp JS, Thilly WG (1998) Identification of point mutations in mixtures by capillary electrophoresis hybridization. Nucleic Acids Res 26: 5738–5740
Lehrer S, Terk M, Piccoli SP, Song HK, Lavagnini P, Luderer AA (1996) Reverse transcriptase-polymerase chain reaction for prostate-specific antigen may be a prognostic indicator in breast cancer. Br J Cancer 74: 871–873
Liefers GJ, Cleton-Jansen AM, van de Velde CJ, Hermans J, van Krieken JH, Cornelisse CJ, Tollenaar RA (1998) Micrometastases and survival in stage II colorectal cancer. N Engl J Med 339: 223–228
Lindblom A (1998) Improved tumor staging in colorectal cancer [editorial; comment]. N Engl J Med 339: 264–265
Lindemann F, Schlimok G, Dirschedl P, Witte J, Riethmüller G (1992) Prognostic significance of micrometastatic tumour cells in bone marrow of colorectal cancer patients. Lancet 340: 685–689
Matsumura M, Niwa Y, Kato N, Komatsu Y, Shiina S, Kawabe T, Kawase T, Toyoshima H, Ihori M, Shiratori Y, et al (1994) Detection of alpha-fetoprotein mRNA, an indicator of hematogenous spreading hepatocellular carcinoma, in the circulation: a possible predictor of metastatic hepatocellular carcinoma. Hepatology 20: 1418–1425
Mattano LA, Jr, Moss TJ, Emerson SG (1992) Sensitive detection of rare circulating neuroblastoma cells by the reverse transcriptase-polymerase chain reaction. Cancer Res 52: 4701–4705
Neumaier M, Gerhard M, Wagener C (1995) Diagnosis of micrometastases by the amplification of tissue-specific genes. Gene 159: 43–47
Pantel K, Izbicki JR, Angstwurm M, Braun S, Passlick B, Karg O, Thetter O, Riethmüller G (1993) Immunocytological detection of bone marrow micrometastasis in operable non-small lung cancer. Cancer Res 53: 1027–1031
Pantel K, Riethmüller G (1995) Methods for detection of micrometastatic carcinoma cells in bone marrow, blood and lymph nodes. Onkologie 18: 394–401
Riethmüller G, Schneider Gadicke E, Schlimok G, Schmiegel W, Raab R, Hoffken K, Gruber R, Pichlmaier H, Hirche H, Pichlmayr R et al (1994) Randomised trial of monoclonal antibody for adjuvant therapy of resected Dukes’ C colorectal carcinoma. German Cancer Aid 17–1A Study Group. Lancet 343: 1177–1183
Yu H, Giai M, Diamandis EP, Katsaros D, Sutherland DJ, Levesque MA, Roagna R, Ponzone R, Sismondi P (1995) Prostate-specific antigen is a new favorable prognostic indicator for women with breast cancer. Cancer Res 55: 2104–2110
Zippelius A, Kufer P, Honold G, Kollermann MW, Oberneder R, Schlimok G, Riethmüller G, Pantel K (1997) Limitations of reverse-transcriptase polymerase chain reaction analyses for detection of micrometastatic epithelial cancer cells in bone marrow. J Clin Oncol 15: 2701–2708
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2001 Springer-Verlag Berlin · Heidelberg
About this paper
Cite this paper
Jung, R., Soondrum, K., Krüger, W., Neumaier, M. (2001). Detection of Micrometastasis Through Tissue-Specific Gene Expression: Its Promise and Problems. In: Reinhold, U., Tilgen, W. (eds) Minimal Residual Disease in Melanoma. Recent Results in Cancer Research, vol 158. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-59537-0_4
Download citation
DOI: https://doi.org/10.1007/978-3-642-59537-0_4
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-64015-5
Online ISBN: 978-3-642-59537-0
eBook Packages: Springer Book Archive