Abstract
Introduction
Recent studies have identified both the prognostic and predictive utility of determining the number of circulating tumour cells (CTC) in patients with solid cancers.
Material and methods
In the present pilot study we evaluated the ability of two different methods to isolate CTC in combination with two strategies to enumerate CTC from patients with stages II and III surgically treated colorectal cancer (CRC). First, we used two systems for tumour cell enrichment (differential centrifugation and immunomagnetic beads), combined with two methods to enumerate CTC (real-time PCR and flow cytometry), to determine the most efficient combination. These experiments were performed in a model system using serial dilutions of HT29 tumour cell lines with lymphocytes. Then, CTC analysis using the technical approach selected before was performed in 109 blood samples from 16 stage II and III CRC patients during chemotherapy treatment and follow-up.
Results
Immunomagnetic beads followed by flow cytometry was the most efficient combination (ED=60.53; p=0.5). Two cases out of 16 patients analysed had clinical tumour relapse. In both, we detected a significant increase of CTC five and six months, respectively, before the relapse was clinically evidenced. An increase of CTC was also observed in another case without clinical evidence of relapse. The remaining cases (13) had very few or no detectable CTC and no clinical evidence of relapse (p=0.029).
Conclusions
Changes in CTC numbers during follow-up might predict tumour relapse. Further evaluation of CTC prognostic and predictive value in patients with early CRC is warranted.
Similar content being viewed by others
References
http://www.seom.org/es/prensa/el-cancer-enespanyacom?showall=1
Andre T, Boni C, Navarro M et al (2009) Improved survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol 27:3109–3116
Wolpin BM, Meyerhardt JA, Mamon HJ et al (2007) Adjuvant treatment of colorectal cancer. CA Cancer J Clin 57:168–185
Johnstone EC, Kerr DJ (2008) What is the role and impact of molecular markers on treatment decisions in the adjuvant setting of colorectal cancer? Ann Oncol 19[Suppl 7]:vii184–186
Weigelt B, Bosma AJ, Hart AA, et al (2003) Marker genes for circulating tumor cells predict survival in metastasized breast cancer patients. Br J Cancer 88:1091–1094
Cristofanilli M, Budd GT, Ellis MJ et al (2004) Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med 351:781–791
Cristofanilli M, Hayes DF, Budd GT et al (2005) Circulating tumor cells: a novel prognostic factor for newly diagnosed metastatic breast cancer. J Clin Oncol 23:1420–1430
Hayes DF, Cristofanilli M, Budd GT et al (2006) Circulating tumor cells at each follow-up time point during therapy of metastatic breast cancer patients predict progression-free and overall survival. Clin Cancer Res 12:4218–4224
Smith BM, Slade MJ, English J et al (2000) Response of circulating tumor cells to systemic therapy in patients with metastatic breast cancer: comparison of quantitative polymerase chain reaction and immunocytochemical techniques. J Clin Oncol 18:1432–1439
Manhani AR, Manhani R, Soares HP et al (2001) CK-19 expression by RT-PCR in the peripheral blood of breast cancer patients correlates with response to chemotherapy. Breast Cancer Res Treat 66:249–254
Smerage JB, Hayes DF (2006) The measurement and therapeutic implications of circulating tumor cells in breast cancer. Br J Cancer 94:8–12
Xenidis N, Perraki M, Kafousi M et al (2006) Predictive and prognostic value of peripheral blood cytokeratin-19 mRNA-positive cells detected by real-time polymerase chain reaction in node-negative breast cancer patients. J Clin Oncol 24:3756–3762
Stathopoulou A, Vlachonikolis I, Mavroudis D et al (2002) Molecular detection of cytokeratin-19-positive cells in the peripheral blood of patients with operable breast cancer: evaluation of their prognostic significance. J Clin Oncol 20:3404–3412
Cohen SJ, Alpaugh RK, Gross S et al (2006) Isolation and characterization of circulating tumor cells in patients with metastatic colorectal cancer. Clin Colorectal Cancer 6:125–132
Lindemann F, Schlimok G, Dirschedl P et al (1992) Prognostic significance of micrometastatic tumor cells in bone marrow of colorectal cancer patients. Lancet 340:685–689
Vlems FA, Wobbes T, Punt CJ et al (2003) Detection and clinical relevance of tumor cells in blood and bone marrow of patients with colorectal cancer. Anticancer Res 23:523–530
Koch M, Kienle P, Kastrati D et al (2006) Prognostic impact of hematogenous tumor cell dissemination in patients with stage II colorectal cancer. Int J Cancer 118:3072–3077
Racila E, Euhus D, Weiss AJ et al (1998) Detection and characterization of carcinoma cells in the blood. Proc Natl Acad Sci USA 95:4589–4594
Vona G, Sabile A, Louha M et al (2000) Isolation by size of epithelial tumor cells: a new method for the immunomorphological and molecular characterization of circulating tumor cells. Am J Pathol 156:57–63
Ghossein RA, Bhattacharya S, Rosai J (1999) Molecular detection of micrometastases and circulating tumor cells in solid tumors. Clin Cancer Res 5:1950–1960
Bostick PJ, Chatterjee S, Chi DD et al (1998) Limitations of specific reverse-transcriptase polymerase chain reaction markers in the detection of metastases in the lymph nodes and blood of breast cancer patients. J Clin Oncol 16:2632–2640
Bessa X, Elizalde JI, Boix L et al (2001) Lack of prognostic influence of circulating tumor cells in peripheral blood of patients with colorectal cancer. Gastroenterology 120:1084–1092
Taniguchi T, Makino M, Suzuki K et al (2000) Prognostic significance of reverse transcriptase-polymerase chain reaction measurement of carcinoembryonic antigen mRNA levels in tumor drainage blood and peripheral blood of patients with colorectal carcinoma. Cancer 89:970–976
Balic M, Dandachi N, Hofmann G et al (2005) Comparison of two methods for enumerating circulating tumor cells in carcinoma patients. Cytometry B Clin Cytom 68:25–30
Allard WJ, Matera J, Miller MC et al (2004) Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res 10:6897–6904
Moreno JG, O’Hara SM, Gross S et al (2001) Changes in circulating carcinoma cells in patients with metastatic prostate cancer correlate with disease status. Urology 58:386–392
Rao CG, Chianese D, Doyle GV et al (2005) Expression of epithelial cell adhesion molecule in carcinoma cells present in blood and primary and metastatic tumors. Int J Oncol 27:49–57
Cristofanilli M (2006) Circulating tumor cells, disease progression, and survival in metastatic breast cancer. Semin Oncol 33[3 Suppl 9]:S9–14
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Garrigós, N., Gallego, J., Guillén-Ponce, C. et al. Circulating tumour cell analysis as an early marker for relapse in stage II and III colorectal cancer patients: a pilot study. Clin Transl Oncol 12, 142–147 (2010). https://doi.org/10.1007/S12094-010-0479-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/S12094-010-0479-7