Search tips
Search criteria 


Logo of molmedLink to Publisher's site
Mol Med. 1995 November; 1(7): 789–794.
PMCID: PMC2230007

Detection of circulating tumor cells in colorectal cancer by immunobead-PCR is a sensitive prognostic marker for relapse of disease.


BACKGROUND: Recurrent and metastatic carcinoma of the colorectum remains a major problem, with survival at 5 years post curative resection still only about 50%. Moreover, up to 30% of patients who present with early stage disease also relapse and die within 5 years, suggesting the presence of micrometastatic disease at diagnosis. One route of metastatic spread is via the blood stream, hence the detection of tumor cells in blood is likely to provide an important predictive tool with respect to relapse of disease. We have developed a sensitive molecular technique to identify tumor cells in blood using mutations in codon 12 of the K-ras gene as a marker. MATERIALS AND METHODS: Twenty-seven patients whose tumor carried a mutation in codon 12 of K-ras were studied for the presence of tumor cells in perioperative peripheral blood samples. Immunomagnetic beads, labeled with an epithelial-specific antibody, were used to harvest epithelial cells from blood. K-ras mutations were identified in this selected population using a polymerase chain reaction (PCR)-based analysis (immunobead-PCR). RESULTS: Circulating K-ras mutant cells were detected in 9 or 27 patients; seven of these nine patients have since died due to recurrent or metastatic disease. Mutant cells were not detected in 18 patients, and 16 or 18 have remained disease free (median follow-up: 16 months; range: 7-42 months). Kaplan-Meier analysis showed that detection of K-ras mutant cells in bloods was associated with significantly reduced disease-free survival (p = 0.0001). CONCLUSION: This study indicates that detection of circulating tumor cells perioperatively by immunobead-PCR provides a sensitive prognostic marker for recurrent and metastatic colorectal cancer.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (783K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Bos JL. ras oncogenes in human cancer: a review. Cancer Res. 1989 Sep 1;49(17):4682–4689. [PubMed]
  • Hardingham JE, Kotasek D, Farmer B, Butler RN, Mi JX, Sage RE, Dobrovic A. Immunobead-PCR: a technique for the detection of circulating tumor cells using immunomagnetic beads and the polymerase chain reaction. Cancer Res. 1993 Aug 1;53(15):3455–3458. [PubMed]
  • Fidler IJ. Cancer metastasis. Br Med Bull. 1991 Jan;47(1):157–177. [PubMed]
  • Liotta LA, Stetler-Stevenson WG. Tumor invasion and metastasis: an imbalance of positive and negative regulation. Cancer Res. 1991 Sep 15;51(18 Suppl):5054s–5059s. [PubMed]
  • Tarin D, Price JE, Kettlewell MG, Souter RG, Vass AC, Crossley B. Mechanisms of human tumor metastasis studied in patients with peritoneovenous shunts. Cancer Res. 1984 Aug;44(8):3584–3592. [PubMed]
  • Glaves D, Huben RP, Weiss L. Haematogenous dissemination of cells from human renal adenocarcinomas. Br J Cancer. 1988 Jan;57(1):32–35. [PMC free article] [PubMed]
  • Leather AJ, Gallegos NC, Kocjan G, Savage F, Smales CS, Hu W, Boulos PB, Northover JM, Phillips RK. Detection and enumeration of circulating tumour cells in colorectal cancer. Br J Surg. 1993 Jun;80(6):777–780. [PubMed]
  • Smith B, Selby P, Southgate J, Pittman K, Bradley C, Blair GE. Detection of melanoma cells in peripheral blood by means of reverse transcriptase and polymerase chain reaction. Lancet. 1991 Nov 16;338(8777):1227–1229. [PubMed]
  • Mattano LA, Jr, Moss TJ, Emerson SG. Sensitive detection of rare circulating neuroblastoma cells by the reverse transcriptase-polymerase chain reaction. Cancer Res. 1992 Sep 1;52(17):4701–4705. [PubMed]
  • Seiden MV, Kantoff PW, Krithivas K, Propert K, Bryant M, Haltom E, Gaynes L, Kaplan I, Bubley G, DeWolf W, et al. Detection of circulating tumor cells in men with localized prostate cancer. J Clin Oncol. 1994 Dec;12(12):2634–2639. [PubMed]
  • Datta YH, Adams PT, Drobyski WR, Ethier SP, Terry VH, Roth MS. Sensitive detection of occult breast cancer by the reverse-transcriptase polymerase chain reaction. J Clin Oncol. 1994 Mar;12(3):475–482. [PubMed]
  • Brown DC, Purushotham AD, Birnie GD, George WD. Detection of intraoperative tumor cell dissemination in patients with breast cancer by use of reverse transcription and polymerase chain reaction. Surgery. 1995 Jan;117(1):95–101. [PubMed]
  • Mayhew E, Glaves D. Quantitation of tumorigenic disseminating and arrested cancer cells. Br J Cancer. 1984 Aug;50(2):159–166. [PMC free article] [PubMed]
  • Fidler IJ. Metastasis: guantitative analysis of distribution and fate of tumor embolilabeled with 125 I-5-iodo-2'-deoxyuridine. J Natl Cancer Inst. 1970 Oct;45(4):773–782. [PubMed]
  • Glaves D. Correlation between circulating cancer cells and incidence of metastases. Br J Cancer. 1983 Nov;48(5):665–673. [PMC free article] [PubMed]
  • Riethmüller G, Schneider-Gädicke E, Schlimok G, Schmiegel W, Raab R, Höffken K, Gruber R, Pichlmaier H, Hirche H, Pichlmayr R, et al. Randomised trial of monoclonal antibody for adjuvant therapy of resected Dukes' C colorectal carcinoma. German Cancer Aid 17-1A Study Group. Lancet. 1994 May 14;343(8907):1177–1183. [PubMed]

Articles from Molecular Medicine are provided here courtesy of The Feinstein Institute for Medical Research at North Shore LIJ