Annals of Surgical Oncology

, Volume 14, Issue 3, pp 1092–1098 | Cite as

Detection of Carcinoembryonic Antigen Messenger RNA-Expressing Cells in Peripheral Blood 7 Days After Curative Surgery is a Novel Prognostic Factor in Colorectal Cancer

  • Sotaro Sadahiro
  • Toshiyuki Suzuki
  • Yuji Maeda
  • Satoshi Yurimoto
  • Seiei Yasuda
  • Hiroyasu Makuuchi
  • Akemi Kamijo
  • Chieko Murayama
Article

Abstract

Background

The significance of detection of circulating cancer cells in blood during surgery in patients with colorectal cancer (CRC) remains controversial. Experimental study revealed that the cancer cells injected from the vein disappeared completely until 7 days. The aim of this study was to clarify that the detection of circulating cancer cells in blood taken later than 7 days after curative surgery may be a prognostic factor.

Methods

Two hundred consecutive patients with CRC who underwent potentially curative surgery were the subjects. Peripheral blood was collected between 7 and 10 days after resection. Cancer cells were detected using reverse transcriptase-polymerase chain reaction targeting carcinoembryonic antigen (CEA) messenger RNA (mRNA). The median follow-up period was 52 months (range: 34–69 months).

Results

The overall positive incidence of CEA mRNA was 22%. Detection of CEA mRNA was not significantly related to conventional clinicopathological findings. Recurrence has been confirmed in 55 patients (28%). The recurrence rate was significantly higher in patients with rectal cancer, deep penetration, lymph node metastasis, preoperative chemoradiotherapy and positive CEA mRNA. The CEA mRNA positive patients showed significantly poorer disease free survival (DFS) and overall survival (OS) than the negative patients (DFS, P = 0.007; OS, P = 0.04). Multivariate analysis revealed that the positive expression of CEA mRNA (P < 0.01) as well as the tumor location and TNM stage classification was identified as the significant risk factors for recurrence.

Conclusions

Detection of CEA mRNA expressing cells in peripheral blood 7 days after curative surgery is a novel independent factor predicting recurrence in patients with CRC.

Keywords

Colorectal cancer Carcinoembryonic antigen (CEA) Circulating tumor cells Reverse transcriptase-polymerase chain reaction (RT-PCR) 

References

  1. 1.
    Safi F, Beyer HG. The value of follow-up after curative surgery of colorectal carcinoma. Cancer Detect Prev 1993; 17:417–424PubMedGoogle Scholar
  2. 2.
    Castells A, Essa X, Daniels M, et al. Value of postoperative surveillance after radical surgery for colorectal cancer: Results of a cohort study. Dis Colon Rectum 1998; 41:714–724PubMedCrossRefGoogle Scholar
  3. 3.
    Goldberg RM, Fleming TR, Tangen CM, et al. Surgery for recurrent colon cancer: Strategies for identifying resectable recurrence and success rates after resection. Ann Intern Med 1998; 129:27–35PubMedGoogle Scholar
  4. 4.
    Sadahiro S, Suzuki T, Ishikawa K, et al. Estimation of the time of pulmonary metastasis in colorectal cancer patients with isolated synchronous liver metastasis. Jpn J Clin Oncol 2005; 35:18–22PubMedCrossRefGoogle Scholar
  5. 5.
    Gerhard M, Juhl H, Kalthoff H, Schreiber HW, Wagener C, Neumaier M. Specific detection of carcinoembryonic antigen-expressing tumor cells in bone marrow aspirates by polymerase chain reaction. J Clin Oncol 1994; 12:725–729PubMedGoogle Scholar
  6. 6.
    Burchill SA, Bradbury MF, Pittman K, Southgate J, Smith B, Selby P. Detection of epithelial cancer cells in peripheral blood by reverse transcriptase-polymerase chain reaction. Br J Cancer 1995; 71:278–281PubMedGoogle Scholar
  7. 7.
    Jonas S, Windeatt S, Boateng AO, Fordy C, Allen-Mersh TG. Identification of carcinoembryonic antigen producing cells circulating in the blood of patients with colorectal carcinoma by reverse transcriptase chain reaction. Gut 1996; 39:717–721PubMedGoogle Scholar
  8. 8.
    Mori M, Mimori K, Ueno H, et al. Clinical significance of molecular detection of carcinoma cells in lymph nodes and peripheral blood by reverse transcription-polymerase chain reaction in patients with gastrointestinal or breast carcinomas. J Clin Oncol 1998; 16:128–132PubMedGoogle Scholar
  9. 9.
    Weitz J, Kienle P, Lacroix J, et al. Dissemination of tumor cells in patients undergoing surgery for colorectal cancer. Clin Cancer Res 1998; 4:343–348PubMedGoogle Scholar
  10. 10.
    Guller U, Zajac P, Schnider A, et al. Disseminated single tumor cells as detected by real-time quantitative polymerase chain reaction represent a prognostic factor in patients undergoing surgery for colorectal cancer. Ann Surg 2002; 236:768–776PubMedCrossRefGoogle Scholar
  11. 11.
    Taniguchi T, Makino M, Suzuki K, Kaibara N. 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 2000; 89:970–976PubMedCrossRefGoogle Scholar
  12. 12.
    Weitz J, Koch M, Kienle P, et al. Detection of hematogenic tumor cell dissemination in patients undergoing resection of liver metastases of colorectal cancer. Ann Surg 2000; 232:66–72PubMedCrossRefGoogle Scholar
  13. 13.
    Yamaguchi K, Takagi Y, Aoki S, Futamura M, Saji S. Significant detection of circulating cancer cells in the blood by reverse transcriptase-polymerase chain reaction during colorectal cancer resection. Ann Surg 2000; 232:58–65PubMedCrossRefGoogle Scholar
  14. 14.
    Bessa X, Elizalde JI, Boix L, et al. Lack of prognostic influence of circulating tumor cells in peripheral blood of patients with colorectal cancer. Gastroenterol 2001; 120:1084–1092CrossRefGoogle Scholar
  15. 15.
    Fujita S, Kudo N, Akasu T, Moriya Y. Detection of cytokeratin 19 and 20 mRNA in peripheral and mesenteric blood from colorectal cancer patients and their prognosis. Int J Colorectal Dis 2001; 16:141–146PubMedCrossRefGoogle Scholar
  16. 16.
    Sadahiro S, Suzuki T, Tokunaga N, et al. Detection of tumor cells in the portal and peripheral blood of patients with colorectal carcinoma using competitive reverse transcriptase-polymerase chain reaction. Cancer 2001; 92:1251–1258PubMedCrossRefGoogle Scholar
  17. 17.
    Ito S, Nakanishi H, Hirai T, et al. Quantitative detection of CEA expressing free tumor cells in the peripheral blood of colorectal cancer patients during surgery with real-time RT-PCR on a LightCycler. Cancer Lett 2002; 183:195–203PubMedCrossRefGoogle Scholar
  18. 18.
    Bessa X, Pinol V, Castellvi-Bel S, et al. Prognostic value of postoperative detection of blood circulating tumor cells in patients with colorectal cancer operated on for cure. Ann Surg 2003; 237:368–375PubMedCrossRefGoogle Scholar
  19. 19.
    Vlems FA, Diepstra JHS, Cornelissen IMHA, et al. Limitations of cytokeratin 20 RT-PCR to detect dissemination tumour cells in blood and bone marrow of patients with colorectal cancer: expression in controls and downregulation in tumour tissue. J Clin Pathol Mol Pathol 2002; 55:156–163CrossRefGoogle Scholar
  20. 20.
    Sadahiro S, Suzuki T, Ishikawa K, et al. Detection of carcinoembryonic antigen messenger RNA-expressing cells in portal and peripheral blood during surgery does not influence relapse in colorectal cancer. Ann Surg Oncol 2005; 12:988–994PubMedCrossRefGoogle Scholar
  21. 21.
    Patel H, Marer NL, Wharton RQ, et al. Clearance of circulating tumor cells after excision of primary colorectal cancer. Ann Surg 2002; 235:226–231PubMedCrossRefGoogle Scholar
  22. 22.
    Fidler IJ. Metastasis: Quantitative analysis of distribution and fate of tumor emboli labeled with 125 I-5-iodo−2′-deoxyuridine. J Natl Cancer Inst 1970; 45:773–782PubMedGoogle Scholar
  23. 23.
    Kaplan EL, Meier P. Nonparametric estimation of incomplete observations. J Am Stat Assoc 1958; 53:457–481CrossRefGoogle Scholar
  24. 24.
    Cox DR. Regression models and life tables. J R Stat Soc Br 1972; 34:187–220Google Scholar
  25. 25.
    Tien YW, Lee PH, Wang SM, Hsu SM, Chang KJ. Simultaneous detection of colonic epithelial cells in portal venous and peripheral blood during colorectal cancer surgery. Dis Colon Rectum 2002; 45:23–29PubMedCrossRefGoogle Scholar
  26. 26.
    Miyazono F, Natsugoe S, Takao S, et al. Surgical maneuvers enhance molecular detection of circulating tumor cells during gastric cancer surgery. Ann Surg 2001; 233:189–194PubMedCrossRefGoogle Scholar
  27. 27.
    Koch M, Weitz J, Kienle P, et al. Comparative analysis of tumor cell dissemination in mesenteric, central, and peripheral venous blood in patients with colorectal cancer. Arch Surg 2001; 136:85–89PubMedCrossRefGoogle Scholar
  28. 28.
    Zhang XW, Yang HY, Fan P, Yang L, Chen GY. Detection of micrometastasis in peripheral blood by multi-sampling in patients with colorectal cancer. World J Gastroenterol 2005; 11:436–438PubMedGoogle Scholar
  29. 29.
    Greene FL, Balch CM, Fleming ID, et al. (eds). (2002) AJCC manual for staging of cancer, 6th edn. Berlin Heidelberg New York:SpringerGoogle Scholar

Copyright information

© Society of Surgical Oncology 2007

Authors and Affiliations

  • Sotaro Sadahiro
    • 1
    • 3
  • Toshiyuki Suzuki
    • 1
  • Yuji Maeda
    • 1
  • Satoshi Yurimoto
    • 1
  • Seiei Yasuda
    • 1
  • Hiroyasu Makuuchi
    • 1
  • Akemi Kamijo
    • 1
  • Chieko Murayama
    • 2
  1. 1.Department of SurgeryTokai University School of MedicineKanagawaJapan
  2. 2.Department of Clinical PharmacologyTokai University School of MedicineKanagawaJapan
  3. 3.Department of SurgeryTokai UniversityKanagawaJapan

Personalised recommendations