Skip to main content
SpringerLink
Log in

Lymph node micrometastases do not predict relapse in stage II colon cancer

  • Original Articles
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background: Over one third of patients with stage II colonic adenocarcinoma experience tumor recurrence. Because effective adjuvant therapy is now available, it is important to identify subsets of patients at higher risk for relapse who may benefit from early treatment. Immunohistochemistry has been used to detect microscopic metastases in histologically uninvolved mesenteric lymph nodes, but the prognostic significance of minimal nodal involvement has not been established.

Methods: Hematoxylin and eosin (H&E)-stained recuts of 900 mesenteric lymph nodes from 55 patients (range, 2–47; mean, 16.4 nodes per case) with resected pT3 or pT4, N0, M0 (TNM stage II) colonic adenocarcinomas were re-examined for the presence of metastases and then stained immunohistochemically for keratin using the AE1:AE3 antibody. Twenty-seven patients did not experience recurrence of tumor within 5 years following resection (no evidence of disease [NED]); 28 patients relapsed during the same time frame. Lymph nodes from 10 patients having colonic resections for nonneoplastic disorders also were stained as controls. Keratin-positive cells and cell clusters were quantified in the lymph nodes, and comparisons were made between patients with and without tumor relapse.

Results: In the relapse group, four patients had positive nodes already identified on the H&E-stained recuts and had to be excluded from further analysis. Sixteen additional patients had keratin-positive cells; thus, 16 of 24 (67%) had micrometastases. In the NED group, one patient had a positive node on H&E staining and 22 additional patients had keratin-positive cells, so 22 of 26 (84%) patients had micrometastases. In the patients who had micrometastases, there was a mean of 3.5 and 4.6 positive nodes in the relapse and NED groups, respectively, and a mean of 11.3 and 12.4 keratin-positive cells or clusters in the relapse and NED groups, respectively. No keratin-positive cells were found in the 1 to 21 (mean, 9.1) nodes per case studied in the control patients.

Conclusions: Micrometastases to histologically uninvolved mesenteric lymph nodes commonly are detected in patients with pT3 or pT4 colonic adenocarcinomas on recuts stained immunohistochemically for keratin. Nodal micrometastases detected by immunohistochemical staining are not useful for identifying stage II patients at higher risk for relapse.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Cohen AM, Minsky BD, Schilsky RL. Cancer of the colon. In: DeVita VT, Hellman S, Rosenberg SA.Cancer: Principles and Practice of Oncology, 5th ed. New York: Lippincott-Raven, 1997:1144–96.

    Google Scholar 

  2. Eisenberg B, Decosse JJ, Harford F, Michalek J. Carcinoma of the colon and rectum: the natural history reviewed in 1704 patients.Cancer 1982;49:1131–4.

    Article  PubMed  CAS  Google Scholar 

  3. Adell G, Boeryd B, Franlund B, Sjodahi R, Hakansson L. Occurrence and prognostic importance of micrometastases in regional lymph nodes in Dukes’ B colorectal carcinoma: an immunohistochemical study.Eur J Surg 1996;162:637–42.

    PubMed  CAS  Google Scholar 

  4. Cutait R, Alves VAF, Lopes LC, et al. Restaging of colorectal cancer based on the identification of lymph node micrometastases through immunoperoxidase staining of CEA and cytokeratins.Dis Colon Rectum 1991;34:917–20.

    Article  PubMed  CAS  Google Scholar 

  5. Greenson JK, Isenhart CE, Rice R, Mojzisik C, Houchens D, Martin EW. Identification of occult micrometastases in pericolic lymph nodes of Dukes’ B colorectal cancer patients using monoclonal antibodies against cytokeratin and CC49.Cancer 1994;73:563–9.

    Article  PubMed  CAS  Google Scholar 

  6. Haboubi NY, Clark P, Kaftan SM, Schofield PF. The importance of combining xylene clearance and immunohistochemistry in the accurate staging of colorectal carcinoma.J R Soc Med 1992;85:386–8.

    PubMed  CAS  Google Scholar 

  7. Jeffers MD, O’Dowd GM, Mulcahy H, Stagg M, O’Donoghue DP, Toner M. The prognostic significance of immunohistochemically detected lymph node micrometastases in colorectal carcinoma.J Pathol 1994;172:183–7.

    Article  PubMed  CAS  Google Scholar 

  8. Makin CA, Bobrow LG, Nicholls RJ. Can immunohistology improve detection of lymph node metastases in large bowel cancer?Dis Colon Rectum 1989;32:99–102.

    Article  PubMed  CAS  Google Scholar 

  9. Broll R, Schauer V, Schimmelpennig H, et al. Prognostic relevance of occult tumor cells in lymph nodes of colorectal carcinomas.Dis Col Rectum 1997;40:1465–71.

    Article  CAS  Google Scholar 

  10. Franke WW, Moll R. Cytoskeletal components of lymphoid organs.Differentiation 1987;36:145–63.

    Article  PubMed  CAS  Google Scholar 

  11. Iuzzolino P, Bontempini L. Keratin immunoreactivity in extrafollicular reticular cells of the lymph node. Correspondence and Corrections.Am J Clin Pathol 1989;91:239–40.

    PubMed  CAS  Google Scholar 

  12. Kovarik J, Rejthar A, Lauerova L, Vojtesek B, Bartkova J. Monoclonal antibodies against individual cytokeratins in the detection of metastatic spread.Int J Cancer 1988; 3(Suppl):50–5.

    Article  CAS  Google Scholar 

  13. Pickren JW. Significance of occult metastases. A study of breast cancer.Cancer 1961;14:1266–71.

    Article  PubMed  CAS  Google Scholar 

  14. Crowson M, Hockey MS, Newman J, Stokes H, Macdonald F, Fielding JW. An immunocytochemical study of carcinoembryonic antigen (CEA) expression in colorectal tumours and their metastases using a monoclonal antibody.Br J Surg 1984;71:376.

    Article  Google Scholar 

  15. Davidson BR, Sams VR, Styles I, Deane C, Boulos PB. Detection of occult nodal metastases in patients with colorectal carcinoma.Cancer 1990;65:967–70.

    Article  PubMed  CAS  Google Scholar 

  16. Nakopoulou L, Zinozi M, Theodoropoulos G, Papacharalampous N. Carcinoembryonic antigen detection by immunocytochemical methods in carcinoma of the colon and stomach.Dis Colon Rectum 1983;26:269–74.

    Article  PubMed  CAS  Google Scholar 

  17. O’Brien MI, Zamcheck N, Burke B, Kirkham SE, Saravis CA, Gottlieb LS. Immunocytochemical localization of carcinoembryonic antigen in benign and malignant colorectal tissues.Am J Clin Pathol 1981;75:283–90.

    PubMed  CAS  Google Scholar 

  18. Listrom MB, Dalton LW. Comparison of keratin monoclonal antibodies MAK-6, AE1:AE3, and CAM 5.2.Am J Clin Pathol 1987;88:297–301.

    PubMed  CAS  Google Scholar 

  19. Moll R, Franke WW, Schiller DL, Geiger B, Krepler R. The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells.Cell 1982;31:11–24.

    Article  PubMed  CAS  Google Scholar 

  20. Schlimok G, Funke I, Bock B, Schweiberer B, Witte I, Riethmuller G. Epithelial tumor cells in bone marrow of patients with colorectal cancer: immunocytochemical detection, phenotypic characterization, and prognostic significance.J Clin Oncol 1990;8:831–7.

    PubMed  CAS  Google Scholar 

  21. Brodsky IT, Richard GK, Cohen AM, Minsky BD. Variables correlated with the risk of lymph node metastasis in early rectal cancer.Cancer 1992;69:322–26.

    Article  PubMed  CAS  Google Scholar 

  22. Chapuis PH, Dent OF, Fisher R, Newland RC, Pheils MT, Smyth E, Colquhoun K. A multivariate analysis of clinical and pathological variables in prognosis after resection of large bowel cancer.Br J Surg 1985;72:698–702.

    Article  PubMed  CAS  Google Scholar 

  23. Fielding LP, Fenoglio-Preiser CM, Freedman LS. The future of prognostic factors in outcome prediction for patients with cancer.Cancer 1992;70:2367–77.

    Article  PubMed  CAS  Google Scholar 

  24. Cawthorn SI, Gibbs NM, Marks CG. Clearance technique for the detection of lymph nodes in colorectal cancer.Br J Surg 1986;73:58–60.

    Article  PubMed  CAS  Google Scholar 

  25. Hase K, Kochizuki H, Koike M, et al. A study on prognostic value of tumor budding in patients with rectal cancer.Jpn J Gastroenterol Surg 1992;25:2765–72.

    Google Scholar 

  26. Takizawa K. Histopathological study of rectal cancer with special reference to tumor histology and cellular stromal reaction.J Jpn Soc Coloproctol 1989;42:190–201.

    Google Scholar 

  27. Liefers GJ, Cleton-Jansen AM, VandeVelde CJH, Hermans J, van Krieken HJM, Cornelisse CJ, Tollenaar R. Micrometastases and survival in stage II colorectal cancer.N Engl J Med 1998;339:223–8.

    Article  PubMed  CAS  Google Scholar 

  28. Hayashi N, Ito I, Yanagisawa A, Kato Y, Nakamori S, Imaoka S, Watanabe H, Ogawa M, Nakamura Y. Genetic diagnosis of lymphnode metastasis in colorectal cancer.Lancet 1995;345:1257–9; commentary, p. 1255.

    Article  PubMed  CAS  Google Scholar 

  29. Burchill SA, Bradbury MF, Pittman K, Southgate I, Smith B, Selby P. Detection of epithelial cancer cells in peripheral blood by reverse transcriptase-polymerase chain reaction.Br J Cancer 1995;71:278–81.

    PubMed  CAS  Google Scholar 

  30. Fidler IJ, Radinsky R. Genetic control of cancer metastasis.J Natl Cancer Inst 1990;82:166–8.

    Article  PubMed  CAS  Google Scholar 

  31. Kerbel RS. Towards an understanding of the molecular basis of the metastatic phenotype.Invasion Metastasis 1989;9:329–33.

    PubMed  CAS  Google Scholar 

  32. Radinsky R. Growth factors and their receptors in metastasis.Semin Cancer Biol 1991;2:169–77.

    PubMed  CAS  Google Scholar 

  33. Wright IA, Egan SE, Greenberg AH. Genetic regulation of metastatic progression.AntiCancer Res 1990;10:1247–56.

    PubMed  CAS  Google Scholar 

  34. Fisher ER, Turnbull RB. The cytologic demonstration and significance of tumour cells in the mesenteric venous blood in patients with colorectal carcinoma.Surg Gynecol Obstet 1955;100:102.

    PubMed  CAS  Google Scholar 

  35. Griffiths ID, McKinna IA, Rowbotham HD, Tsolakidis P, Salsbury AL. Carcinoma of the colon and rectum: circulating malignant cells and five-year survival.Cancer 1973;31:226–36.

    Article  PubMed  CAS  Google Scholar 

  36. Salsbury AL, McKinna IA, Griffiths ID, Morgan CN. Circulating cancer cells during excision of carcinoma of the rectum and colon with high ligation of the inferior mesenteric vein.Surg Gynecol Obstet 1965;120:1266.

    PubMed  CAS  Google Scholar 

  37. Kitadai Y, Bucana CD, Ellis LM, Anzai H, Tahara E, Fidler IJ. In situ mRNA hybridization technique for analysis of metastasis-related genes in human colon carcinoma cells.Am J Pathol 1995;147:1238–47.

    PubMed  CAS  Google Scholar 

  38. Liotta LA, Stetler-Stevenson WG. Tumor invasion and metastasis: an imbalance of positive and negative regulation.Cancer Res 1991;51(Suppl):5054–9.

    Google Scholar 

  39. Radinsky R, Risin S, Fan D, Dong Z, Bielenberg D, Bucana CD, Fidler IJ. Level and function of epidermal growth factor receptor predict the metastatic potential of human colon carcinoma cells.Clin Cancer Res 1995;1:19–31.

    PubMed  CAS  Google Scholar 

  40. Oberg A, Stenling R, Tavelin B, Lindmark G. Are lymph node micrometastases of any clinical significance in Dukes stages A and B colorectal cancer?Dis Colon Rectum 1998;41:1244–9.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. From the Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY

    David S. Klimstra MD

  2. Colorectal Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, 10021, New York, NY

    Jorg Tschmelitsch MD & Alfred M. Cohen MD

Authors
  1. Jorg Tschmelitsch MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David S. Klimstra MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alfred M. Cohen MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alfred M. Cohen MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tschmelitsch, J., Klimstra, D.S. & Cohen, A.M. Lymph node micrometastases do not predict relapse in stage II colon cancer. Ann Surg Oncol 7, 601–608 (2000). https://doi.org/10.1007/BF02725340

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02725340

Key Word

Search

Navigation