Skip to main content

Advertisement

Log in

Lymph Node Harvest in Colon Cancer: Influence of Microsatellite Instability and Proximal Tumor Location

  • Published:
World Journal of Surgery Aims and scope Submit manuscript

Abstract

Background

At least 12 harvested lymph nodes are recommended for proper staging of colon cancer. The effect of tumor-related factors associated with lymph node harvest is not well understood as data are lacking. We investigated tumor-related factors in relation to the number of lymph nodes harvested.

Methods

Patient and tumor characteristics were investigated in relation to harvested lymph nodes (LN ≥ 12), number of metastatic nodes, LN ratio (LNR), and prognosis with univariate and multivariate analyses.

Results

An LN harvest ≥12 nodes was achieved in 36% of the patients. Having <12 nodes harvested was not associated with increased risk for locoregional recurrence, distant metastasis, or decreased survival. Tumor size >5 cm, microsatellite instability (MSI), and proximal tumor location predicted a harvest of LN ≥ 12. The highest rate (54%) of LN ≥ 12 was found for MSI cancers [odds ratio (OR) 2.9, 95% confidence interval (CI) 1.3–6.5; P = 0.011]. Multivariate analysis identified a proximal location as an independent factor of LN ≥ 12 (adjusted OR 3.5, 95% CI 1.5–8.2; P = 0.003), with MSI an independent factor in stage II to III colon cancer (adjusted OR 2.6, 95% CI 1.1–6.0; P = 0.026). To determine the best prognosticator, LNR was the only significant factor in the multivariate analysis (Cox proportional hazards) with a hazard ratio (HR) of 2.9 (95% CI 1.1–7.8; P = 0.038) for LNR 0.01–0.17 and an HR of 5.8 (95% CI 2.5–13.1; P < 0.001).

Conclusions

Proximal tumor location and microsatellite instability are associated with a higher number of lymph nodes harvested, pointing to possible underlying genetic and immunologic mechanisms. The LNR is an independent prognostic variable for colon cancer.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Chang GJ, Rodriguez-Bigas MA, Skibber JM et al (2007) Lymph node evaluation and survival after curative resection of colon cancer: systematic review. J Natl Cancer Inst 99:433–441

    Article  PubMed  Google Scholar 

  2. Wright FC, Law CH, Berry S et al (2009) Clinically important aspects of lymph node assessment in colon cancer. J Surg Oncol 99:248–255

    Article  PubMed  Google Scholar 

  3. Cianchi F, Palomba A, Boddi V et al (2002) Lymph node recovery from colorectal tumor specimens: recommendation for a minimum number of lymph nodes to be examined. World J Surg 26:384–389

    Article  PubMed  Google Scholar 

  4. Baxter NN (2009) Is lymph node count an ideal quality indicator for cancer care? J Surg Oncol 99:265–268

    Article  PubMed  Google Scholar 

  5. Simunovic M, Baxter NN (2007) Lymph node counts in colon cancer surgery: lessons for users of quality indicators. JAMA 298:2194–2195

    Article  CAS  PubMed  Google Scholar 

  6. Ricciardi R, Baxter NN (2007) Association versus causation versus quality improvement: setting benchmarks for lymph node evaluation in colon cancer. J Natl Cancer Inst 99:414–415

    Article  PubMed  Google Scholar 

  7. Wang J, Kulaylat M, Rockette H et al (2009) Should total number of lymph nodes be used as a quality of care measure for stage III colon cancer? Ann Surg 249:559–563

    Article  PubMed  Google Scholar 

  8. Wong SL, Ji H, Hollenbeck BK et al (2007) Hospital lymph node examination rates and survival after resection for colon cancer. JAMA 298:2149–2154

    Article  CAS  PubMed  Google Scholar 

  9. Shaw A, Collins EE, Fakis A et al (2008) Colorectal surgeons and biomedical scientists improve lymph node harvest in colorectal cancer. Tech Coloproctol 12:295–298

    Article  CAS  PubMed  Google Scholar 

  10. Evans MD, Barton K, Rees A et al (2008) The impact of surgeon and pathologist on lymph node retrieval in colorectal cancer and its impact on survival for patients with Dukes’ stage B disease. Colorectal Dis 10:157–164

    CAS  PubMed  Google Scholar 

  11. Wright FC, Gagliardi AR, Law CH et al (2008) A randomized controlled trial to improve lymph node assessment in stage II colon cancer. Arch Surg 143:1050–1055; discussion 1055

    Article  PubMed  Google Scholar 

  12. Søreide K, Janssen EA, Søiland H et al (2006) Microsatellite instability in colorectal cancer. Br J Surg 93:395–406

    Article  PubMed  CAS  Google Scholar 

  13. Søreide K, Slewa A, Stokkeland PJ et al (2009) Microsatellite instability and DNA ploidy in colorectal cancer: potential implications for patients undergoing systematic surveillance after resection. Cancer 115:271–282

    Article  PubMed  CAS  Google Scholar 

  14. Kørner H, Søreide K, Stokkeland PJ et al (2005) Systematic follow-up after curative surgery for colorectal cancer in Norway: a population-based audit of effectiveness, costs, and compliance. J Gastrointest Surg 9:320–328

    Article  PubMed  Google Scholar 

  15. Bjugn R, Dirdal HU (2001) Colorectal cancer—experiences with the use of standardized forms for reporting pathologic–anatomic data. Tidsskr Nor Laegeforen 121:1697–1701

    CAS  PubMed  Google Scholar 

  16. Wang J, Hassett JM, Dayton MT et al (2008) Lymph node ratio: role in the staging of node-positive colon cancer. Ann Surg Oncol 15:1600–1608

    Article  PubMed  Google Scholar 

  17. De Ridder M, Vinh-Hung V, Van Nieuwenhove Y et al (2006) Prognostic value of the lymph node ratio in node positive colon cancer. Gut 55:1681

    Article  PubMed  Google Scholar 

  18. Rosenberg R, Friederichs J, Schuster T et al (2008) Prognosis of patients with colorectal cancer is associated with lymph node ratio: a single-center analysis of 3,026 patients over a 25-year time period. Ann Surg 248:968–978

    Article  PubMed  Google Scholar 

  19. Kørner H, Søreide K, Stokkeland PJ et al (2007) Diagnostic accuracy of serum-carcinoembryonic antigen in recurrent colorectal cancer: a receiver operating characteristic curve analysis. Ann Surg Oncol 14:417–423

    Article  PubMed  Google Scholar 

  20. Baxter NN, Morris AM, Rothenberger DA et al (2005) Impact of preoperative radiation for rectal cancer on subsequent lymph node evaluation: a population-based analysis. Int J Radiat Oncol Biol Phys 61:426–431

    PubMed  Google Scholar 

  21. Buhard O, Suraweera N, Lectard A et al (2004) Quasimonomorphic mononucleotide repeats for high-level microsatellite instability analysis. Dis Markers 20:251–257

    PubMed  Google Scholar 

  22. Suraweera N, Duval A, Reperant M et al (2002) Evaluation of tumor microsatellite instability using five quasimonomorphic mononucleotide repeats and pentaplex PCR. Gastroenterology 123:1804–1811

    Article  CAS  PubMed  Google Scholar 

  23. Lindor NM, Smalley R, Barker M et al (2006) Ascending the learning curve: MSI testing experience of a six-laboratory consortium. Cancer Biomark 2:5–9

    CAS  PubMed  Google Scholar 

  24. Søreide K (2007) Molecular testing for microsatellite instability and DNA mismatch repair defects in hereditary and sporadic colorectal cancers: ready for prime time? Tumour Biol 28:290–300

    Article  PubMed  CAS  Google Scholar 

  25. Pinkowish MD (2009) Lymph node evaluation as a colon cancer quality measure. CA Cancer J Clin 59:2–4

    Article  PubMed  Google Scholar 

  26. Hsu CW, Lin CH, Wang JH et al (2009) Factors that influence 12 or more harvested lymph nodes in early-stage colorectal cancer. World J Surg 33:333–339

    Article  PubMed  Google Scholar 

  27. Baxter NN, Virnig DJ, Rothenberger DA et al (2005) Lymph node evaluation in colorectal cancer patients: a population-based study. J Natl Cancer Inst 97:219–225

    Article  PubMed  Google Scholar 

  28. Bui L, Rempel E, Reeson D et al (2006) Lymph node counts, rates of positive lymph nodes, and patient survival for colon cancer surgery in Ontario, Canada: a population-based study. J Surg Oncol 93:439–445

    Article  PubMed  Google Scholar 

  29. Wright FC, Law CH, Last L et al (2003) Lymph node retrieval and assessment in stage II colorectal cancer: a population-based study. Ann Surg Oncol 10:903–909

    Article  CAS  PubMed  Google Scholar 

  30. Tekkis PP, Smith JJ, Heriot AG et al (2006) A national study on lymph node retrieval in resectional surgery for colorectal cancer. Dis Colon Rectum 49:1673–1683

    Article  PubMed  Google Scholar 

  31. Søreide K (2009) Receiver-operating characteristic curve analysis in diagnostic, prognostic and predictive biomarker research. J Clin Pathol 62:1–5

    Article  PubMed  Google Scholar 

  32. Tsai HL, Lu CY, Hsieh JS et al (2007) The prognostic significance of total lymph node harvest in patients with T2–4N0M0 colorectal cancer. J Gastrointest Surg 11:660–665

    Article  PubMed  Google Scholar 

  33. Vather R, Sammour T, Kahokehr A et al (2009) Lymph node evaluation and long-term survival in stage II and stage III colon cancer: a national study. Ann Surg Oncol 16:585–593

    Article  PubMed  Google Scholar 

  34. Søreide K, Nedrebo BS, Knapp JC et al (2009) Evolving molecular classification by genomic and proteomic biomarkers in colorectal cancer: potential implications for the surgical oncologist. Surg Oncol 18:31–50

    Article  PubMed  Google Scholar 

  35. Phillips SM, Banerjea A, Feakins R et al (2004) Tumour-infiltrating lymphocytes in colorectal cancer with microsatellite instability are activated and cytotoxic. Br J Surg 91:469–475

    Article  CAS  PubMed  Google Scholar 

  36. Alexander J, Watanabe T, Wu TT et al (2001) Histopathological identification of colon cancer with microsatellite instability. Am J Pathol 158:527–535

    CAS  PubMed  Google Scholar 

  37. Smyrk TC, Watson P, Kaul K et al (2001) Tumor-infiltrating lymphocytes are a marker for microsatellite instability in colorectal carcinoma. Cancer 91:2417–2422

    Article  CAS  PubMed  Google Scholar 

  38. Pages F, Berger A, Camus M et al (2005) Effector memory T cells, early metastasis, and survival in colorectal cancer. N Engl J Med 353:2654–2666

    Article  CAS  PubMed  Google Scholar 

  39. Galon J, Costes A, Sanchez-Cabo F et al (2006) Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 313:1960–1964

    Article  CAS  PubMed  Google Scholar 

  40. Johnson PM, Porter GA, Ricciardi R et al (2006) Increasing negative lymph node count is independently associated with improved long-term survival in stage IIIB and IIIC colon cancer. J Clin Oncol 24:3570–3575

    Article  PubMed  Google Scholar 

  41. George S, Primrose J, Talbot R et al (2006) Will Rogers revisited: prospective observational study of survival of 3592 patients with colorectal cancer according to number of nodes examined by pathologists. Br J Cancer 95:841–847

    Article  CAS  PubMed  Google Scholar 

  42. Norwood MG, Sutton A, West K, et al (2009) Lymph node retrieval in colorectal cancer resection specimens: national standards are achievable, and low numbers are associated with reduced survival. Colorectal Dis Feb 4 [Epub ahead of print]

  43. Titu LV, Tweedle E, Rooney PS (2008) High tie of the inferior mesenteric artery in curative surgery for left colonic and rectal cancers: a systematic review. Dig Surg 25:148–157

    Article  CAS  PubMed  Google Scholar 

  44. Lemmens VE, van Lijnschoten I, Janssen-Heijnen ML et al (2006) Pathology practice patterns affect lymph node evaluation and outcome of colon cancer: a population-based study. Ann Oncol 17:1803–1809

    Article  CAS  PubMed  Google Scholar 

  45. Feinstein AR, Sosin DM, Wells CK (1985) The Will Rogers phenomenon: stage migration and new diagnostic techniques as a source of misleading statistics for survival in cancer. N Engl J Med 312:1604–1608

    CAS  PubMed  Google Scholar 

  46. Tsikitis VL, Larson DL, Wolff BG et al (2009) Survival in stage III colon cancer is independent of the total number of lymph nodes retrieved. J Am Coll Surg 208:42–47

    Article  PubMed  Google Scholar 

Download references

Acknowledgment

This study was funded in part from a grant from the Stavanger Health Trust Research Council.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kjetil Søreide.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Søreide, K., Nedrebø, B.S., Søreide, J.A. et al. Lymph Node Harvest in Colon Cancer: Influence of Microsatellite Instability and Proximal Tumor Location. World J Surg 33, 2695–2703 (2009). https://doi.org/10.1007/s00268-009-0255-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00268-009-0255-4

Keywords

Navigation