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Should Lymph Node Micrometastasis be Considered in Node Staging For Gastric Cancer?

The Significance of Lymph Node Micrometastasis in Gastric Cancer

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

Abstract

Background

In TNM staging system, lymph node staging is based on the number of metastatic lymph nodes in gastric cancer and micrometastasis is not considered. Several reports proposed the importance of lymph node micrometastasis as the causative factor for recurrence and poor survival, but it remains controversial among researchers.

Methods

A total of 482 gastric cancer patients who underwent curative resection from 2004 to 2010 at Korea University Medical Center Ansan Hospital, South Korea were prospectively enrolled. For detecting lymph node micrometastasis, immunohistochemical staining with anti-cytokeratin antibody (CAM 5.2) was performed on negative lymph nodes by hematoxylin-eosin (H–E) staining. Survival differences were compared between conventional node staging and new node staging that took micrometastasis into consideration. Also, the prognostic value of lymph node micrometastasis was investigated in multivariate analysis.

Results

A total of 156 patients (32.4 %) showed lymph node micrometastasis. Overall, the micrometastatic group had more advanced tumor and lymph node stage, lymphovascular cancer cell invasion, a higher rate of recurrence, and poor survival. Furthermore, when the cumulative numbers of macro- and micrometastatic lymph nodes were calculated together, the discriminative power of survival difference between each node stage became more stratified. Also, multivariate analysis using Cox’s proportional hazards model demonstrated perineural invasion, pathologic T stage, dissected lymph nodes, macro- and micrometastatic lymph nodes are independent prognostic factors.

Conclusions

Lymph node micrometastasis was clinically significant as a risk factor for recurrent gastric cancer. Lymph node micrometastasis should be considered when estimating TNM stage for determining prognosis and the best treatment strategy.

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References

  1. Siewert JR, Bottcher K, Stein HJ, Roder JD. Relevant prognostic factors in gastric cancer: ten-year results of the German Gastric Cancer Study. Ann Surg. 1998;228(4):449–61.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Nitti D, Marchet A, Olivieri M, et al. Ratio between metastatic and examined lymph nodes is an independent prognostic factor after D2 resection for gastric cancer: analysis of a large European monoinstitutional experience. Ann Surg Oncol. 2003;10(9):1077–85.

    Article  PubMed  Google Scholar 

  3. Kwon SJ, Kim GS. Prognostic significance of lymph node metastasis in advanced carcinoma of the stomach. Br J Surg. 1996;83(11):1600–3.

    Article  CAS  PubMed  Google Scholar 

  4. Maehara Y, Okuyama T, Moriguchi S, et al. Prophylactic lymph node dissection in patients with advanced gastric cancer promotes increased survival time. Cancer. 1992;70(2):392–5.

    Article  CAS  PubMed  Google Scholar 

  5. Sobin LH, Gospodarowicz MK, Wittekind C, International Union against Cancer. TNM classification of malignant tumours. 7th edn. Chichester; Hoboken: Wiley-Blackwell; 2010.

  6. Maehara Y, Oshiro T, Endo K, et al. Clinical significance of occult micrometastasis lymph nodes from patients with early gastric cancer who died of recurrence. Surgery. 1996;119(4):397–402.

    Article  CAS  PubMed  Google Scholar 

  7. Siewert JR, Kestlmeier R, Busch R, et al. Benefits of D2 lymph node dissection for patients with gastric cancer and pN0 and pN1 lymph node metastases. Br J Surg. 1996;83(8):1144–7.

    Article  CAS  PubMed  Google Scholar 

  8. Ishida K, Katsuyama T, Sugiyama A, Kawasaki S. Immunohistochemical evaluation of lymph node micrometastases from gastric carcinomas. Cancer. 1997;79(6):1069–76.

    Article  CAS  PubMed  Google Scholar 

  9. Yonemura Y, Endo Y, Hayashi I, Kawamura T, Yun HY, Bandou E. Proliferative activity of micrometastases in the lymph nodes of patients with gastric cancer. Br J Surg. 2007;94(6):731–6.

    Article  CAS  PubMed  Google Scholar 

  10. Harrison LE, Choe JK, Goldstein M, Meridian A, Kim SH, Clarke K. Prognostic significance of immunohistochemical micrometastases in node negative gastric cancer patients. J Surg Oncol. 2000;73(3):153–7.

    Article  CAS  PubMed  Google Scholar 

  11. Lee HS, Kim MA, Yang HK, Lee BL, Kim WH. Prognostic implication of isolated tumor cells and micrometastases in regional lymph nodes of gastric cancer. World J Gastroenterol. 2005;11(38):5920–5.

    PubMed  Google Scholar 

  12. Lee E, Chae Y, Kim I, Choi J, Yeom B, Leong AS. Prognostic relevance of immunohistochemically detected lymph node micrometastasis in patients with gastric carcinoma. Cancer. 2002;94(11):2867–73.

    Article  PubMed  Google Scholar 

  13. Kim JH, Park JM, Jung CW, et al. The significances of lymph node micrometastasis and its correlation with E-cadherin expression in pT1-T3N0 gastric adenocarcinoma. J Surg Oncol. 2008;97(2):125–30.

    Article  PubMed  Google Scholar 

  14. Cai J, Ikeguchi M, Maeta M, Kaibara N, Sakatani T. Clinicopathological value of immunohistochemical detection of occult involvement in pT3N0 gastric cancer. Gastric Cancer. 1999;2(2):95–100.

    Article  PubMed  Google Scholar 

  15. Cai J, Ikeguchi M, Tsujitani S, Maeta M, Liu J, Kaibara N. Significant correlation between micrometastasis in the lymph nodes and reduced expression of E-cadherin in early gastric cancer. Gastric Cancer. 2001;4(2):66–74.

    Article  CAS  PubMed  Google Scholar 

  16. Yasuda K, Adachi Y, Shiraishi N, Inomata M, Takeuchi H, Kitano S. Prognostic effect of lymph node micrometastasis in patients with histologically node-negative gastric cancer. Ann Surg Oncol. 2002;9(8):771–4.

    Article  PubMed  Google Scholar 

  17. Japanese Gastric Cancer Association. Japanese classification of gastric carcinoma: 3rd English edition. Gastric Cancer. 2011;14(2):101–12.

    Article  Google Scholar 

  18. Japanese Gastric Cancer Association. Japanese gastric cancer treatment guidelines 2010 (ver. 3). Gastric Cancer. 2011;14(2):113–23.

    Article  Google Scholar 

  19. Choi HJ, Kim YK, Kim YH, Kim SS, Hong SH. Occurrence and prognostic implications of micrometastases in lymph nodes from patients with submucosal gastric carcinoma. Ann Surg Oncol. 2002;9(1):13–9.

    Article  PubMed  Google Scholar 

  20. Fukagawa T, Sasako M, Mann GB, et al. Immunohistochemically detected micrometastases of the lymph nodes in patients with gastric carcinoma. Cancer. 2001;92(4):753–60.

    Article  CAS  PubMed  Google Scholar 

  21. Morgagni P, Saragoni L, Scarpi E, et al. Lymph node micrometastases in early gastric cancer and their impact on prognosis. World J Surg. 2003;27(5):558–61.

    Article  PubMed  Google Scholar 

  22. Makin CA, Bobrow LG, Bodmer WF. Monoclonal antibody to cytokeratin for use in routine histopathology. J Clin Pathol. 1984;37(9):975–83.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Hata M, Machi J, Mamou J, et al. Entire-volume serial histological examination for detection of micrometastases in lymph nodes of colorectal cancers. Pathol Oncol Res. 2011;17(4):835–41.

    Article  PubMed Central  PubMed  Google Scholar 

  24. Fukagawa T, Sasako M, Shimoda T, et al. The prognostic impact of isolated tumor cells in lymph nodes of T2N0 gastric cancer: comparison of American and Japanese gastric cancer patients. Ann Surg Oncol. 2009;16(3):609–13.

    Article  CAS  PubMed  Google Scholar 

  25. Fukagawa T, Sasako M, Ito S, et al. The prognostic significance of isolated tumor cells in the lymph nodes of gastric cancer patients. Gastric Cancer. 2010;13(3):191–6.

    Article  PubMed  Google Scholar 

  26. Washington K. 7th edition of the AJCC cancer staging manual: stomach. Ann Surg Oncol. 2010;17(12):3077–9.

    Article  PubMed  Google Scholar 

  27. Peeters KC, Kattan MW, Hartgrink HH, et al. Validation of a nomogram for predicting disease-specific survival after an R0 resection for gastric carcinoma. Cancer. 2005;103(4):702–7.

    Article  PubMed  Google Scholar 

  28. Kattan MW, Karpeh MS, Mazumdar M, Brennan MF. Postoperative nomogram for disease-specific survival after an R0 resection for gastric carcinoma. J Clin Oncol. 2003;21(19):3647–50.

    Article  PubMed  Google Scholar 

  29. Nakajo A, Natsugoe S, Ishigami S, et al. Detection and prediction of micrometastasis in the lymph nodes of patients with pN0 gastric cancer. Ann Surg Oncol. 2001;8(2):158–62.

    Article  CAS  PubMed  Google Scholar 

  30. Ueno S, Tanabe G, Sako K, et al. Discrimination value of the new western prognostic system (CLIP score) for hepatocellular carcinoma in 662 Japanese patients. Cancer of the Liver Italian Program. Hepatology. 2001;34(3):529–34.

    Article  CAS  PubMed  Google Scholar 

  31. Jee YS, Hwang SH, Rao J, et al. Safety of extended endoscopic mucosal resection and endoscopic submucosal dissection following the Japanese Gastric Cancer Association treatment guidelines. Br J Surg. 2009;96(10):1157–61.

    Article  CAS  PubMed  Google Scholar 

  32. Cai J, Ikeguchi M, Maeta M, Kaibara N. Micrometastasis in lymph nodes and microinvasion of the muscularis propria in primary lesions of submucosal gastric cancer. Surgery. 2000;127(1):32–9.

    Article  CAS  PubMed  Google Scholar 

  33. Cai J, Ikeguchi M, Tsujitani S, Maeta M, Kaibara N. Micrometastasis in lymph nodes of mucosal gastric cancer. Gastric Cancer. 2000;3(2):91–6.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Gastroenterologic Surgery, Korea University Medical Center, Seoul, South Korea

    Chang Min Lee MD, Jun-Min Cho MD, You-Jin Jang MD, Sung-Soo Park MD, Seong-Heum Park MD, Seung-Joo Kim MD, Young-Jae Mok MD, Chong-Suk Kim MD & Jong-Han Kim MD

  2. Department of Surgery, Korea University College of Medicine, Seoul, South Korea

    You-Jin Jang MD, Sung-Soo Park MD, Seong-Heum Park MD, Seung-Joo Kim MD, Young-Jae Mok MD, Chong-Suk Kim MD & Jong-Han Kim MD

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  1. Chang Min Lee MD
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Correspondence to Jong-Han Kim MD.

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Lee, C.M., Cho, JM., Jang, YJ. et al. Should Lymph Node Micrometastasis be Considered in Node Staging For Gastric Cancer?. Ann Surg Oncol 22, 765–771 (2015). https://doi.org/10.1245/s10434-014-4073-z

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  • DOI: https://doi.org/10.1245/s10434-014-4073-z

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