Skip to main content

Advertisement

Log in

Significance of isolated tumor cells in lymph nodes among gastric cancer patients

  • Original Paper
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

To determine the frequency and prognostic impact of isolated tumor cells (ITC) in regional lymph nodes judged to be tumor free in conventional histopathology among gastric cancer patients.

Methods

Among 161 patients who underwent gastrectomy and D2-lymphadenectomy, 56 were staged pN0 (35%). Archival paraffin blocks of 1148 resected regional lymph nodes of those pN0 patients were reevaluated for ITC using monoclonal antibody Ber-EP4. Patients with and without ITC were compared with regard to the distribution of various clinicopathological factors. Prognostic impact of ITC was tested in uni- and multivariate analysis.

Results

Of 56 pN0 patients, 33 (59%) exhibited single Ber-Ep4 immunoreactive cells or small cell clusters in at least one lymph node. The occurrence of ITC was not dependent on other clinicopathological factors. ITC impaired patients’ prognoses significantly in uni- as well as multivariate analyses [estimated 5-year survival rate: 82% for pN0(i−) vs 58% for pN0(i+) (p=0.059) and 15% for pN1/2 (p=0.0005 and p<0.0001, respectively)].

Conclusion

ITC are a frequent event in apparently tumor-free lymph nodes of gastric cancer patients and are overlooked by conventional histopathology. They are encountered even in limited stages of disease and impair patients’ prognoses. This should be borne in mind when advocating local resection for early gastric 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

  • Adell G, Boeryd B, Franlund B, Sjördahl R, Hakansson L (1996) Occurrence and prognostic importance of micrometastases in regional lymph nodes in Dukes’ B colorectal carcinoma: an immunohistochemical study. Eur J Cancer 162:637–642

    CAS  Google Scholar 

  • Broll R, Schauer V, Schimmelpenning H, Strik M, Woltmann A, Best R, Bruch HP, Duchrow M (1997) Prognostic relevance of occult tumor cells in lymph nodes of colorectal carcinomas: an immunohistochemical study. Dis Colon Rectum 40:1465–1471

    CAS  PubMed  Google Scholar 

  • Cai J, Ikeguchi M, Maeta M, Kaibara N (2000) Micrometastasis in lymph nodes and microinvasion of the muscularis propria in primary lesions of submucosal gastric cancer. Surgery 127:32–39

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Dobashi K, Sugio K, Osaki T, Oka T, Yasumoto K (1997) Micrometastatic p53-positive cells in the lymph nodes of non-small cell lung cancer: prognostic relevance. J Thorac Cardiovasc Surg 114:339–346

    CAS  PubMed  Google Scholar 

  • Domagala W, Bedner E, Chosia M (1991) Keratin-positive reticulum cells in fine needle aspirates and touch imprints of hyperplastic lymph nodes. Acta Cytol 36:241–251

    Google Scholar 

  • Fukagawa T, Sasako M, Mann GB, Sano T, Katai H, Maruyama K, Nakanishi Y, Shimoda T (2001) Immunohistochemically detected micrometastases of the lymph nodes in patients with gastric carcinoma. Cancer 92:753–760

    Article  CAS  PubMed  Google Scholar 

  • Gu CD, Osaki T, Oyama T, Inoue M, Kodate M, Dobashi K, Oka T, Yasumoto K (2002) Detection of micrometastatic tumor cells in pN0 lymph nodes of patients with completely resected nonsmall cell lung cancer. Ann Surg 235:133–139

    Article  PubMed  Google Scholar 

  • Harrison LE, Choe JK, Goldstein M, Meridian A, Kim SH, Clarke K (2000) Prognostic significance of immunohistochemical micrometastases in node negative gastric cancer patients. J Surg Oncol 73:153–157

    Article  CAS  PubMed  Google Scholar 

  • Heiss MM, Algayer H, Grützner KU, Babic R, Jauch KW, Schildberg FW (1997) Clinical value of extended biologic staging by bone marrow micrometastases and tumor-associated proteases in gastric cancer. Ann Surg 226:736–744

    Article  CAS  PubMed  Google Scholar 

  • Hermanek P, Hutter P, Sobin L, Wittekind K (1999) Classification of isolated tumor cells and micrometastasis. Cancer 86:2668–2674

    Article  CAS  PubMed  Google Scholar 

  • Higashi H, Natsugoe S, Ishigami S, Uenosono Y, Matsumoto M, Nakajo A, Miyazono F, Hokita S, Takao S, Aikou T (2003) Distribution of lymph node metastasis including micrometastasis in gastric cancer with submucosal invasion. World J Surg 27:455–459

    Article  PubMed  Google Scholar 

  • Hosch SB, Knoefel WT, Metz S, Stoecklein N, Neindorf A, Broelsch CE, Izbicki J (1997) Early lymphatic tumor cell dissemination in pancreatic cancer: frequency and prognostic significance. Pancreas 15:154–159

    CAS  PubMed  Google Scholar 

  • Inoue S, Nakao A, Kasai Y, Harada A, Nonami T, Takagi H (1995) Detection of hepatic micrometastasis in pancreatic adenocarcinoma patients by two-stage polymerase chain reaction/restriction fragment length polymorphism analysis. Jpn J Cancer Res 86:626–630

    CAS  PubMed  Google Scholar 

  • Ishida K, Katsuyama T, Sugiyama A, Kawasaki S (1997) Immunohistochemical evaluation of lymph node micrometastases from gastric carcinomas. Cancer 79:1069–1076

    Article  CAS  PubMed  Google Scholar 

  • Izbicki JR, Hosch SB, Pichlmeier U, Rehders A, Busch C, Niendorf A, Passlick B, Broelsch CE, Pantel K (1997) Prognostic value of immunohistochemically identifiable tumor cells in lymph nodes of patients with complete resected esophageal cancer. N Engl J Med 337:1188–1194

    Article  CAS  PubMed  Google Scholar 

  • Jung R, Petersen K, Krüger W, Wolf M, Wagener C, Zander A, Neumaier M (1999) Detection of micrometastasis by cytokeratin 29 RT-PCR is limited due to stable background transcription in granulocytes. Br J Cancer 81:870–873

    Article  CAS  PubMed  Google Scholar 

  • Katai H, Maruyama K, Sasako M, Sano T, Okajima K, Kinoshita T (1994) Mode of recurrence after gastric cancer surgery. Digest Surg 11:99–103

    Google Scholar 

  • Kestlmeier R, Busch R, Fellbaum C, Boettcher K, Reich U, Siewert JR, Höfler H (1997) Häufigkeit und prognostische Bedeutung von epitheloidzelligen Reaktionen und Mikrokarzinosen in den regionären Lymphknoten beim Magenkarzinom. Pathologe 18:124–130

    Article  CAS  PubMed  Google Scholar 

  • Kikuchi Y, Tsuchiya A, Ando Y, Yoshida T, Takenosita S (1999) Immunohistochemical detection of lymph node microinvolvement in node-negative gastric cancer. Gastric Cancer 2:173–178

    Article  PubMed  Google Scholar 

  • Latza U, Niedobitek G, Schwarting R, Nekarda H, Stein H (1990) Ber-Ep4: new monoclonal antibody which distinguishes epithelia from mesothelia. J Clin Pathol 43:213–219

    CAS  PubMed  Google Scholar 

  • Lee E, Chae Y, Kim I, Choi J, Yeom B, Leong A (2002) Prognostic relevance of immunohistochemically detected lymph node micrometastasis in patients with gastric carcinoma. Cancer 94:2867–2873

    Article  PubMed  Google Scholar 

  • Maehara Y, Oshiro T, Endo K, Baba H, Oda S, Ichiyoshi Y, Kohnoe S, Sugimachi K (1996) Clinical significance of occult micrometastasis in lymph nodes from patients with early gastric cancer who died of recurrence. Surgery 119:397–402

    CAS  PubMed  Google Scholar 

  • Matsumoto M, Natsugoe S, Ishigami S, Nakashima S, Nakajo A, Miyazono F, Hokita S, Takao S, Eizuru Y, Aikou T (2002) Lymph node micrometastasis and lymphatic mapping determined by reverse transcriptase-polymerase chain reaction in pN0 gastric carcinoma. Surgery 131:630–635

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Moll R, Lowe A, Laufer J, Franke WW (1992) Cytokeratin 20 in human carcinomes: a new diagnostic marker by monoclonal antibodies. Am J Pathol 140:427–447

    CAS  PubMed  Google Scholar 

  • Momburg F, Moldenhauer G, Hämmerling GJ, Möller P (1987) Immunohistochemical study of the expression of a Mr 34,000 human epithelium-specific surface glycoprotein in normal and malignant tissue. Cancer Res 47:2883–2891

    CAS  PubMed  Google Scholar 

  • Morgagni P, Paragoni L, Scarpi E, Zattini PS, Zaccaroni A, Morgagni D, Bazzocchi F (2003) Lymph node micrometastases in early gastric cancer and their impact on prognosis. World J Surg 27:558–561

    Article  PubMed  Google Scholar 

  • Nakajo A, Natsugoe S, Ishigami S, Matsumoto M, Nakashima S, Hokita S, Baba M, Tako S, Aikou T (2001) Detection and prediction of micrometastasis in the lymph nodes of patients with pNO gastric cancer. Ann Surg Oncol 8:158–162

    Article  CAS  PubMed  Google Scholar 

  • Okada Y, Fujiwara Y, Yamamoto H, Sugita Y, Yasuda T, Doki Y, Tamura S, Yano M, Shiozaki H, Matsuura N, Monden M (2001) Genetic detection of lymph node micrometastases in patients with gastric carcinoma by multiple-marker reverse transcriptase-polymerase chain reaction assay. Cancer 92:2056–2064

    Article  CAS  PubMed  Google Scholar 

  • Pantel K, Schlimok G, Angstwurm M, Weckermann D, Schmaus W, Gath H, Passlick B, Izbicki JR, Riethmüller G (1994) Methodological analysis of immunocytochemical screening for disseminated epithelial tumor cells in bone marrow. J Haematother 3:165–173

    CAS  Google Scholar 

  • Pantel K (2001) Micrometastasis. In: Schwab M (ed) Encyclopedic reference of cancer. Springer, Berlin Heidelberg New York, pp 567–571

  • Passlick B, Izbicki JR, Kubuschok B, Nathrath W, Thetter O, Pichelmaier U, Schweiberer L, Riethmüller G, Pantel K (1994) Immunohistochemical assessment of individual tumour cells in lymph nodes of patients with non-small cell lung cancer. J Clin Oncol 12:1827–1832

    CAS  PubMed  Google Scholar 

  • Saragoni L, Gaudio M, Morgagni P, Folli S, Bazzocchi F, Scarpi E, Saragoni A (2000) Identification of occult micrometastases in patients with early gastric cancer using anti-cytokeratin monoclonal antibodies. Oncol Rep 7:535–539

    CAS  PubMed  Google Scholar 

  • Siewert JR, Kestlmeier R, Busch R, Böttcher K, Roder JD, Müller J, Fellbaum C, Höfler H (1996) Benefits of D2 lymph node dissection for patients with gastric cancer and pN0 and pN1 lymph node metastases. Br J Surg 83:1144–1147

    CAS  PubMed  Google Scholar 

  • Stachura J, Zembala M, Heitzman J, Korabiowska M, Schauer A (1998) Lymph node micrometastases in early gastric carcinoma alone inadequately reflect the new model of metastatic development. Pol J Pathol 49:155–157

    CAS  PubMed  Google Scholar 

  • Suzuki H, Miho O, Watanabe Y, Kohyama M, Nago F (1989) Endoscopic laser therapy in the curative and palliative treatment of upper gastrointestinal cancer. World J Surg 13:158–164

    CAS  PubMed  Google Scholar 

  • Traweek ST, Liu J, Battifora H (1993) Keratin gene expression in non-epithelial tissues. Am J Pathol 142:1111–1118

    CAS  PubMed  Google Scholar 

  • UICC / International Union against Cancer (2002) TNM classification of malignant tumors, 6th edn. Wiley-Liss, New York

  • Yasuda K, Adachi Y, Shiraishi N, Inomata M, Takeuchi H, Kitano S (2002) Prognostic effect of lymph node micrometastasis in patients with histologically node-negative gastric cancer. Ann Surg Oncol 9:771–774

    Article  PubMed  Google Scholar 

Download references

Acknowledgement. The authors are grateful to T. Supramaniam and K. Wesselhöft for tissue preparation.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Olaf Horstmann.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Horstmann, O., Füzesi, L., Markus, P.M. et al. Significance of isolated tumor cells in lymph nodes among gastric cancer patients. J Cancer Res Clin Oncol 130, 733–740 (2004). https://doi.org/10.1007/s00432-004-0609-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-004-0609-0

Keywords

Navigation