Lymph Node and Bone Marrow Micro-Metastasis in Patients with Esophageal Cancer

Articles in Press

Document Type : Review Article

Authors

1 Lung Diseases Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

2 Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

3 Department of Clinical Nutrition, School of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

4 International UNESCO center for Health Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran

5 Brighton & Sussex Medical School, Division of Medical Education, Falmer, Brighton, Sussex BN1 9PH, UK

6 International UNESCO center for Health-Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran

10.22038/jctm.2024.82376.1471

Abstract

Esophageal cancer (EC) is the sixth most common cause of cancer-related mortality globally, due to the high frequency of early metastatic disease. In the past, the presence of metastasis was examined based on histological analysis using hematoxylin and eosin (HE) staining. A high percentage of patients experience recurrence after metastasectomy. Recurrence could be due to the presence of micro-metastasis (MM), which could be detected at sites such as lymph nodes or bone marrow using RT-PCR or immune-histochemical staining. Previous studies have reported inconsistent results with respect to the clinical significance of MM, its impact on survival, and how it is affected by chemotherapy. In this study, we reviewed the (1) clinical significance of MM, (2) methods of detection, (3) sites of occurrence, (4) the mechanism associated with MM, and (5) the role of chemotherapy and radiotherapy in patients with EC.

Keywords

References

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians. 2018 Nov;68(6):394-424..
  2. Fatehi Hassanabad A, Chehade R, Breadner D, Raphael J. Esophageal carcinoma: towards targeted therapies. Cellular Oncology. 2020 Apr;43:195-209.
  3. Noone AM, Howlader N, Krapcho MA, Miller D, Brest A, Yu M, et al. SEER Cancer Statistics Review, 1975-2015, National Cancer Institute. Bethesda, MD [Internet]. 2018 Apr 16
  4. Kamangar F, Malekzadeh R, Dawsey SM, Saeidi F. Esophageal cancer in Northeastern Iran: a review. 2007.
  5. Chen SB, Liu DT, Huang SJ, Weng HR, Wang G, Li H, et al. Prognostic value of occult lymph node metastases in patients with completely resected esophageal squamous cell carcinoma. Scientific Reports. 2020 Dec 15;10(1):22007.
  6. Rice TW, Ishwaran H, Ferguson MK, Blackstone EH, Goldstraw P. Cancer of the esophagus and esophagogastric junction: an eighth edition staging primer. Journal of Thoracic Oncology. 2017 Jan 1;12(1):36-42.
  7.  Marjanovic G, Schricker M, Walch A, Zur Hausen A, Hopt UT, Imdahl A, et al. Detection of lymph node involvement by cytokeratin immunohistochemistry is an independent prognostic factor after curative resection of esophageal cancer. Journal of Gastrointestinal Surgery. 2011 Jan 1;15(1):29-37.
  8. Sobin LH, Gospodarowicz MK, Wittekind C, editors. TNM classification of malignant tumours. John Wiley & Sons; 2011 Aug 31..
  9.  Xu X, Zheng G, Zhang T, Zhao Y, Zheng Z. Clinical significance of metastasis or micrometastasis to the lymph node along the superior mesenteric vein in gastric carcinoma: a retrospective analysis. Frontiers in Oncology. 2021 Jul 29;11:707249.
  10. De Boer M, Van Deurzen CH, Van Dijck JA, Borm GF, Van Diest PJ, Adang EM, et al. Micrometastases or isolated tumor cells and the outcome of breast cancer. New England Journal of Medicine. 2009 Aug 13;361(7):653-63.
  11. Wang Z, Liu XY, Liu FY, Chen JH. Lymph node occult micrometastasis in patients with non-small cell lung carcinoma: genetic diagnosis and its impact on prognosis. Ai Zheng= Aizheng= Chinese Journal of Cancer. 2003 Nov 1;22(11):1204-8.
  12. Sun ZG, Wang Z, Liu XY, Liu FY. Mucin 1 and vascular endothelial growth factor C expression correlates with lymph node metastatic recurrence in patients with N0 esophageal cancer after Ivor‐Lewis esophagectomy. World journal of surgery. 2011 Jan;35(1):70-7.
  13. Tanabe T, Nishimaki T, Watanabe H, Ajioka Y, Akazawa K, Komukai S, et al. Immunohistochemically detected micrometastasis in lymph nodes from superficial esophageal squamous cell carcinoma. Journal of surgical oncology. 2003 Mar;82(3):153-9.
  14. Jiao X, Krasna MJ. Clinical significance of micrometastasis in lung and esophageal cancer: a new paradigm in thoracic oncology. The Annals of thoracic surgery. 2002 Jul 1;74(1):278-84.
  15. Dearnaley DP, Sloane JP, Ormerod MG, Steele K, Coombes RC, Clink HM, et al. Increased detection of mammary carcinoma cells in marrow smears using antisera to epithelial membrane antigen. British Journal of Cancer. 1981 Jul;44(1):85-90.
  16. Racila E, Euhus D, Weiss AJ, Rao C, McConnell J, Terstappen LW, et al. Detection and characterization of carcinoma cells in the blood. Proceedings of the National Academy of Sciences. 1998 Apr 14;95(8):4589-94.
  17. Naume B, Borgen E, Beiske K, HERSTAD TK, Ravnås G, Renolen A, et al. Immunomagnetic techniques for the enrichment and detection of isolated breast carcinoma cells in bone marrow and peripheral blood. Journal of hematotherapy. 1997 Apr;6(2):103-14.
  18. Hata M, Machi J, Mamou J, Yanagihara ET, Saegusa-Beecroft E, Kobayashi GK, et al. Entire-volume serial histological examination for detection of micrometastases in lymph nodes of colorectal cancers. Pathology & Oncology Research. 2011 Dec;17:835-41.
  19. Bagheri R, Maddah G, Saedi HS, Sadeghian MH, Roodbari S. Bone marrow involvement in esophageal cancer patients who underwent surgical resection. European journal of cardio-thoracic surgery. 2011 Aug 1;40(2):343-6.
  20. Yoshioka S, Fujiwara Y, Sugita Y, Okada Y, Yano M, Tamura S, et al. Real-time rapid reverse transcriptase—polymerase chain reaction for intraoperative diagnosis of lymph node micrometastasis: Clinical application for cervical lymph node dissection in esophageal cancers. Surgery. 2002 Jul 1;132(1):34-40.
  21. von Knebel Doeberitz M, Lacroix J. Nucleic acid based techniques for the detection of rare cancer cells in clinical samples. Cancer and Metastasis Reviews. 1999 Mar;18:43-64.
  22. Dorudi S, Kinrade E, Marshall NC, Feakins R, Williams NS, Bustin SA. Genetic detection of lymph node micrometastases in patients with colorectal cancer. Journal of British Surgery. 1998 Jan;85(1):98-100.
  23. Iddings D, Ahmad A, Elashoff D, Bilchik A. The prognostic effect of micrometastases in previously staged lymph node negative (N0) colorectal carcinoma: a meta-analysis. Annals of surgical oncology. 2006 Nov;13:1386-92.
  24. Salmon SE, Hamburger AW, Soehnlen B, Durie BG, Alberts DS, Moon TE. Quantitation of differential sensitivity of human-tumor stem cells to anticancer drugs. New England Journal of Medicine. 1978 Jun 15;298(24):1321-7.
  25. Ryan P, McCarthy S, Kelly J, Collins JK, Dunne C, Grogan L, et al. Prevalence of bone marrow micrometastases in esophagogastric cancer patients with and without neoadjuvant chemoradiotherapy. Journal of Surgical Research. 2004 Mar 1;117(1):121-6.
  26. Gerges N, Jabado N. Biomarkers in cancer micrometastasis: where are we at?. Bioanalysis. 2010 May 1;2(5):881-99.
  27. Chambers AF, Naumov GN, Vantyghem SA, Tuck AB. Molecular biology of breast cancer metastasis Clinical implications of experimental studies on metastatic inefficiency. Breast Cancer Research. 2000 Dec;2:1-8.
  28. Cameron MD, Schmidt EE, Kerkvliet N, Nadkarni KV, Morris VL, Groom AC, et al. Temporal progression of metastasis in lung: cell survival, dormancy, and location dependence of metastatic inefficiency. Cancer research. 2000 May 1;60(9):2541-6.
  29. Naumov GN, MacDonald IC, Weinmeister PM, Kerkvliet N, Nadkarni KV, Wilson SM, et al. Persistence of solitary mammary carcinoma cells in a secondary site: a possible contributor to dormancy. Cancer research. 2002 Apr 1;62(7):2162-8.
  30. Chaffer CL, Weinberg RA. A perspective on cancer cell metastasis. science. 2011 Mar 25;331(6024):1559-64.
  31. Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. nature. 2001 Nov 1;414(6859):105-11.
  32.  Maugeri-Saccà M, Vigneri P, De Maria R. Cancer stem cells and chemosensitivity. Clinical Cancer Research. 2011 Aug 1;17(15):4942-7.
  33. Javid H, Hashemy SI, Heidari MF, Esparham A, Gorgani-Firuzjaee S. The Anticancer Role of Cerium Oxide Nanoparticles by Inducing Antioxidant Activity in Esophageal Cancer and Cancer Stem‐Like ESCC Spheres. BioMed Research International. 2022;2022(1):3268197.
  34. Javid H, Afshari AR, Zahedi Avval F, Asadi J, Hashemy SI. Aprepitant promotes caspase‐dependent apoptotic cell death and G2/M arrest through PI3K/Akt/NF‐κB axis in cancer stem‐like esophageal squamous cell carcinoma spheres. BioMed Research International. 2021;2021(1):8808214.
  35. Robey-Cafferty SS, El-Naggar AK, Sahin AA, Bruner JM, Ro JY, Cleary KR. Prognostic factors in esophageal squamous carcinoma: a study of histologic features, blood group expression, and DNA ploidy. American journal of clinical pathology. 1991 Jun 1;95(6):844-9.
  36. Sgourakis G, Gockel I, Lyros O, Hansen T, Mildenberger P, Lang H. Detection of lymph node metastases in esophageal cancer. Expert review of anticancer therapy. 2011 Apr 1;11(4):601-12.
  37. Begg CB, Cramer LD, Hoskins WJ, Brennan MF. Impact of hospital volume on operative mortality for major cancer surgery. Jama. 1998 Nov 25;280(20):1747-51.
  38. Hagihara T, Uenosono Y, Arigami T, Kozono T, Arima H, Yanagita S, et al. Assessment of sentinel node concept in esophageal cancer based on lymph node micrometastasis. Annals of surgical oncology. 2013 Sep;20:3031-7.
  39. Uenosono Y, Arigami T, Yanagita S, Kozono T, Arima H, Hirata M, et al. Sentinel node navigation surgery is acceptable for clinical T1 and N0 esophageal cancer. Annals of surgical oncology. 2011 Jul;18:2003-9.
  40. Noura S, Yamamoto H, Miyake Y, Kim BN, Takayama O, Seshimo I, et al. Immunohistochemical assessment of localization and frequency of micrometastases in lymph nodes of colorectal cancer. Clinical cancer research. 2002 Mar 1;8(3):759-67.
  41. Shiozaki H, Fujiwara Y, Hirai T, Matsubara H, Mori M, Nakamura T, et al. Clinical significance of immunohistochemically detected lymph node micrometastasis in patients with histologically node-negative esophageal carcinoma: a multi-institutional study. Esophagus. 2007 Mar;4:35-9.
  42. Schlimok G, Riethmüller G. Detection, characterization and tumorigenicity of disseminated tumor cells in human bone marrow. InSeminars in Cancer Biology 1990 Jun 1 (Vol. 1, No. 3, pp. 207-215).
  43. Spence GM, Graham AN, Mulholland K, Maxwell P, McCluggage WG, Sloan JM, et al. Bone marrow micrometastases and markers of angiogenesis in esophageal cancer. The Annals of thoracic surgery. 2004 Dec 1;78(6):1944-9.
  44. O'Sullivan GC, Sheehan D, Clarke A, Stuart R, Kelly J, Kiely MD, et al. Micrometastases in esophagogastric cancer: high detection rate in resected rib segments. Gastroenterology. 1999 Mar 1;116(3):543-8.
  45. Domschke C, Diel IJ, Englert S, Kalteisen S, Mayer L, Rom J, et al. Prognostic value of disseminated tumor cells in the bone marrow of patients with operable primary breast cancer: a long-term follow-up study. Annals of surgical oncology. 2013 Jun;20:1865-71.
  46. Wang G, Wang S, Li Y, Yu Y, Song Z, Zhao Q, et al. Clinical study of disseminated tumor cells in bone marrow of patients with gastric cancer. Hepato-gastroenterology. 2013 Mar 1;60(122):273-6.
  47. Karstens KF, Ghadban T, Effenberger K, Sauter G, Pantel K, Izbicki JR, et al. Lymph node and bone marrow micrometastases define the prognosis of patients with pN0 esophageal cancer. Cancers. 2020 Mar 4;12(3):588.
  48. Pantel K, Alix-Panabières C. Bone marrow as a reservoir for disseminated tumor cells: a special source for liquid biopsy in cancer patients. BoneKEy reports. 2014;3.
  49. Yang F, Li Z, Shao JB, Gao W, Sun ZG. Mucin 1 expression correlation with lymph node metastasis and micrometastasis and poor prognosis in patients with esophageal squamous cell carcinomas. Archives of Medical Science: AMS. 2019 Oct 28;19(3):638.
  50. Heeren PA, Kelder W, Blondeel I, Van Westreenen HL, Hollema H, Plukker JT. Prognostic value of nodal micrometastases in patients with cancer of the gastro-oesophageal junction. European Journal of Surgical Oncology (EJSO). 2005 Apr 1;31(3):270-6.
  51. Li SH, Wang Z, Liu XY, Liu FY, Sun ZY, Xue H. Lymph node micrometastasis: a predictor of early tumor relapse after complete resection of histologically node-negative esophageal cancer. Surgery today. 2007 Dec;37:1047-52.
  52. Komukai S, Nishimaki T, Watanabe H, Ajioka Y, Suzuki T, Hatakeyama K. Significance of immunohistochemically demonstrated micrometastases to lymph nodes in esophageal cancer with histologically negative nodes. Surgery. 2000 Jan 1;127(1):40-6.
  53. Doki Y, Ishikawa O, Mano M, Hiratsuka M, Sasaki Y, Kameyama M, et al. Cytokeratin deposits in lymph nodes show distinct clinical significance from lymph node micrometastasis in human esophageal cancers. Journal of Surgical Research. 2002 Sep 1;107(1):75-81.
  54. Gray RT, O'donnell ME, Verghis RM, McCluggage WG, Maxwell P, McGuigan JA, et al. Bone marrow micrometastases in esophageal carcinoma: a 10-year follow-up study. Diseases of the Esophagus. 2012 Dec 1;25(8):709-15.
  55. Prenzel KL, Hölscher AH, Drebber U, Agavonova M, Gutschow CA, Bollschweiler E. Prognostic impact of nodal micrometastasis in early esophageal cancer. European Journal of Surgical Oncology (EJSO). 2012 Apr 1;38(4):314-8.
  56. Glickman JN, Torres C, Wang HH, Turner JR, Shahsafaei A, Richards WG, et al. The prognostic significance of lymph node micrometastasis in patients with esophageal carcinoma. Cancer: Interdisciplinary International Journal of the American Cancer Society. 1999 Feb 15;85(4):769-78.
  57. Waterman TA, Hagen JA, Peters JH, DeMeester SR, Taylor CR, DeMeester TR. The prognostic importance of immunohistochemically detected node metastases in resected esophageal adenocarcinoma. The Annals of thoracic surgery. 2004 Oct 1;78(4):1161-9.
  58. Nakamura T, Ide H, Eguchi R, Hayashi K, Ota M, Takasaki K. Clinical implications of lymph node micrometastasis in patients with histologically node‐negative (pN0) esophageal carcinoma. Journal of surgical oncology. 2002 Apr;79(4):224-9.
  59. Sato F, Shimada Y, Li Z, Watanabe G, Maeda M, Imamura M. Lymph node micrometastasis and prognosis in patients with oesophageal squamous cell carcinoma. British journal of surgery. 2001 Mar;88(3):426-32.
  60. Hosch S, Kraus J, Scheunemann P, Izbicki JR, Schneider C, Schumacher U, et al. Malignant potential and cytogenetic characteristics of occult disseminated tumor cells in esophageal cancer. Cancer research. 2000 Dec 15;60(24):6836-40.
  61. Griniatsos J, Michail O, Dimitriou N, Karavokyros I. Lymph node, peritoneal and bone marrow micrometastases in gastric cancer: Their clinical significance. World Journal of Gastrointestinal Oncology. 2012 Feb 2;4(2):16.
  62. Zhang X, Chen SB, Chen JX, Wen J, Yang H, Xie MR, et al. CK19 mRNA expression in the bone marrow of patients with esophageal squamous cell carcinoma and its clinical significance. Diseases of the Esophagus. 2010 Jul 1;23(5):437-43.
  63. Ryan P, Furlong H, Murphy CG, O'Sullivan F, Walsh TN, Shanahan F, et al. Prognostic significance of prospectively detected bone marrow micrometastases in esophagogastric cancer: 10‐year follow‐up confirms prognostic significance. Cancer Medicine. 2015 Aug;4(8):1281-8.
  64. Konczalla L, Ghadban T, Effenberger KE, Wöstemeier A, Riethdorf S, Uzunoglu FG, et al. Prospective comparison of the prognostic relevance of circulating tumor cells in blood and disseminated tumor cells in bone marrow of a single patient's cohort with esophageal cancer. Annals of surgery. 2021 Feb 1;273(2):299-305.
  65. Chen SB, Su XD, Ma GW, Lin P, Wen J, Wang FX, et al. Prognostic value of bone marrow micrometastasis in patients with operable esophageal squamous cell carcinoma: A long-term follow-up study. Journal of Thoracic Oncology. 2014 Aug 1;9(8):1207-13.
  66. Nakamura T, Matsunami K, Hayashi K, Ota M, Ide H, Takasaki K. Detection of bone marrow micrometastasis in esophageal cancer patients by immunomagnetic separation. Oncology reports. 2004 May 1;11(5):999-1003.
  67. Natsugoe S, Nakashima S, Nakajo A, Matsumoto M, Okumura H, Tokuda K, et al. Bone marrow micrometastasis detected by RT-PCR in esophageal squamous cell carcinoma. Oncology reports. 2003 Nov 1;10(6):1879-83.
  68. van Hagen P, Hulshof MC, Van Lanschot JJ, Steyerberg EW, Henegouwen MV, Wijnhoven BP, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. New England Journal of Medicine. 2012 May 31;366(22):2074-84.
  69. Yanagi M, Sasaki K, Uchikado Y, Omoto I, Arigami T, Kurahara H, et al. Effect of neoadjuvant chemoradiotherapy on lymph node micrometastases in thoracic esophageal cancer. Anticancer Research. 2018 Feb 1;38(2):893-900.
  70. Natsugoe S, Matsumoto M, Nakashima S, Okumura H, Miyazono F, Kijima F, et al. Effect of neoadjuvant chemotherapy for lymph node micrometastasis and tumor cell microinvolvement in the patients with esophageal carcinoma. Cancer letters. 2000 Oct 31;159(2):119-25.
  71. Hiraki Y, Kimura Y, Imano M, Kato H, Iwama M, Shiraishi O, et al. Controlling lymph node micrometastases by neoadjuvant chemotherapy affects the prognosis in advanced esophageal squamous cell carcinoma. Surgery Today. 2021 Jan;51:118-26.
  72. Wang D, Smit JK, Zwaan E, Muijs CT, Groen H, Hollema H, et al. Neoadjuvant therapy reduces the incidence of nodal micrometastases in esophageal adenocarcinoma. The American Journal of Surgery. 2013 Nov 1;206(5):732-8.
  73. Matsuyama J, Doki Y, Yasuda T, Miyata H, Fujiwara Y, Takiguchi S, et al. The effect of neoadjuvant chemotherapy on lymph node micrometastases in squamous cell carcinomas of the thoracic esophagus. Surgery. 2007 May 1;141(5):570-80.
  74. Matsumoto M, Natsugoe S, Nakashima S, Sakamoto F, Okumura H, Sakita H, et al. Clinical significance of lymph node micrometastasis of pN0 esophageal squamous cell carcinoma. Cancer letters. 2000 May 29;153(1-2):189-97.
  75. Macadam R, Sarela A, Wilson J, MacLennan K, Guillou P. Bone marrow micrometastases predict early post-operative recurrence following surgical resection of oesophageal and gastric carcinoma. European Journal of Surgical Oncology (EJSO). 2003 Jun 1;29(5):450-4.
  76. Thorban S, Rosenberg R, Busch R, Roder RJ. Epithelial cells in bone marrow of oesophageal cancer patients: a significant prognostic factor in multivariate analysis. British journal of cancer. 2000 Jul;83(1):35-9.
Journal of Cardio-Thoracic Medicine

Articles in Press, Accepted Manuscript
Available Online from 01 October 2024

Files

Share

How to cite

Statistics