Skip to main content

Advertisement

SpringerLink
Log in

Molecular markers and staging of early esophageal cancer

  • Current Concepts in Clinical Surgery
  • Published:
Langenbeck's Archives of Surgery Aims and scope Submit manuscript

Abstract

Background

Patients with early esophageal cancer experience varying clinical outcomes despite identical tumor staging by standard diagnostic methods because clinical and histopathological staging fail to reveal the underlying complex biology of cancer.

Methods and focus

This review discusses some of the current concepts of molecular staging with the potential to enhance the current staging methods of patients with early esophageal cancer.

Conclusions

Understanding the molecular biology of esophageal cancer has increased substantially, and clinicians anticipate the translation of the gained knowledge into patient care. Numerous molecular techniques are potentially available for analyzing biological aspects of the individual tumor for improved staging.

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. Lerut T, Coosemans W, Decker G, De Leyn P, Nafteux P, Van Raemdonck D (2001) Cancer of the esophagus and gastro-esophageal junction: potentially curative therapies. Surg Oncol 10:113–122

    Article  CAS  PubMed  Google Scholar 

  2. Hulscher JB, van Sandick JW, de Boer AG, Wijnhoven BP, Tijssen JG, Fockens P, Stalmeier PF, ten Kate FJ, van Dekken H, Obertop H, Tilanus HW, van Lanschot JJ (2002) Extended transthoracic resection compared with limited transhiatal resection for adenocarcinoma of the esophagus. N Engl J Med 347:1662–1669

    Article  PubMed  Google Scholar 

  3. Hagen JA, DeMeester SR, Peters JH, Chandrasoma P, DeMeester TR (2001) Curative resection for esophageal adenocarcinoma: analysis of 100 en bloc esophagectomies. Ann Surg 234:520–530

    Article  CAS  PubMed  Google Scholar 

  4. Ormsby AH, Petras RE, Henricks WH, Rice TW, Rybicki LA, Richter JE, Goldblum JR (2002) Observer variation in the diagnosis of superficial oesophageal adenocarcinoma. Gut 51:671–676

    Article  CAS  PubMed  Google Scholar 

  5. Reid BJ, Haggitt RC, Rubin CE, Roth G, Surawicz CM, Van Belle G, Lewin K, Weinstein WM, Antonioli DA, Goldman H, et al (1988) Observer variation in the diagnosis of dysplasia in Barrett's esophagus. Hum Pathol 19:166–178

    Google Scholar 

  6. Meltzer SJ (1996) The molecular biology of esophageal carcinoma. Recent Results Cancer Res 142:1–8

    CAS  PubMed  Google Scholar 

  7. Blant SA, Ballini JP, Caron CT, Fontolliet C, Monnier P, Laurini NR (2001) Evolution of DNA ploidy during squamous cell carcinogenesis in the esophagus. Dis Esophagus 14:178–184

    Article  CAS  PubMed  Google Scholar 

  8. Galipeau PC, Cowan DS, Sanchez CA, Barrett MT, Emond MJ, Levine DS, Rabinovitch PS, Reid BJ (1996) 17p (p53) allelic losses, 4 N (G2/tetraploid) populations, and progression to aneuploidy in Barrett's esophagus. Proc Natl Acad Sci U S A 93:7081–7084

    Article  CAS  PubMed  Google Scholar 

  9. Reid BJ, Blount PL, Rubin CE, Levine DS, Haggitt RC, Rabinovitch PS (1992) Flow-cytometric and histological progression to malignancy in Barrett's esophagus: prospective endoscopic surveillance of a cohort. Gastroenterology 102:1212–1219

    CAS  PubMed  Google Scholar 

  10. Robaszkiewicz M, Hardy E, Volant A, Nousbaum JB, Cauvin JM, Calament G, Robert FX, Saleun JP, Gouerou H (1991) [Flow cytometric analysis of cellular DNA content in Barrett's esophagus. A study of 66 cases]. Gastroenterol Clin Biol 15:703–710

    CAS  PubMed  Google Scholar 

  11. Teodori L, Gohde W, Persiani M, Ferrario F, Tirindelli Danesi D, Scarpignato C, Di Tondo U, Alo P, Capurso L (1998) DNA/protein flow cytometry as a predictive marker of malignancy in dysplasia-free Barrett's esophagus: thirteen-year follow-up study on a cohort of patients. Cytometry 34:257–263

    Article  CAS  PubMed  Google Scholar 

  12. Reid BJ, Levine DS, Longton G, Blount PL, Rabinovitch PS (2000) Predictors of progression to cancer in Barrett's esophagus: baseline histology and flow cytometry identify low- and high-risk patient subsets. Am J Gastroenterol 95:1669–1676

    Article  CAS  PubMed  Google Scholar 

  13. Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70

    CAS  PubMed  Google Scholar 

  14. Lam AK (2000) Molecular biology of esophageal squamous cell carcinoma. Crit Rev Oncol Hematol 33:71–90

    Article  CAS  PubMed  Google Scholar 

  15. Mandard AM, Hainaut P, Hollstein M (2000) Genetic steps in the development of squamous cell carcinoma of the esophagus. Mutat Res 462:335–342

    Article  CAS  PubMed  Google Scholar 

  16. Jankowski JA, Harrison RF, Perry I, Balkwill F, Tselepis C (2000) Barrett's metaplasia. Lancet 356:2079–2085

    Article  CAS  PubMed  Google Scholar 

  17. Wijnhoven BP, Tilanus HW, Dinjens WN (2001) Molecular biology of Barrett's adenocarcinoma. Ann Surg 233:322–337

    Article  CAS  PubMed  Google Scholar 

  18. Cheung VG, Morley M, Aguilar F, Massimi A, Kucherlapati R, Childs G (1999) Making and reading microarrays. Nat Genet 21:15–19

    CAS  PubMed  Google Scholar 

  19. Petricoin EF, Hackett JL, Lesko LJ, Puri RK, Gutman SI, Chumakov K, Woodcock J, Feigal DW, Zoon KC, Sistare FD (2002) Medical applications of microarray technologies: a regulatory science perspective. Nat Genet 32 [Suppl 2]:474–479

    Google Scholar 

  20. Selaru FM, Zou T, Xu Y, Shustova V, Yin J, Mori Y, Sato F, Wang S, Olaru A, Shibata D, Greenwald BD, Krasna MJ, Abraham JM, Meltzer SJ (2002) Global gene expression profiling in Barrett's esophagus and esophageal cancer: a comparative analysis using cDNA microarrays. Oncogene 21:475–478

    Article  CAS  PubMed  Google Scholar 

  21. Xu Y, Selaru FM, Yin J, Zou TT, Shustova V, Mori Y, Sato F, Liu TC, Olaru A, Wang S, Kimos MC, Perry K, Desai K, Greenwald BD, Krasna MJ, Shibata D, Abraham JM, Meltzer SJ (2002) Artificial neural networks and gene filtering distinguish between global gene expression profiles of Barrett's esophagus and esophageal cancer. Cancer Res 62:3493–3497

    CAS  PubMed  Google Scholar 

  22. Beer DG, Kardia SL, Huang CC, Giordano TJ, Levin AM, Misek DE, Lin L, Chen G, Gharib TG, Thomas DG, Lizyness ML, Kuick R, Hayasaka S, Taylor JM, Iannettoni MD, Orringer MB, Hanash S (2002) Gene-expression profiles predict survival of patients with lung adenocarcinoma. Nat Med 8:816–824

    CAS  PubMed  Google Scholar 

  23. Tachibana M, Dhar DK, Kinugasa S, Yoshimura H, Fujii T, Shibakita M, Ohno S, Ueda S, Kohno H, Nagasue N (2002) Esophageal cancer patients surviving 6 years after esophagectomy. Langenbecks Arch Surg 387:77–83

    Article  PubMed  Google Scholar 

  24. Eloubeidi MA, Desmond R, Arguedas MR, Reed CE, Wilcox CM (2002) Prognostic factors for the survival of patients with esophageal carcinoma in the U.S.: the importance of tumor length and lymph node status. Cancer 95:1434–1443

    Article  PubMed  Google Scholar 

  25. Gusterson B, Ott R (1990) Occult axillary lymph-node micrometastases in breast cancer. Lancet 336:434–435

    PubMed  Google Scholar 

  26. Pantel K, Cote RJ, Fodstad O (1999) Detection and clinical importance of micrometastatic disease. J Natl Cancer Inst 91:1113–1124

    Article  CAS  PubMed  Google Scholar 

  27. 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 completely resected esophageal cancer. N Engl J Med 337:1188–1194

    Article  CAS  PubMed  Google Scholar 

  28. Vazquez-Sequeiros E, Wang L, Burgart L, Harmsen W, Zinsmeister A, Allen M, Jondal M, Wiersema M (2002) Occult lymph node metastases as a predictor of tumor relapse in patients with node-negative esophageal carcinoma. Gastroenterology 122:1815–1821

    PubMed  Google Scholar 

  29. Matsumoto M, Natsugoe S, Nakashima S, Sakamoto F, Okumura H, Sakita H, Baba M, Takao S, Aikou T (2000) Clinical significance of lymph node micrometastasis of pN0 esophageal squamous cell carcinoma. Cancer Lett 153:189–197

    Article  CAS  PubMed  Google Scholar 

  30. Natsugoe S, Mueller J, Stein HJ, Feith M, Hofler H, Siewert JR (1998) Micrometastasis and tumor cell microinvolvement of lymph nodes from esophageal squamous cell carcinoma: frequency, associated tumor characteristics, and impact on prognosis. Cancer 83:858–866

    Google Scholar 

  31. Sato F, Shimada Y, Li Z, Watanabe G, Maeda M, Imamura M (2001) Lymph node micrometastasis and prognosis in patients with oesophageal squamous cell carcinoma. Br J Surg 88:426–432

    Article  CAS  PubMed  Google Scholar 

  32. Nakamura T, Ide H, Eguchi R, Hayashi K, Ota M, Takasaki K (2002) Clinical implications of lymph node micrometastasis in patients with histologically node-negative (pN0) esophageal carcinoma. J Surg Oncol 79:224–229

    Article  PubMed  Google Scholar 

  33. Pantel K, Braun S, Passlick B, Schlimok G (1996) Minimal residual epithelial cancer: diagnostic approaches and prognostic relevance. Progress in histochemistry and cytochemistry. Fischer, Stuttgart

    Google Scholar 

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

    CAS  PubMed  Google Scholar 

  35. Latza U, Niedobitek G, Schwarting R, Nekarda H, Stein H (1990) Ber-EP4: new monoclonal antibody which distinguishes epithelia from mesothelial. J Clin Pathol 43:213–219

    CAS  PubMed  Google Scholar 

  36. Gottlinger HG, Funke I, Johnson JP, Gokel JM, Riethmuller G (1986) The epithelial cell surface antigen 17-1A, a target for antibody-mediated tumor therapy: its biochemical nature, tissue distribution and recognition by different monoclonal antibodies. Int J Cancer 38:47–53

    CAS  PubMed  Google Scholar 

  37. Hosch SB, Stoecklein NH, Pichlmeier U, Rehders A, Scheunemann P, Niendorf A, Knoefel WT, Izbicki JR (2001) Esophageal cancer: the mode of lymphatic tumor cell spread and its prognostic significance. J Clin Oncol 19:1970–1975

    CAS  PubMed  Google Scholar 

  38. Kubuschok B, Passlick B, Izbicki JR, Thetter O, Pantel K (1999) Disseminated tumor cells in lymph nodes as a determinant for survival in surgically resected non-small-cell lung cancer. J Clin Oncol 17:19–24

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  40. Klein CA, Blankenstein TJ, Schmidt-Kittler O, Petronio M, Polzer B, Stoecklein NH, Riethmuller G (2002) Genetic heterogeneity of single disseminated tumour cells in minimal residual cancer. Lancet 360:683–689

    Article  CAS  PubMed  Google Scholar 

  41. Traweek ST, Liu J, Battifora H (1993) Keratin gene expression in non-epithelial tissues. Detection with polymerase chain reaction. Am J Pathol 142:1111–1118

    CAS  PubMed  Google Scholar 

  42. Mori M, Mimori K, Inoue H, Barnard GF, Tsuji K, Nanbara S, Ueo H, Akiyoshi T (1995) Detection of cancer micrometastases in lymph nodes by reverse transcriptase-polymerase chain reaction. Cancer Res 55:3417–3420

    CAS  PubMed  Google Scholar 

  43. Godfrey TE, Raja S, Finkelstein SD, Gooding WE, Kelly LA, Luketich JD (2001) Prognostic value of quantitative reverse transcription-polymerase chain reaction in lymph node-negative esophageal cancer patients. Clin Cancer Res 7:4041–4048

    CAS  PubMed  Google Scholar 

  44. Raja S, Luketich JD, Kelly LA, Gooding WE, Finkelstein SD, Godfrey TE (2002) Rapid, quantitative reverse transcriptase-polymerase chain reaction: application to intraoperative molecular detection of occult metastases in esophageal cancer. J Thorac Cardiovasc Surg 123:475–482

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank Oleg Schmidt-Kittler for the critical reading of this contribution. N.H.S. is funded by the Deutsche Forschungsgemeinschaft grant STO 464 1-1.

Author information

Authors and Affiliations

  1. Abteilung für Allgemein-, Viszeral- und Thoraxchirurgie, Klinik und Poliklinik für Chirurgie, Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany

    Stefan B. Hosch, Nikolas H. Stoecklein & Jakob R. Izbicki

Authors
  1. Stefan B. Hosch
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nikolas H. Stoecklein
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jakob R. Izbicki
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jakob R. Izbicki.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hosch, S.B., Stoecklein, N.H. & Izbicki, J.R. Molecular markers and staging of early esophageal cancer. Langenbecks Arch Surg 388, 77–82 (2003). https://doi.org/10.1007/s00423-003-0353-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00423-003-0353-y

Keywords

Search

Navigation