Skip to main content

Advertisement

SpringerLink
Log in

Clinical Relevance of Reverse Transcriptase-Polymerase Chain Reaction for the Detection of Axillary Lymph Node Metastases in Breast Cancer

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

Abstract

Background:The mammary sentinel lymph node procedure can increase the detection of axillary metastases by 45% compared with standard axillary dissection. Some investigators have reported that reverse transcriptase-polymerase chain reaction (RT-PCR) increases metastasis detection even more, but it is uncertain whether a positive RT-PCR test in the face of a negative histological evaluation is clinically meaningful.

Methods:RT-PCR for epithelial glycoprotein 2 and cytokeratin 19 was performed on sentinel and pooled nonsentinel axillary lymph nodes from 108 women with clinical stage I or II breast cancer who were followed up for a median of 40 months.

Results:Axillary metastases were detected on standard tissue sections in 26% and by RT-PCR in 30%. Results for the two tests were concordant for 80% of the cases. RT-PCR upstaged 16%. Tumors from women whose lymph nodes were positive only by RT-PCR were phenotypically similar to those from women with no metastases detected by any method. Moreover, 4-year actuarial distant disease-free survival was 100% for women with metastases detected by RT-PCR only, as compared with 74% for those with metastases detected by routine histology (P = .03) and 93% for those with no metastases detected by either method (P = .04).

Conclusions:Analysis of sentinel lymph nodes by RT-PCR for epithelial glycoprotein 2 and cytokeratin 19 is unlikely to provide clinically useful information.

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. Rosen PP, Groshen S, Saigo PE, Kinne DW, Hellman S. A long-term follow-up study of survival in stage I (T1N0M0) and stage II (T1N1M0) breast carcinoma. J Clin Oncol 1989; 7: 355–66.

    CAS  PubMed  Google Scholar 

  2. Cote RJ, Peterson HF, Chaiwun B, et al. Role of immunohistochemical detection of lymph node metastases in management of breast cancer. Lancet 1999; 354: 896–900.

    Article  CAS  PubMed  Google Scholar 

  3. International (Ludwig) Breast Cancer Study Group. Prognostic importance of occult axillary lymph node micrometastases from breast cancers. Lancet 1990; 335: 1565–8.

    Google Scholar 

  4. Wilkenson EJ, Lawrence L, Hause RG, et al. Occult axillary lymph node metastases in invasive breast carcinoma: characteristics of the primary tumor and significance of the metastases. Pathol Annu 1982; 17: 67–90.

    Google Scholar 

  5. Giuliano AE, Dale PS, Turner RR, Morton DL, Evans SW, Krasne DL. Improved axillary staging of breast cancer with sentinel lymphadenectomy. Ann Surg 1995; 222: 394–401.

    CAS  PubMed  Google Scholar 

  6. Traweek ST, Liu J, Battifora H. Keratin gene expression in non-epithelial tissues. Am J Pathol 1993; 142: 1111–8.

    CAS  PubMed  Google Scholar 

  7. Latza U, Niedobitek G, Schwarting R, Nekarda H, Stein H. Ber-Ep4: new monoclonal antibody which distinguishes epithelia from mesothelial. J Clin Pathol 1990; 43: 213–9.

    CAS  PubMed  Google Scholar 

  8. Osborne MP, Asina S, Wong GY, et al. Immunofluorescent monoclonal antibody detection of breast cancer in bone marrow: sensitivity in a model system. Cancer Res 1989; 49: 2510–3.

    CAS  PubMed  Google Scholar 

  9. Cote RJ, Rosen PP, Hakes TB, et al. Monoclonal antibodies detect occult breast cancer metastases in the bone marrow of patients with early stage disease. Am J Surg Pathol 1988; 12: 333–40.

    CAS  PubMed  Google Scholar 

  10. Noguchi S, Aihara T, Nakamori S, et al. The detection of breast carcinoma micrometastases in axillary lymph nodes by means of reverse transcriptase-polymerase chain reaction. Cancer 1994; 74: 1595–600.

    CAS  PubMed  Google Scholar 

  11. Nwariaku F, Euhus DM, Beitsch PD, et al. Sentinel lymph node biopsy: an alternative to elective axillary dissection for breast cancer. Am J Surg Pathol 1998; 176: 529–31.

    CAS  Google Scholar 

  12. Gazdar AF, Oie HK. Re: Martin Brower et al. Growth of cell lines and clinical specimens of human non-small cell lung cancer in a serum-free defined medium. Cancer Res 1986; 46: 6011–2.

    CAS  PubMed  Google Scholar 

  13. Sakaguchi M, Virmani AK, Ashfaq R, et al. Development of a sensitive, specific PCR-based assay for epithelial tumor cells in effusions. Br J Cancer 1999; 79: 416–22.

    CAS  PubMed  Google Scholar 

  14. M Greenwood. The Errors of Sampling Survivorship Tables (Appendix 1. Reports on Public Health and Statistical Subjects, vol 33). London: His Majesty’s Stationary Office, 1926.

  15. Janicke F, Prechtl A, Thomssen C, et al. Randomized adjuvant chemotherapy trial in high-risk, lymph node negative breast cancer patients identified by urokinase-type plasminogen activator and plasminogen activator inhibitor type 1. J Natl Cancer Inst 2001; 93: 913–20.

    CAS  PubMed  Google Scholar 

  16. Redding WH, Monaghan P, Imrie SF, et al. Detection of micrometastases in patients with primary breast cancer. Lancet 1983; 2: 1271–4.

    CAS  PubMed  Google Scholar 

  17. Shammas FV, Van Eekelen JAM, Wee L, Heikkila R, Osland A. Sensitive and quantitative one step polymerase chain reaction using capillary electrophoresis and fluorescence detection for measuring cytokeratin 19 expression. Scand J Clin Lab Invest 1999; 59: 635–42.

    CAS  PubMed  Google Scholar 

  18. Kim HK, Park IA, Heo DS, et al. Cyclin E overexpression as an independent risk factor of visceral relapse in breast cancer. Eur J Surg Oncol 2001; 27: 464–71.

    CAS  PubMed  Google Scholar 

  19. Donnellan R, Kleinschmidt I, Chetty R. Cyclin E immunoexpression in breast ductal carcinoma: pathologic correlations and prognostic implications. Hum Pathol 2001; 32: 89–94.

    CAS  PubMed  Google Scholar 

  20. Giuliano AE, Haigh PI, Brennan MB, et al. Prospective observational study of sentinel lymphadenectomy without further axillary dissection in patients with sentinel node-negative breast cancer. J Clin Oncol 2000; 18: 2553–9.

    PubMed  CAS  Google Scholar 

  21. de Mascarel I, Bonichon F, Coindre JM, Trojani M. Prognostic significance of breast cancer axillary lymph node micrometastases assessed by two special techniques: reevaluation with longer follow-up. Br J Cancer 1992; 66: 523–7.

    CAS  PubMed  Google Scholar 

  22. Savtchenko ES, Schiff TA, Jiang CK, Freedberg IM, Blumenberg M. Embryonic expression of the human 40-kD keratin: evidence from a processed pseudogene sequence. Am J Hum Genet 1988; 43: 630–7.

    CAS  PubMed  Google Scholar 

  23. Schoenfeld A, Luqmani Y, Smith D, et al. Detection of breast cancer micrometastases in axillary lymph nodes by using polymerase chain reaction. Cancer Res 1994; 54: 2986–90.

    CAS  PubMed  Google Scholar 

  24. Ruud P, Fodstad O, Hovig E. Identification of a novel cytokeratin 19 pseudogene that may interfere with reverse transcriptase-polymerase chain reaction assays used to detect metastatic tumor cells. Int J Cancer 1999; 80: 119–25.

    CAS  PubMed  Google Scholar 

  25. Mitas M, Mikhitarian K, Walters C, et al. Quantitative real-time RT-PCR detection of breast cancer micrometastasis using a multigene marker panel. Int J Cancer 2001; 93: 162–71.

    CAS  PubMed  Google Scholar 

  26. Youngson BJ, Cranor M, Rosen PP. Epithelial displacement in surgical breast specimens following needling procedures. Am J Surg Pathol 1994; 18: 896–903.

    Article  CAS  PubMed  Google Scholar 

  27. Youngson BJ, Liberman L, Rosen PP. Displacement of carcinomatous epithelium in surgical breast specimens following stereotactic core biopsy. Am J Clin Pathol 1995; 103: 598–602.

    CAS  PubMed  Google Scholar 

  28. Carter BA, Jensen RA, Simpson JF, Page DL. Benign transport of breast epithelium into axillary nodes after biopsy. Am J Clin Pathol 2000; 113: 259–65.

    CAS  PubMed  Google Scholar 

  29. Masuda N, Tamaki Y, Sakita I, et al. Clinical significance of micrometastases in axillary lymph nodes assessed by reverse transcription-polymerase chain reaction in breast cancer patients. Clin Cancer Res 2000; 6: 4176–85.

    CAS  PubMed  Google Scholar 

  30. Noguchi S, Aihara T, Motomura K, Inaji H, Imaoka S, Koyama H. Histologic characteristics of breast cancers with occult lymph node metastases detected by keratin 19 mRNA reverse transcriptase-polymerase chain reaction. Cancer 1996; 78: 1235–40.

    CAS  PubMed  Google Scholar 

  31. Bostick PJ, Huynh KT, Sarantou T, et al. Detection of metastases in sentinel lymph nodes of breast cancer patients by multiple-marker RT-PCR. Int J Cancer 1998; 79: 645–51.

    CAS  PubMed  Google Scholar 

  32. Manzotti M, Dell’Orto P, Maisonneuve P, Zurrida S, Mazzarol G, Viale G. Reverse transcription-polymerase chain reaction assay for multiple mRNA markers in the detection of breast cancer metastases in sentinel lymph nodes. Int J Oncol 2001; 95: 307–12.

    CAS  Google Scholar 

  33. Lockett MA, Baron PL, O’Brien PH, et al. Detection of occult breast cancer micrometastases in axillary lymph nodes using a multimarker reverse transcriptase-polymerase chain reaction panel. J Am Coll Surg 1998; 187: 9–16.

    CAS  PubMed  Google Scholar 

  34. Noguchi S, Aihara T, Motomura K, Inaji H, Imaoka S, Koyama H. Detection of breast cancer micrometastases in axillary lymph nodes by means of reverse transcriptase-polymerase chain reaction. Comparison between MUC1 mRNA and keratin 19 mRNA amplification. Am J Pathol 1996; 148: 649–56.

    CAS  PubMed  Google Scholar 

  35. Schoenfeld A, Luqmani Y, Sinnett HD, Shousha S, Coombes RC. Keratin 19 mRNA measurement to detect micrometastases in lymph nodes in breast cancer patients. Br J Cancer 1996; 74: 1639–42.

    CAS  PubMed  Google Scholar 

  36. Hoon DSB, Sarantou T, Doi F, et al. Detection of metastatic breast cancer by beta-hCG polymerase chain reaction. Int J Cancer 1996; 69: 369–74.

    CAS  PubMed  Google Scholar 

  37. Aihara T, Fujiwara Y, Ooka M, Sakita I, Tamaki Y, Monden M. Mammoglobin B as a novel marker for detection of breast cancer micrometastases in axillary lymph nodes by reverse transcription-polymerase chain reaction. Br Cancer Res Treat 1999; 58: 137–40.

    CAS  Google Scholar 

  38. Kataoka A, Mori M, Sadanage N, et al. RT-PCR detection of breast cancer cells in sentinel lymph nodes. Int J Oncol 2000; 16: 1147–52.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas

    Marla W. Dudak MD, George N. Peters MD, A. Marilyn Leitch MD & David M. Euhus MD

  2. Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas

    Masahiro Sakaguchi MD, Arvind Virmani PhD, Hossein Saboorian MD & Adi F. Gazdar MD

  3. Division of Surgical Oncology, E6.222, UT Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9155

    David M. Euhus MD

Authors
  1. Masahiro Sakaguchi MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Arvind Virmani PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marla W. Dudak MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. George N. Peters MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. Marilyn Leitch MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hossein Saboorian MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Adi F. Gazdar MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. David M. Euhus MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David M. Euhus MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sakaguchi, M., Virmani, A., Dudak, M.W. et al. Clinical Relevance of Reverse Transcriptase-Polymerase Chain Reaction for the Detection of Axillary Lymph Node Metastases in Breast Cancer. Ann Surg Oncol 10, 117–125 (2003). https://doi.org/10.1245/ASO.2003.01.010

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1245/ASO.2003.01.010

Key Words:

Search

Navigation