Skip to main content
SpringerLink
Log in

Impact of sentinel lymphadenectomy on survival in a murine model of melanoma

  • Research paper
  • Published:
Clinical & Experimental Metastasis Aims and scope Submit manuscript

Abstract

Lymphatic mapping and sentinel lymph node biopsy—also termed sentinel lymphadenectomy (SL)—has become a standard of care for patients with primary invasive cutaneous melanoma. This technique has been shown to provide accurate information about the disease status of the regional lymph node basins at risk for metastasis, provide prognostic information, and provide durable regional lymph node control. The potential survival benefit afforded to patients undergoing SL is controversial. Central to this controversy is whether metastasis to regional lymph nodes occurs independent of or prior to widespread hematogenous dissemination. A related area of uncertainty is whether tumor cells residing within regional lymph nodes have increased metastatic potential. We have used a murine model of primary invasive cutaneous melanoma based on injection of B16-BL6 melanoma cells into the pinna to address two questions: (1) does SL plus wide excision of the primary tumor result in a survival advantage over wide excision alone; and (2) do melanoma cells growing within lymph nodes produce a higher incidence of hematogenous metastases than do cells growing at the primary tumor site? We found that SL significantly improved the survival of mice with small primary tumors. We found no difference in the incidence of lung metastases produced by B16-BL6 melanoma cells growing exclusively within regional lymph nodes and cells growing within the pinna.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

ELND:

Elective lymph node dissection

HBSS:

Hank’s balanced saline solution

SL:

Sentinel lymphadenectomy

SLN:

Sentinel lymph node

References

  1. Sim FH, Taylor WF, Pritchard DJ et al (1986) Lymphadenectomy in the management of stage I malignant melanoma: a prospective randomized study. Mayo Clin Proc 61:697–705

    PubMed  CAS  Google Scholar 

  2. Veronesi U, Adamus J, Bandiera DC et al (1977) Inefficacy of immediate node dissection in stage I melanoma of the limbs. N Engl J Med 297:627–630

    Article  PubMed  CAS  Google Scholar 

  3. Veronesi U, Adamus J, Bandiera DC et al (1982) Delayed regional lymph node dissection in stage I melanoma of the skin of the lower extremities. Cancer 49:2420–2430

    Article  PubMed  CAS  Google Scholar 

  4. Balch CM, Soong S-J, Bartoluccci AA et al (1996) Efficacy of an elective regional lymph node dissection of 1 to 4 mm thick melanomas for patients 60 years of age and younger. Ann Surg 224:255–266

    Article  PubMed  CAS  Google Scholar 

  5. Cascinelli N, Morabito A, Santinami M et al (1998) Immediate or delayed dissection of regional nodes in patients with melanoma of the trunk: a randomised trial. Lancet 351:793–796

    Article  PubMed  CAS  Google Scholar 

  6. Morton DL, Wen DR, Wong JH et al (1992) Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg 127:392–399

    Google Scholar 

  7. Alex JC, Krag DN (1993) Gamma-probe guided localization of lymph nodes. Surg Oncol 2(3):137–143

    Article  PubMed  CAS  Google Scholar 

  8. Alex JC, Weaver DL, Fairbank JT et al (1993) Gamma-probe-guided lymph node localization in malignant melanoma. Surg Oncol 2(5):303–308

    Article  PubMed  CAS  Google Scholar 

  9. Ross MI, Reintgen DS, Balch CM (1993) Selective lymphadenectomy: emerging role for lymphatic mapping and sentinel node biopsy in the management of early stage melanoma. Semin Surg Oncol 9:219–223

    PubMed  CAS  Google Scholar 

  10. Dessureault S, Soong SJ, Ross MI et al (2001) Improved staging of node-negative patients with intermediate to thick melanomas (>1 mm) with the use of lymphatic mapping and sentinel lymph node biopsy. Ann Surg Oncol 8(10):766–770

    Article  PubMed  CAS  Google Scholar 

  11. Thompson JF, McCarthy WH, Bosch CM et al (1995) Sentinel lymph node status as an indicator of the presence of metastatic melanoma in regional lymph nodes. Melanoma Res 5(4):255–260

    Article  PubMed  CAS  Google Scholar 

  12. Gershenwald JE, Tseng CH, Thompson W et al (1998) Improved sentinel lymph node localization in patients with primary melanoma with the use of radiolabeled colloid. Surgery 124(2):203–210

    PubMed  CAS  Google Scholar 

  13. Gershenwald JE, Thompson W, Mansfield PF et al (1999) Multi-institutional melanoma lymphatic mapping experience: the prognostic value of sentinel lymph node status in 612 stage I or II melanoma patients. J Clin Oncol 17:976–983

    PubMed  CAS  Google Scholar 

  14. Krag DN, Meijer SJ, Weaver DL (1995) Minimal-access surgery for staging of malignant melanoma. Arch Surg 130:654–660

    PubMed  CAS  Google Scholar 

  15. Gershenwald JE, Colome MI, Lee JE et al (1998) Patterns of recurrence following a negative sentinel lymph node biopsy in 243 patients with stage I or II melanoma. J Clin Oncol 16:2253–2260

    PubMed  CAS  Google Scholar 

  16. Morton DL, Thompson JF, Essner R et al (1999) Validation of the accuracy of intraoperative lymphatic mapping and sentinel lymphadenectomy for early-stage melanoma: a multicenter trial. Multicenter selective lymphadenectomy trial group. Ann Surg 230(4):453–463; discussion 63–5

    Article  PubMed  CAS  Google Scholar 

  17. Thompson JF (2001) The Sydney Melanoma Unit experience of sentinel lymphadenectomy for melanoma. Ann Surg Oncol 8(9 Suppl):44S–47S

    PubMed  CAS  Google Scholar 

  18. Ross MI (1992) The case for elective lymphadenectomy. Surg Oncol Clin North Am 1:205

    Google Scholar 

  19. Kretschmer L, Hilgers R, Mohrle M et al (2004) Patients with lymphatic metastasis of cutaneous malignant melanoma benefit from sentinel lymphonodectomy and early excision of their nodal disease. Eur J Cancer 40(2):212–218

    Article  PubMed  CAS  Google Scholar 

  20. Morton DL, Wanek L, Nizze JA et al (1991) Improved long-term survival after lymphadenectomy of melanoma metastatic to regional nodes: analysis of prognostic factors in 1134 patients from the John Wayne Cancer Institute. Ann Surg 214:491–501

    Article  PubMed  CAS  Google Scholar 

  21. Morton DL, Thompson JF, Cochran AJ et al (2006) Sentinel-node biopsy or nodal observation in melanoma.[see comment][erratum appears in N Engl J Med 2006 Nov 2;355(18):1944]. N Engl J Med 355(13):1307–1317

    Google Scholar 

  22. Ward PM, Weiss L (1989) Metachronous seeding of lymph node metastases in rats bearing the MT-100-TC mammary carcinoma: the effect of elective lymph node dissection. Breast Cancer Res Treat 14(3):315–320

    Article  PubMed  CAS  Google Scholar 

  23. Zeidman I, Buss JM (1954) Experimental studies on the spread of cancer in the lymphatic system. I. Effectiveness of the lymph node as a barrier to the passage of embolic tumor cells. Cancer Res 14(5):403–405

    PubMed  CAS  Google Scholar 

  24. Sleeman JP (2000) The lymph node as a bridgehead in the metastatic dissemination of tumors. Recent Results Cancer Res 157:55–81

    PubMed  CAS  Google Scholar 

  25. Hart IR (1979) The selection and characterization of an invasive variant of the B16 melanoma. Am J Pathol 97(3):587–600

    PubMed  CAS  Google Scholar 

  26. Economides F, Bruley-Rosset M (1976) Effects of the removal of the regional lymph nodes on the survival of mice bearing B 16 melanoma or EAkR lymphosarcoma. Biomedicine 25(10):390–395

    PubMed  CAS  Google Scholar 

  27. Mead MJ, Nathanson SD, Lee M et al (1985) Prophylactic lymphadenectomy for B16 melanoma in C57/BL6 mice: survival based on size and heterogeneous variant of the primary. J Surg Res 38(4):319–327

    Article  PubMed  CAS  Google Scholar 

  28. van de Velde CJ, van Putten LM, Zwaveling A (1977) Effects of regional lymphadenectomy and adjuvant chemotherapy on metastasis and survival in rodent tumour models. Eur J Cancer 13(8):883–895

    PubMed  Google Scholar 

  29. Nathanson SD, Haas GP, Mead MJ et al (1986) Spontaneous regional lymph node metastases of three variants of the B16 melanoma: relationship to primary tumor size and pulmonary metastases. J Surg Oncol 33(1):41–45

    Article  PubMed  CAS  Google Scholar 

  30. Killion JJ, Radinsky R, Fidler IJ (1998) Orthotopic models are necessary to predict therapy of transplantable tumors in mice. Cancer Metastasis Rev 17(3):279–284

    Article  PubMed  Google Scholar 

  31. Edwards JM, Kinmonth JB (1969) Lymphovenous shunts in man. Br Med J 4(683):579–581

    Article  PubMed  CAS  Google Scholar 

  32. Pressman JJ, Simon MB (1961) Experimental evidence of direct communications between lymph nodes and veins. Surg Gynecol Obstet 113:537–541

    PubMed  CAS  Google Scholar 

  33. Barkhordar RA, Berston ED, Ramos DM (1995) Cervical lymph node metastasis: model for study of head/neck melanoma. Eur J Cancer B Oral Oncol 31B(1):49–52

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Author notes

  1. Robert B. Rebhun

    Present address: The Animal Cancer Center, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, 80523, USA

Authors and Affiliations

  1. The Department of Cancer Biology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, 77030, USA

    Robert B. Rebhun, Isaiah J. Fidler & Jeffrey E. Gershenwald

  2. The Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, 77030, USA

    Alexander J. F. Lazar

  3. The Sarcoma Research Center, The University of Texas M. D. Anderson Cancer Center, Houston, TX, 77030, USA

    Alexander J. F. Lazar

  4. Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 444, Houston, TX, 77030, USA

    Jeffrey E. Gershenwald

Authors
  1. Robert B. Rebhun
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alexander J. F. Lazar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Isaiah J. Fidler
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jeffrey E. Gershenwald
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jeffrey E. Gershenwald.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rebhun, R.B., Lazar, A.J.F., Fidler, I.J. et al. Impact of sentinel lymphadenectomy on survival in a murine model of melanoma. Clin Exp Metastasis 25, 191–199 (2008). https://doi.org/10.1007/s10585-008-9141-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10585-008-9141-y

Keywords

Search

Navigation