Detection of Micrometastasis in Sentinel Lymph Nodes of Patients with Primary Cutaneous Melanoma

  • H.-J. Blaheta
  • B. Schittek
  • H. Breuninger
  • C. Garbe
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 158)

Abstract

The technique of sentinel lymph node (SLN) biopsy has been demonstrated to be highly predictive for the detection of melanoma micrometastases in the regional lymph node basin. Therefore, the SLN was proposed to accurately reflect the lymph node status of patients with primary cutaneous melanoma. As the regional lymph node status is one of the most powerful predictors of survival in patients with primary melanoma, the histopathologic assessment is critically important for accurate staging. In approximately 20% (ranging from 9% to 42%) of patients with primary melanoma, the SLN was found to be tumor-positive by histopathology or immunohistochemistry. However, the true incidence of metastatic melanoma cells in (sentinel) lymph nodes is underestimated by histopathologic examination. Recently, the method of reverse transcription-polymerase chain reaction (RT-PCR) for tyrosinase mRNA has been used as a molecular marker for the presence of melanoma cells. Tyrosinase RT-PCR was demonstrated to significantly increase the detection of melanoma cells in SLNs as compared to histopathology. All lymph nodes positive by histopathology were shown to express tyrosinase by RT-PCR. Furthermore, tyrosinase transcripts were also detected in 36–52% of stage I and II melanoma patients with SLNs negative by histopathology. Importantly, the recurrence rate was significantly higher in patients with histologically negative SLNs who were found to be positive by RT-PCR than in patients with negative results by both techniques. These findings indicate that RT-PCR status of the SLN is more sensitive for detection of minimal melanoma disease than histopathology. Therefore, the RT-PCR status of the SLN may be suitable to improve melanoma staging and may serve as a prognostic factor in patients with primary cutaneous melanoma.

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References

  1. Albertini JJ, Cruse CW, Rapaport D, Wells K, Ross M, DeConti R, Berman CG, Jared K, Messina J, Lyman G, Glass F, Fenske N, Reintgen DS (1996) Intraoperative radiolymphoscintigraphy improves sentinel lymph node identification for patients with melanoma. Ann Surgery 223: 217–224CrossRefGoogle Scholar
  2. Balch CM, Soong S, Shaw HM, Urist MM, and McCarthy SW (1992) An analysis of prognostic factors in 8500 patients with cutaneous melanoma. In: Balch C (ed) ed 2. JB Lippincott, Philadelphia, Cutaneous melanoma 165–187Google Scholar
  3. Balch CM, Soong SJ, Bartolucci AA, Urist MM, Karakousis CP, Smith TJ, Temple WJ, Ross MI, Jewell WR, Mihm MC, Barnhill RL, Wanebo HJ (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: 255–263PubMedCrossRefGoogle Scholar
  4. Bautista NC, Cohen S, Anders KH (1994) Benign melanocytic nevus cells in axillary lymph nodes. A prospective incidence and immunohistochemical study with literature review. Am J Clin Pathol 102: 102–108PubMedGoogle Scholar
  5. Blaheta H-J, Schittek B, Breuninger H, Maczey E, Kroeber S, Sotlar K, Ellwanger U, Thelen MH, Rassner G, Bultmann B, Garbe C (1998) Lymph node micrometastases of cutaneous melanoma: Increased sensitivity of molecular diagnosis in comparison to immunohistochemistry. Int J Cancer 79: 318–323CrossRefGoogle Scholar
  6. Blaheta H-J, Schittek B, Breuninger H, Sotlar K, Ellwanger U, Thelen MH, Mazcey E, Rassner G, Bueltmann B, Garbe C (1999) Detection of melanoma micrometastasis in sentinel nodes by RT-PCR correlates with tumor thickness and is predictive for micrometastatic disease in the lymph node basin. Am J Surg Pathol 23: 822–828PubMedCrossRefGoogle Scholar
  7. Bostick PJ, Morton DL, Turner RR, Huynh KT, Wang HJ, Elashoff R, Essner R, Hoon DSB (1999) Prognostic significance of occult metastases detected by sentinel lymphadenectomy and reverse transcriptase-polymerase chain reaction in early-stage melanoma patients. J Clin Oncol 17: 3238–3244PubMedGoogle Scholar
  8. Breslow A (1970) Thickness, cross-sectional areas and depth of invasion in the prognosis of cutaneous melanoma. Ann Surg 172: 902–908PubMedCrossRefGoogle Scholar
  9. Busam KJ, Chen YT, Old LJ, Stockert E, Iversen K, Coplan KA, Rosai J, Barnhill RL, Jungbluth AA (1998) Expression of Melan-A ( MARTI) in benign melanocytic nevi and primary cutaneous malignant melanoma. Am J Surg Pathol 22: 976–982PubMedCrossRefGoogle Scholar
  10. Buettner P, Garbe C, Bertz J, Burg G, d’Hoedt B, Drepper H, Guggenmoos Holzmann I, Lechner W, Lippold A, Orfanos CE et al. (1995) Primary cutaneous melanoma. Optimized cutoff points of tumor thickness and importance of Clark’s level for prognostic classification. Cancer 75: 2499–2506CrossRefGoogle Scholar
  11. Buzaid AC, Tinoco L, Ross MI, Legha SS, Benjamin RS (1995) Role of computed tomography in the staging of patients with local-regional metastases of melanoma. J Clin Oncol 13: 2104–2108PubMedGoogle Scholar
  12. Cochran AJ, Wen DR, Morton DL (1988) Occult tumor cells in the lymph nodes of patients with pathological stage I malignant melanoma. An immunohistological study. Am J Surg Pathol 12: 612–618PubMedCrossRefGoogle Scholar
  13. Colombari R, Bonetti F, Zamboni G, Scarpa A, Marino F, Tomezzoli A, Capelli P, MenestriL na F, Chilosi M, Fiore DL (1988) Distribution of melanoma specific antibody (HMB-45) in benign and malignant melanocytic tumours. An immunohistochemical study on paraffin sections. Virchows Arch A Pathol Anat Histopathol 413: 17–24PubMedCrossRefGoogle Scholar
  14. Fetsch PA, Marincola FM, Filie A, Hijazi YM, Kleiner DE, Abati A (1999) Melanoma-associated antigen recognized by T cells (MART-1) - The advent of a preferred immunocytochemical antibody for the diagnosis of metastatic malignant melanoma with fine-needle aspiration. Cancer Cytopathol 87: 37–42Google Scholar
  15. Garbe C, Buettner P, Bertz J, Burg G, d’Hoedt B, Drepper H, Guggenmoos-Holzmann I, Lechner W, Lippold A, Orfanos CE (1995) Primary cutaneous melanoma. Identification of prognostic groups and estimation of individual prognosis for 5093 patients. Cancer 75: 2484–2491PubMedCrossRefGoogle Scholar
  16. Gershenwald JE, Thompson W, Mansfield PF, Lee JE, Colome MI, Tseng CH, Lee JJ, Balch CM, Reintgen DS, Ross MI (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: 976–983PubMedGoogle Scholar
  17. Glass LF, Messina JL, Cruse W, Wells K, Rapaport D, Miliotes G, Berman C, Reintgen D, Fenske NA (1996) The use of intraoperative radiolymphoscintigraphy for sentinel node biopsy in patients with malignant melanoma. Dermatol Surg 22: 715–720PubMedCrossRefGoogle Scholar
  18. Gogel BM, Kuhn JA, Ferry KM, Fisher TL, Preskitt JT, O’ Brien JC, Lieberman ZH, Stephens JS, Krag DN (1998) Sentinel lymph node biopsy for melanoma. Am J Surg 176: 544–547PubMedCrossRefGoogle Scholar
  19. Gown AM, Vogel AM, Hoak D, Gough F, McNutt MA (1986) Monoclonal antibodies specific for melanocytic tumors distinguish subpopulations of melanocytes. Am J Pathol 123: 195–203PubMedGoogle Scholar
  20. Hatta N, Fujimoto A, Takehara K, Takata M (1999) Mapping of occult melanoma micrometastases in the inguinal lymph node basin by immunohistochemistry and RT-PCR. Melanoma Res 9: 401–406PubMedCrossRefGoogle Scholar
  21. Hatta N, Takata M, Takehara K, Ohara K (1998) Polymerase chain reaction and immunohistochemistry frequently detect occult melanoma cells in regional lymph nodes of melanoma patients. J Clin Pathol 51: 597–601PubMedCrossRefGoogle Scholar
  22. Jungbluth AA, Busam KJ, Gerald WL, Stockert E, Coplan KA, Iversen K, MacGregor DP, Old LJ, Chen YT (1998) A103: An anti-Melan-A monoclonal antibody for the detection of malignant melanoma in paraffin-embedded tissues. Am J Surg Pathol 22: 595–602Google Scholar
  23. Kageshita T, Kawakami Y, Hirai S, Ono T (1997) Differential expression of MART-1 in primary and metastatic melanoma lesions. J Immunother 20: 460–465PubMedCrossRefGoogle Scholar
  24. Krag DN, Meijer SJ, Weaver DL, Loggie BW, Harlow SP, Tanabe KK, Laughlin EH, Alex JC (1995) Minimal-access surgery for staging of malignant melanoma. Arch Surg 130: 654–658PubMedGoogle Scholar
  25. Kwon BS, Haq AK, Pomerantz SH, Halaban R (1987) Isolation and sequence of a cDNA clone for human tyrosinase that maps at the mouse c-albino locus. Proc Natl Acad Sci USA 84: 7473–7477PubMedCrossRefGoogle Scholar
  26. Leong SPL, Steinmetz I, Habib FA, McMillan A, Gans JZ, Allen RE, Morita ET, ElKadi M, Epstein HD, KashaniSabet M, Sagebiel RW (1997) Optimal selective sentinel lymph node dissection in primary malignant melanoma. Arch Surg 132: 666–673PubMedGoogle Scholar
  27. Lukowsky A, Bellmann B, Ringk A, Winter H, Audring H, Fenske S, Sterry W (1999) Detection of melanoma micrometastases in the sentinel lymph node and in nonsentinel nodes by tyrosinase polymerase chain reaction. J Invest Dermatol 113: 554–559PubMedCrossRefGoogle Scholar
  28. Morton DL, Wen DR, Foshag LJ, Essner R, Cochran A (1993) Intraoperative lymphatic mapping and selective cervical lymphadenectomy for early-stage melanomas of the head and neck. J Clin Oncol 11: 1751–1756PubMedGoogle Scholar
  29. Morton DL, Wen DR, Wong JH, Economou JS, Cagle LA, Storm FK, Foshag LJ, Cochran AJ (1992) Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg 127: 392–399PubMedGoogle Scholar
  30. MrazGernhard S, Sagebiel RW, KashaniSabet M, Miller JR, Leong SPL (1998) Prediction of sentinel lymph node micrometastasis by histological features in primary cutaneous malignant melanoma. Arch Dermatol 134: 983–987CrossRefGoogle Scholar
  31. Pijpers R, Collet GJ, Meijer S, Hoekstra OS (1995) The impact of dynamic lymphoscintigraphy and gamma probe guidance on sentinel node biopsy in melanoma. Eur J Nuc1 Med 22: 1238–1241CrossRefGoogle Scholar
  32. Reintgen D, Cruse CW, Wells K, Berman C, Fenske N, Glass F, Schroer K, Heller R, Ross M, Lyman G et al. (1994) The orderly progression of melanoma nodal metastases. Ann Surg 220: 759–767PubMedCrossRefGoogle Scholar
  33. Schwuerzer-Voit M, Proebstle TM, Sterry W (1996) Identification of lymph node metastases by use of polymerase chain reaction (PCR) in melanoma patients. Eur J Cancer 32 A: 264–268CrossRefGoogle Scholar
  34. Shivers SC, Wang XN, Li WG, Joseph E, Messina J, Glass LF, DeConti R, Cruse CW, Berman C, Fenske NA, Lyman GH, Reintgen DS (1998) Molecular staging of malignant melanoma: Correlation with clinical outcome. JAMA 280: 1410–1415PubMedCrossRefGoogle Scholar
  35. Thompson JF, McCarthy WH, Bosch CM, O’Brien CJ, Quinn MJ, Paramaesvaran S, Crotty K, McCarthy SW, Uren RF, Howman Giles R (1995) Sentinel lymph node status as an indicator of the presence of metastatic melanoma in regional lymph nodes. Melanoma Res 5: 255–260PubMedCrossRefGoogle Scholar
  36. Van der Velde-Zimmermann D, Roijers JF, Bouwens Rombouts A, De Weger RA, De Graaf PW, Tilanus MG, Van den Tweel JG (1996) Molecular test for the detection of tumor cells in blood and sentinel nodes of melanoma patients. Am J Pathol 149: 759–764PubMedGoogle Scholar
  37. Wang X, Heller R, VanVoorhis N, Cruse CW, Glass F, Fenske N, Berman C, Leo Messina J, Rappaport D, Wells K et al. (1994) Detection of submicroscopic lymph node metastases with polymerase chain reaction in patients with malignant melanoma. Ann Surg 220: 768–774PubMedCrossRefGoogle Scholar
  38. Yu LL, Flotte TJ, Tanabe KK, Gadd MA, Cosimi AB, Sober AJ, Mihm MC, Duncan LM (1999) Detection of microscopic melanoma metastases in sentinel lymph nodes. Cancer 86: 617–627PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin · Heidelberg 2001

Authors and Affiliations

  • H.-J. Blaheta
    • 1
  • B. Schittek
    • 1
  • H. Breuninger
    • 1
  • C. Garbe
    • 1
  1. 1.Department of Dermatology, Section of Dermatological OncologyEberhard-Karls-UniversityTübingenGermany

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