Annals of Surgical Oncology

, Volume 11, Issue 4, pp 362–374 | Cite as

Lymphatic Mapping in the Molecular Era

  • Timothy M. Pawlik
  • Merrick I. Ross
  • Jeffrey E. Gershenwald
Educational Review

Key Words:

Sentinel lymph node Melanoma Serial sectioning Immunohistochemistry PCR 


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  1. 1.
    Thompson JF, McCarthy WH, Bosch CMJ. Sentinel lymph node status as an indicator of the presence of metastatic melanoma in regional lymph nodes. Melanoma Res 1995; 5: 255–60.PubMedCrossRefGoogle Scholar
  2. 2.
    Gogel BM, Kuhn JA, Ferry KM, et al. Sentinel lymph node biopsy for melanoma. Am J Surg 1998; 176: 544–7.PubMedCrossRefGoogle Scholar
  3. 3.
    Morton DL, Thompson JF, Essner R, et al. 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 1999; 230: 453–63;discussion 63–5.PubMedCrossRefGoogle Scholar
  4. 4.
    Jansen L, Nieweg OE, Peterse JL, Hoefnagel CA, Valdes Olmos RA, Kroon BBR. Reliability of sentinel lymph node biopsy for staging melanoma. Br J Surg 2000; 87: 484–9.PubMedCrossRefGoogle Scholar
  5. 5.
    Carcoforo P, Soliani G, Bergossi L, et al. Reliability and accuracy of sentinel node biopsy in cutaneous malignant melanoma. Tumori 2002; 88: S14–6.PubMedGoogle Scholar
  6. 6.
    Gershenwald JE, Thompson W, Mansfield PF, et al. 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 1999; 17: 976–83.PubMedGoogle Scholar
  7. 7.
    Ferrone CR, Panageas KS, Busam K, Brady MS, Coit DG. Multivariate prognostic model for patients with thick cutaneous melanoma: importance of sentinel lymph node status. Ann Surg Oncol 2002; 9: 637–45.PubMedGoogle Scholar
  8. 8.
    Cochran AJ. The pathologist’s role in sentinel lymph node evaluation. Semin Nucl Med 2000; 30: 11–7.PubMedCrossRefGoogle Scholar
  9. 9.
    Prieto VG, Clark SH. Processing of sentinel lymph nodes for detection of metastatic melanoma. Ann Diagn Pathol 2002; 6: 257–64.PubMedCrossRefGoogle Scholar
  10. 10.
    Snow H. Melanotic cancerous disease. Lancet 1892; 2: 872–4.Google Scholar
  11. 11.
    Balch CM, Soong S-J, Murad TM, Ingalls AL, Maddox WA. A multifactorial analysis of melanoma: III. Prognostic factors in melanoma patients with lymph node metastases (stage II). Ann Surg 1981; 193: 377–88.PubMedCrossRefGoogle Scholar
  12. 12.
    Reintgen DS, Cox EB, McCarty KSJ, Vollmer RT, Seigler HF. Efficacy of elective lymph node dissection in patients with intermediate thickness primary melanoma. Ann Surg 1983; 198: 379–85.PubMedCrossRefGoogle Scholar
  13. 13.
    McCarthy WH, Shaw HM, Milton GW. Efficacy of elective lymph node dissection in 2,347 patients with clinical stage I malignant melanoma. Surg Gynecol Obstet 1985; 161: 575–80.PubMedGoogle Scholar
  14. 14.
    Morton DL, Wanek L, Nizze JA, Elashoff RM, Wong JH. 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 1991; 214: 491–501.PubMedCrossRefGoogle Scholar
  15. 15.
    Balch CM, Milton GW, Cascinelli N, Sim FH. Elective lymph node dissection: pros and cons. In: Balch CM, Houghton AN, Milton GW, et al., eds. Cutaneous Melanoma. Philadelphia: Lippincott, 1992: 345–66.Google Scholar
  16. 16.
    Sim FH, Taylor WF, Pritchard DJ, Soule EH. Lymphadenectomy in the management of stage I malignant melanoma: a prospective randomized study. Mayo Clin Proc 1986; 61: 697–705.PubMedGoogle Scholar
  17. 17.
    Veronesi U, Adamus J, Bandiera DC, et al. Inefficacy of immediate node dissection in stage I melanoma of the limbs. N Engl J Med 1977; 297: 627–30.PubMedCrossRefGoogle Scholar
  18. 18.
    Veronesi U, Adamus J, Bandiera DC, et al. Delayed regional lymph node dissection in stage I melanoma of the skin of the lower extremities. Cancer 1982; 49: 2420–30.PubMedCrossRefGoogle Scholar
  19. 19.
    Balch CM, Soong S-J, Bartoluccci AA, et al. 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 1996; 224: 255–66.PubMedCrossRefGoogle Scholar
  20. 20.
    Cascinelli N, Morabito A, Santinami M, Mackie RM, Belli F. Immediate or delayed dissection of regional nodes in patients with melanoma of the trunk: a randomised trial. Lancet 1998; 351: 793–6.PubMedCrossRefGoogle Scholar
  21. 21.
    Balch CM, Buzaid AC, Atkins MB, Cascinelli N, Coit DG, Fleming ID. A new American Joint Committee on Cancer staging system for cutaneous melanoma. Cancer 2000; 88: 1484–91.PubMedCrossRefGoogle Scholar
  22. 22.
    Morton DL, Wen DR, Wong JH, et al. Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg 1992; 127: 392–9.PubMedGoogle Scholar
  23. 23.
    Ross MI, Reintgen DS, Balch CM. Selective lymphadenectomy: emerging role for lymphatic mapping and sentinel node biopsy in the management of early stage melanoma. Semin Surg Oncol 1993; 9: 219–23.PubMedGoogle Scholar
  24. 24.
    Gershenwald JE, Tseng CH, Thompson W, et al. Improved sentinel lymph node localization in patients with primary melanoma with the use of radiolabeled colloid. Surgery 1998; 124: 203–10.PubMedGoogle Scholar
  25. 25.
    Krag DN, Meijer SJ, Weaver DL. Minimal-access surgery for staging of malignant melanoma. Arch Surg 1995; 130: 654–60.PubMedGoogle Scholar
  26. 26.
    Ross MI. The case for elective lymphadenectomy. Surg Oncol Clin North Am 1992; 1: 205.Google Scholar
  27. 27.
    Thompson JF. The Sydney Melanoma Unit experience of sentinel lymphadenectomy for melanoma. Ann Surg Oncol 2001; 8 (9 Suppl): 44S–47S.PubMedGoogle Scholar
  28. 28.
    Godellas CV, Berman CG, Lyman G. The identification and mapping of melanoma regional nodal metastases: minimally invasive surgery for the diagnosis of nodal metastases. Am Surg 1995; 61: 97–101.PubMedGoogle Scholar
  29. 29.
    Kapteijn BA, Nieweg OE, Liem I, Mooi WJ, Balm AJ, Muller SH. Localizing the sentinel node in cutaneous melanoma: gamma probe detection versus blue dye. Ann Surg Oncol 1997; 4: 156–60.PubMedCrossRefGoogle Scholar
  30. 30.
    Sumner WE III, Ross MI, Mansfield PF, et al. Implications of lymphatic drainage to unusual sentinel lymph node sites in patients with primary cutaneous melanoma. Cancer 2002; 95: 354–60.PubMedCrossRefGoogle Scholar
  31. 31.
    Uren RF, Howman-Giles R, Thompson JF, et al. Interval nodes: the forgotten sentinel nodes in patients with melanoma. Arch Surg 2000; 135: 1168–72.PubMedCrossRefGoogle Scholar
  32. 32.
    Uren RF, Thompson JF, Howman-Giles R. Sentinel nodes. Interval nodes, lymphatic lakes, and accurate sentinel node identification. Clin Nucl Med 2000; 25: 234–6.PubMedCrossRefGoogle Scholar
  33. 33.
    Thompson JF, Uren RF, Shaw HM, et al. Location of sentinel lymph nodes in patients with cutaneous melanoma: new insights into lymphatic anatomy. J Am Coll Surg 1999; 189: 195–204.PubMedCrossRefGoogle Scholar
  34. 34.
    McMasters KM, Chao C, Wong SL, et al. Interval sentinel lymph nodes in melanoma. Arch Surg 2002; 137: 543–7;discussion 7–9.PubMedCrossRefGoogle Scholar
  35. 35.
    Porter GA, Ross MI, Berman RS, Lee JE, Mansfield PF, Gershenwald JE. Significance of multiple nodal basin drainage in truncal melanoma patients undergoing sentinel lymph node biopsy. Ann Surg Oncol 2000; 7: 256–61.PubMedCrossRefGoogle Scholar
  36. 36.
    Glass LF, Messina JL, Cruse W, et al. The use of intraoperative radiolymphoscintigraphy for sentinel node biopsy in patients with malignant melanoma. Dermatol Surg 1996; 22: 715–20.PubMedCrossRefGoogle Scholar
  37. 37.
    Pijpers R, Borgstein PJ, Meijer S, Hoekstra OS, van Hattum LH, Teule GJ. Sentinel node biopsy in melanoma patients: dynamic lymphoscintigraphy followed by intraoperative gamma probe and vital dye guidance. World J Surg 1997; 21: 788–92;discussion 93.PubMedCrossRefGoogle Scholar
  38. 38.
    Albertini JJ, Cruse CW, Rapaport D, Wells K, Ross MI, DeConti R. Intraoperative radio-lymph-scintigraphy improves sentinel lymph node identification for patients with melanoma. Ann Surg 1996; 223: 217–24.PubMedCrossRefGoogle Scholar
  39. 39.
    Harlow SP, Krag DN, Ashikaga T, et al. Gamma probe guided biopsy of the sentinel node in malignant melanoma: a multicentre study. Melanoma Res 2001; 11: 45–55.PubMedCrossRefGoogle Scholar
  40. 40.
    Balch CM, Soong SJ, Gershenwald JE, Thompson JF, Reintgen DS, Cascinelli N. Prognostic factor analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol 2001; 19: 3622–34.PubMedGoogle Scholar
  41. 41.
    McMasters KM, Sondak VK, Lotze MT, Ross MI. Recent advances in melanoma staging and therapy. Ann Surg Oncol 1999; 6: 467–75.PubMedCrossRefGoogle Scholar
  42. 42.
    Zettersten E, Shaikh L, Ramirez R, Kashani-Sabet M. Prognostic factors in primary cutaneous melanoma. Surg Clin North Am 2003; 83: 61–75.PubMedCrossRefGoogle Scholar
  43. 43.
    Gershenwald JE, Mansfield PF, Lee JE, Ross MI. Role for lymphatic mapping and sentinel lymph node biopsy in patients with thick (> or = 4 mm) primary melanoma. Ann Surg Oncol 2000; 7: 160–5.PubMedCrossRefGoogle Scholar
  44. 44.
    Thompson JF, Shaw HM. The prognosis of patients with thick primary melanomas: is regional lymph node status relevant, and does removing positive regional nodes influence outcome? Ann Surg Oncol 2002; 9: 719–22.PubMedCrossRefGoogle Scholar
  45. 45.
    Balch CM, Buzaid AC, Soong SJ, Atkins MB, Cascinelli N, Coit DG. Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol 2001; 19: 3635–48.PubMedGoogle Scholar
  46. 46.
    Gershenwald JE, Prieto VG, Johnson M. AJCC stage III (nodal) criteria accurately predict survival in sentinel node-positive melanoma patients. Paper presented at: 3rd International Sentinel Node Congress, Yokohama, Japan, 2002.Google Scholar
  47. 47.
    Gershenwald JE, Berman RS, Porter G, Mansfield PF, Lee JE, Ross MI. Regional nodal basin control is not compromised by previous sentinel lymph node biopsy in patients with melanoma. Ann Surg Oncol 2000; 7: 226–31.PubMedCrossRefGoogle Scholar
  48. 48.
    Lee RJ, Gibbs JF, Proulx GM, Kollmorgen DR, Jia C, Kraybill WG. Nodal basin recurrence following lymph node dissection for melanoma: implications for adjuvant radiotherapy. Int J Radiat Oncol Biol Phys 2000; 46: 467–74.PubMedCrossRefGoogle Scholar
  49. 49.
    Pidhorecky I, Lee RJ, Proulx G, et al. Risk factors for nodal recurrence after lymphadenectomy for melanoma. Ann Surg Oncol 2001; 8: 109–15.PubMedCrossRefGoogle Scholar
  50. 50.
    Ballo MT, Strom EA, Zagars GK, et al. Adjuvant irradiation for axillary metastases from malignant melanoma. Int J Radiat Oncol Biol Phys 2002; 52: 964–72.PubMedGoogle Scholar
  51. 51.
    Calabro A, Singletary SE, Balch CM. Patterns of relapse in 1001 consecutive patients with melanoma nodal metastases. Arch Surg 1989; 124: 1051–5.PubMedGoogle Scholar
  52. 52.
    Slingluff CL Jr, Stidham KR, Ricci WM, Stanley WE, Seigler HF. Surgical management of regional lymph nodes in patients with melanoma. Experience with 4682 patients. Ann Surg 1994; 219: 120–30.PubMedCrossRefGoogle Scholar
  53. 53.
    Karakousis CP, Goumas W, Rao U, Driscoll DL. Axillary node dissection in malignant melanoma. Am J Surg 1991; 162: 202–7.PubMedCrossRefGoogle Scholar
  54. 54.
    Roses DF, Provet JA, Harris MN, Gumport SL, Dubin N. Prognosis of patients with pathologic stage II cutaneous malignant melanoma. Ann Surg 1985; 201: 103–7.PubMedCrossRefGoogle Scholar
  55. 55.
    Balch CM. The role of elective lymph node dissection in melanoma: rationale, results, and controversies. J Clin Oncol 1988; 6: 163–72.PubMedGoogle Scholar
  56. 56.
    Morton DL, Wen DR, Foshag LJ. Intraoperative lymphatic mapping and selective cervical lymphadenectomy for early-stage melanoma of the head and neck. J Clin Oncol 1993; 11: 1751–6.PubMedGoogle Scholar
  57. 57.
    Rayatt SS, Hettiaratchy SP, Key A, Powell BW. Psychosocial benefits of sentinel lymph node biopsy in the management of cutaneous malignant melanoma. Br J Plast Surg 2002; 55: 95–9.PubMedCrossRefGoogle Scholar
  58. 58.
    Blumenthal R, Banic A, Brand CU, Ris HB, Lardinois D. Morbidity and outcome after sentinel lymph node dissection in patients with early-stage malignant cutaneous melanoma. Swiss Surg 2002; 8: 209–14.PubMedCrossRefGoogle Scholar
  59. 59.
    Schijven MP, Vingerhoets AJ, Rutten HJ, et al. Comparison of morbidity between axillary lymph node dissection and sentinel node biopsy. Eur J Surg Oncol 2003; 29: 341–50.PubMedCrossRefGoogle Scholar
  60. 60.
    Golshan M, Martin WJ, Dowlatshahi K. Sentinel lymph node biopsy lowers the rate of lymphedema when compared with standard axillary lymph node dissection. Am Surg 2003; 69: 209–11;discussion 12.PubMedGoogle Scholar
  61. 61.
    Wrightson WR, Wong SL, Edwards MJ, et al. Complications associated with sentinel lymph node biopsy for melanoma. Ann Surg Oncol 2003; 10: 676–80.PubMedCrossRefGoogle Scholar
  62. 62.
    Koopal SA, Tiebosch AT, Albertus Piers D, Plukker JT, Schraffordt Koops H, Hoekstra HJ. Frozen section analysis of sentinel lymph nodes in melanoma patients. Cancer 2000; 89: 1720–5.PubMedCrossRefGoogle Scholar
  63. 63.
    Gibbs JF, Huang PP, Zhang PJ, Kraybill WG, Cheney R. Accuracy of pathologic techniques for the diagnosis of metastatic melanoma in sentinel lymph nodes. Ann Surg Oncol 1999; 6: 699–704.PubMedGoogle Scholar
  64. 64.
    Morton LM. Minimally invasive staging of melanoma: invited commentary. J Am Coll Surg 1998; 187: 188–90.CrossRefGoogle Scholar
  65. 65.
    Clary BM, Lewis JJ, Brady MS, Busam K, Coit DG. Should frozen section analysis of the sentinel node be performed in patients with melanoma? Eur J Nucl Med 1999; 26: S68.Google Scholar
  66. 66.
    Tanis PJ, Boom R, Koops HS, et al. Frozen section investigation of the sentinel node in malignant melanoma and breast cancer. Ann Surg Oncol 2001; 8: 222–6.PubMedCrossRefGoogle Scholar
  67. 67.
    Cochran AJ, Wen DR, Morton DL. Occult tumor cells in the lymph nodes of patients with pathological stage I malignant melanoma: an immunohistological study. Am J Surg Pathol 1988; 12: 612–8.PubMedGoogle Scholar
  68. 68.
    Cochran AJ, Huang RR, Guo J, Wen DR. Current practice and future directions in pathology and laboratory evaluation of the sentinel node. Ann Surg Oncol 2001; 8: 13–7.Google Scholar
  69. 69.
    Creager AJ, Shiver SA, Shen P, Geisinger KR, Levine EA. Intraoperative evaluation of sentinel lymph nodes for metastatic melanoma by imprint cytology. Cancer 2002; 94: 3016–22.PubMedCrossRefGoogle Scholar
  70. 70.
    Bieligk SC, Klimstra DS, Rosai J. The detection of micrometastases in melanoma sentinel nodes by step-sectioning and immunohistochemical staining. Melanoma Res 1997; 7: S125.CrossRefGoogle Scholar
  71. 71.
    Bostick PJ, Morton DL, Turner RR, et al. Prognostic significance of occult metastases detected by sentinel lymphadenectomy and reverse transcriptase-polymerase chain reaction in early-stage melanoma patients. J Clin Oncol 1999; 17: 3238–44.PubMedGoogle Scholar
  72. 72.
    Gershenwald JE, Colome MI, Lee JE, Mansfield PF, Tseng CH, Lee JJ. Patterns of recurrence following a negative sentinel lymph node biopsy in 243 patients with stage I or II melanoma. J Clin Oncol 1998; 16: 2253–60.PubMedGoogle Scholar
  73. 73.
    Robert ME, Wen DR, Cochran AJ. Pathological evaluation of the regional lymph nodes in malignant melanoma. Semin Diagn Pathol 1993; 10: 102–15.PubMedGoogle Scholar
  74. 74.
    Reintgen DS, Albertini JJ, Berman CG. Accurate nodal staging of malignant melanoma. Cancer Control 1995; 2: 405–14.PubMedGoogle Scholar
  75. 75.
    Das Gupta TK. Results of treatment of 269 patients with primary cutaneous melanoma: a five-year prospective study. Ann Surg 1977; 186: 201–9.CrossRefGoogle Scholar
  76. 76.
    Saphir O, Amromin G. Obscure axillary lymph node metastasis in carcinoma of the breast. Cancer 1948; 1: 238–41.PubMedCrossRefGoogle Scholar
  77. 77.
    Ruiter DJ, Spatz A, van den Oord JJ, Cook MG. Pathologic staging of melanoma. Semin Oncol 2002; 29: 370–81.PubMedCrossRefGoogle Scholar
  78. 78.
    Reintgen DS, Einstein A. The role of research in cost containment. Cancer Control 1995; 2: 425–31.Google Scholar
  79. 79.
    Cochran AJ. Surgical pathology remains pivotal in the evaluation of ‘sentinel’ lymph nodes. Am Surg Pathol 1999; 23: 1169–72.CrossRefGoogle Scholar
  80. 80.
    Yu LL, Flotte TJ, Tanabe KK, et al. Detection of microscopic melanoma metastases in sentinel lymph nodes. Cancer 1999; 86: 617–27.PubMedCrossRefGoogle Scholar
  81. 81.
    Messina JL, Glass LF, Cruse CW, Berman C, Ku NK, Reintgen DS. Pathologic examination of the sentinel lymph node in malignant melanoma. Am J Surg Pathol 1999; 23: 686–90.PubMedCrossRefGoogle Scholar
  82. 82.
    Baisden BL, Askin FB, Lange JR, Westra WH. HMB-45 immunohistochemical staining of sentinel lymph nodes: a specific method for enhancing detection of micrometastases in patients with melanoma. Am J Surg Pathol 2000; 24: 1140–6.PubMedCrossRefGoogle Scholar
  83. 83.
    Hatta N, Takata M, Takehara K, Ohara K. Polymerase chain reaction and immunohistochemistry frequently detect occult melanoma cells in regional lymph nodes of melanoma patients. J Clin Pathol 1998; 51: 597–601.PubMedCrossRefGoogle Scholar
  84. 84.
    Bachter D, Balda BR, Vogt H, Buchels H. Primary therapy of malignant melanomas: sentinel lymphadenectomy. Int J Dermatol 1998; 37: 278–82.PubMedCrossRefGoogle Scholar
  85. 85.
    Blaheta HJ, Schittek B, Breuninger H, et al. Lymph node micrometastases of cutaneous melanoma: increased sensitivity of molecular diagnosis in comparison to immunohistochemistry. Int J Cancer 1998; 79: 318–23.PubMedCrossRefGoogle Scholar
  86. 86.
    Fisher ER, Swamidoss S, Lee CH, Rockette H, Redmond C, Fisher B. Detection and significance of occult axillary node metastases in patients with invasive breast cancer. Cancer 1978; 42: 2025–31.PubMedCrossRefGoogle Scholar
  87. 87.
    Wells CA, Heryet A, Brochier J, Gatter KC, Mason DY. The immunocytochemical detection of axillary micrometastases in breast cancer. Br J Cancer 1984; 50: 193–7.PubMedGoogle Scholar
  88. 88.
    Thomson W, Mackie RM. Comparison of five antimelanoma antibodies for identification of melanocytic cells on tissue sections in routine dermatopathology. J Am Acad Dermatol 1989; 21: 1280–4.PubMedCrossRefGoogle Scholar
  89. 89.
    Cocchia D, Michetti F, Donato R. Immunochemical and immuno-cytochemical localization of S-100 antigen in normal skin. Nature 1981; 294: 85–7.PubMedCrossRefGoogle Scholar
  90. 90.
    Gaynor R, Irie R, Morton DL, Herschman HR. S100 protein is present in cultured human malignant melanomas. Nature 1980; 286: 400–1.PubMedCrossRefGoogle Scholar
  91. 91.
    van Eldik LJ, Jensen RA, Ehrenfried BA, Whetsell WOJ. Immunohistochemical localization of S100 beta in human nervous system tumors by using monoclonal antibodies with specificity for the S100 beta polypeptide. J Histochem Cytochem 1986; 34: 977–82.PubMedGoogle Scholar
  92. 92.
    Cochran AJ, Wen DR, Herschman HR, Gaynor R. Detection of S-100 protein as an aid to the identification of melanocytic tumors. Cancer 1982; 30: 295–7.Google Scholar
  93. 93.
    Cochran AJ, Holland G, Wen DR, Herschman HR, Lee WR, Straatsma BR. Detection of S-100 protein in the diagnosis of primary and metastatic intraocular tumors. Invest Ophthalmol Vis Sci 1983; 24: 1153–5.PubMedGoogle Scholar
  94. 94.
    Wen DR, Gaynor RB, Cochran AJ. S-100 protein: a marker for melanocytic tumors. Ann N Y Acad Sci 1983; 420: 261–6.PubMedCrossRefGoogle Scholar
  95. 95.
    Cochran AJ, Wen DR, Herschman HR. Occult melanoma in lymph nodes detected by antiserum to S-100 protein. Int J Cancer 1984; 34: 159–63.PubMedCrossRefGoogle Scholar
  96. 96.
    Paul E, Cochran AJ. Immunostaining of tissue sections previously stained with hematoxylin and eosin. Dis Markers 1988; 6: 231–6.PubMedGoogle Scholar
  97. 97.
    Biddle DA, Evans HL, Kemp BL, et al. Intraparenchymal nevus cell aggregates in lymph nodes: a possible diagnostic pitfall with malignant melanoma and carcinoma. Am J Surg Pathol 2003; 27: 673–81.PubMedCrossRefGoogle Scholar
  98. 98.
    Carson KF, Wen DR, Li PX, et al. Nodal nevi and cutaneous melanomas. Am J Surg Pathol 1996; 20: 834–40.PubMedCrossRefGoogle Scholar
  99. 99.
    Prieto VG, Woodruff JM. Expression of HMB45 antigen in spindle cell melanoma. J Cutan Pathol 1997; 24: 580–1.PubMedCrossRefGoogle Scholar
  100. 100.
    Adema GJ, de-Boer AJ, van-’t-Hullenaar R. Melanocyte lineage-specific antigens recognized by monoclonal antibodies NKI-beteb, HMB-50 and HMB-45 are encoded by a single cDNA. Am J Pathol 1993; 143: 1579–85.PubMedGoogle Scholar
  101. 101.
    Adema GJ, de-Boer AJ, Vogel AM. Molecular characterization of the melanocytic lineage-specific antigen gp 100. J Biol Chem 1994; 269: 20126–33.PubMedGoogle Scholar
  102. 102.
    Gooverts G, Buyssens N. Nevus cell maturation or atrophy? Am J Dermatopathol 1988; 10: 20–7.Google Scholar
  103. 103.
    Skelton HG, Smith KJ, Barrett TL. HMB-45 staining in benign and malignant melanocytic lesions. A reflection of cellular activation. Am J Dermatopathol 1991; 13: 543–50.PubMedCrossRefGoogle Scholar
  104. 104.
    Gown AM, Vogel AM, Hoak D. Monoclonal antibodies specific for melanocytic tumours distinguish subpopulations of melanocytes. Am J Pathol 1988; 123: 195–203.Google Scholar
  105. 105.
    Smoller BR, McNutt NS, Hsu A. HMB-45 recognizes stimulated melanocytes. J Cutan Pathol 1989; 16: 49–53.PubMedCrossRefGoogle Scholar
  106. 106.
    Bacchi CE, Bonetti F, Pea M, Martignoni G, Gown AM. HMB-45. A review. Appl Immunohistochem 1996; 4: 73–85.Google Scholar
  107. 107.
    Clarkson KS, Surdgess IC, Molyneux AJ. The usefulness of tyrosinase in the immunohistochemical assessment of melanocytic lesions: a comparison of the novel T311 antibody (anti-tyrosinase) with S-100, HMB-45, and A103 (anti-melan-A). J Clin Pathol 2001; 54: 196–200.PubMedCrossRefGoogle Scholar
  108. 108.
    Cochran AJ, Essner R, Rose DM, Glass EC. Principles of sentinel lymph node identification: background and clinical implications. Langenbecks Arch Surg 2000; 385: 252–60.PubMedCrossRefGoogle Scholar
  109. 109.
    Mahmood MN, Lee MW, Linden MD, Nathanson SD, Hornyak TJ, Zarbo RJ. Diagnostic value of HMB-45 and anti-Melan A staining of sentinel lymph nodes with isolated positive cells. Mod Pathol 2002; 15: 1288–93.PubMedCrossRefGoogle Scholar
  110. 110.
    Jungbluth A, Busam K, Gerald W, et al. A103: an anti-melan-A monoclonal antibody for the detection of malignant melanoma in paraffin-embedded tissues. Am J Surg Pathol 1998; 22: 595–602.PubMedCrossRefGoogle Scholar
  111. 111.
    Blessing K, Sanders D, Grant J. Comparison of immunohistochemical staining of the novel antibody melan-A with S100 protein and HMB-45 in malignant melanoma and melanoma variants. Histopathology 1998; 32: 139–46.PubMedCrossRefGoogle Scholar
  112. 112.
    Brasseur F, Rimoldi D, Lienard D, et al. Expression of MAGE genes in primary and metastatic cutaneous melanoma. Int J Cancer 1995; 63: 375–80.PubMedCrossRefGoogle Scholar
  113. 113.
    Kwon BS. Pigmentation genes: the tyrosinase gene family and the pmel 17 gene family. Invest Dermatol 1993; 100: 134–40.CrossRefGoogle Scholar
  114. 114.
    Hofbauer GF, Kamarashev J, Geertsen R. Tyrosinase immunoreactivity in formalin-fixed, paraffin-embedded primary and metastatic melanoma: frequency and distribution. J Cutan Pathol 1998; 25: 204–9.PubMedCrossRefGoogle Scholar
  115. 115.
    Kaufman O, Koch S, Burghardt J. Tyrosinase, melan-A, and KBA62 as markers for the immunohistochemical identification of metastatic amelanotic melanomas on paraffin sections. Mod Pathol 1998; 11: 740–6.Google Scholar
  116. 116.
    Sarantou T, Chi DDJ, Garrison DA. Melanoma-associated antigens as messenger RNA detection markers for melanoma. Cancer Res 1997; 57: 1371–6.PubMedGoogle Scholar
  117. 117.
    Smith B, Selby P, Southgate J. Detection of melanoma cells in peripheral blood by means of reverse transcriptase and polymerase chain reaction. Lancet 1991; 338: 1227–9.PubMedCrossRefGoogle Scholar
  118. 118.
    Shivers SC, Wang X, Li W, et al. Molecular staging of malignant melanoma: correlation with clinical outcome. JAMA 1998; 280: 1410–5.PubMedCrossRefGoogle Scholar
  119. 119.
    Wang X, Heller R, Van Voorhis N. Detection of submicroscopic lymph node metastases with polymerase chain reaction in patients with malignant melanoma. Ann Surg 1994; 220: 768–74.PubMedCrossRefGoogle Scholar
  120. 120.
    Fields KK, Elfenbein GJ, Trudeau WL. Clinical significance of bone marrow metastases detected using the polymerase chain reaction in patients with breast cancer undergoing high-dose chemotherapy and autologous bone marrow transplants. J Clin Oncol 1996; 6: 1868–76.Google Scholar
  121. 121.
    Neumaier M, Gerhard M, Wagener C. Diagnosis of micrometastases by the amplification of tissue-specific genes. Gene 1995; 159: 43–7.PubMedCrossRefGoogle Scholar
  122. 122.
    Dingemans AM, Brakenhoff RH, Postmus PE, Giaccone G. Detection of cytokeratin-19 transcripts by reverse transcriptase-polymerase chain reaction in lung cancer cell lines and blood of lung cancer patients. Lab Invest 1997; 77: 213–20.PubMedGoogle Scholar
  123. 123.
    Davids V, Kidson SH, Hanekom GS. Accurate molecular detection of melanoma nodal metastases: an assessment of multimarker assay specificity, sensitivity, and detection rate. Mol Pathol 2003; 56: 43–51.PubMedCrossRefGoogle Scholar
  124. 124.
    Kwon BS, Haq AK, Pomerantz SH, Halaban R. Isolation and sequence of a cDNA clone for human tyrosinase that maps at the mouse c-albino locus. Proc Natl Acad Sci U S A 1987; 84: 7473–7.PubMedCrossRefGoogle Scholar
  125. 125.
    Schwurzer-Voit M, Proebstle TM, Sterry W. Identification of lymph node metastases by use of polymerase chain reaction (PCR) in melanoma patients. Eur J Cancer 1996; 32A: 264–8.PubMedCrossRefGoogle Scholar
  126. 126.
    Goydos JS, Ravikumar TS, Germino FJ, Yudd A, Bancila E. Minimally invasive staging of patients with melanoma: sentinel lymphadenectomy and detection of the melanoma-specific proteins Mart-1 and tyrosinase by reverse transcriptase polymerase chain reaction. J Am Coll Surg 1998; 187: 182–90.PubMedCrossRefGoogle Scholar
  127. 127.
    Blaheta HJ, Schittek B, Breuninger H, et al. Detection of melanoma micrometastasis in sentinel nodes by reverse transcription-polymerase chain reaction correlates with tumor thickness and is predictive of micrometastasis disease in lymph node basin. Am J Surg Pathol 1999; 23: 822–8.PubMedCrossRefGoogle Scholar
  128. 128.
    Li W, Stall A, Shivers SC, et al. Clinical relevance of molecular staging for melanoma: a comparison of RT-PCR and immunohistochemistry staining in sentinel lymph nodes of patients with melanoma. Ann Surg 2000; 231: 795–803.PubMedCrossRefGoogle Scholar
  129. 129.
    Li PX, Cheng L, Wen DR. Demonstration of cytoplasmic tyrosinase mRNA in tissue cultured cells by reverse transcriptase (RT) in situ polymerase chain reaction (PCR) and RT PCR in situ hybridization. Diagn Mol Pathol 1997; 6: 26–33.PubMedCrossRefGoogle Scholar
  130. 130.
    Guo J, Cheng L, Wen DR, Huang RR, Cochran AJ. Demonstration of tyrosinase mRNA in formalin fixed paraffin-embedded archival sections of melanoma, using the reverse transcriptase in situ polymerase chain reaction. Diagn Mol Pathol 1998; 7: 10–5.PubMedCrossRefGoogle Scholar
  131. 131.
    Chelly J, Concordet JP, Kaplan JC, Kahn A. Illegitimate transcription: transcription of any gene in any cell. Proc Natl Acad Sci U S A 1989; 86: 2617–21.PubMedCrossRefGoogle Scholar
  132. 132.
    Battyani Z, Xerri L, Hassoun J, Bonerandi JJ, Grob JJ. Tyrosinase gene expression in human tissues. Pigment Cell Res 1993; 6: 400–5.PubMedCrossRefGoogle Scholar
  133. 133.
    Gutzmer R, Kaspari M, Brodersen JP, et al. Specificity of tyrosinase and HMB45 PCR in the detection of melanoma metastases in sentinel lymph node biopsies. Histopathology 2002; 41: 510–8.PubMedCrossRefGoogle Scholar
  134. 134.
    Brouwenstijn N, Slager EH, Bakker AB, Schreurs MW, Van der Spek CW, Adema GJ. Transcription of the gene encoding melanoma-associated antigen gp100 in tissues and cell lines other than those of the melanocytic lineage. Br J Cancer 1997; 76: 1562–6.PubMedGoogle Scholar
  135. 135.
    Hoon DS, Wang Y, Dale PS. Detection of occult melanoma cells in blood with a multiple-marker polymerase chain reaction assay. J Clin Oncol 1995; 13: 2109–16.PubMedGoogle Scholar
  136. 136.
    van der Velde-Zimmermann D, Roijers JF, Bouwens-Ronbouts A, et al. Molecular test for the detection of tumor cells in blood and sentinel nodes of melanoma patients. Am J Pathol 1996; 149: 759–64.PubMedGoogle Scholar
  137. 137.
    Reintgen D, Balch CM, Kirkwood J, Ross MI. Recent advances in the care of the patient with malignant melanoma. Ann Surg 1997; 225: 1–14.PubMedCrossRefGoogle Scholar
  138. 138.
    Bieligk SC, Ghossein R, Bhattacharya S, Coit DG. Detection of tyrosinase mRNA by reverse transcription-polymerase chain reaction in melanoma sentinel nodes. Ann Surg Oncol 1999; 6: 232–40.PubMedCrossRefGoogle Scholar
  139. 139.
    Eggermont AM, Keilholz U, Testori A, Cook M, Lienard D, Ruiter DJ. The EORTC melanoma group translational research program on prognostic factors and ultrastaging in association with the adjuvant therapy trials in stage II and stage III melanoma. European Organization for Research and Treatment of Cancer. Ann Surg Oncol 2001; 8: 38S–40S.PubMedCrossRefGoogle Scholar
  140. 140.
    Ribuffo D, Gradilone A, Vonella M, et al. Prognostic significance of reverse transcriptase-polymerase chain reaction-negative sentinel nodes in malignant melanoma. Ann Surg Oncol 2003; 10: 396–402.PubMedCrossRefGoogle Scholar
  141. 141.
    Davids V, Kidson SH, Hanekom GS. Melanoma patient staging: histopathological versus molecular evaluation of the sentinel node. Melanoma Res 2003; 13: 313–24.PubMedCrossRefGoogle Scholar
  142. 142.
    Bittner M, Meltzer P, Chen Y, et al. Molecular classification of cutaneous malignant melanoma by gene expression profiling. Nature 2000; 406: 536–40.PubMedCrossRefGoogle Scholar
  143. 143.
    Baldi A, Santini D, De Luca A, Paggi MG. cDNA array technology in melanoma: an overview. J Cell Physiol 2003; 196: 219–23.PubMedCrossRefGoogle Scholar
  144. 144.
    Cochran AJ, Lana AM, Wen DR. Histomorphometry in the assessment of prognosis in stage II malignant melanoma. Am J Surg Pathol 1989; 13: 600–4.PubMedCrossRefGoogle Scholar

Copyright information

© The Society of Surgical Oncology, Inc. 2004

Authors and Affiliations

  • Timothy M. Pawlik
    • 1
  • Merrick I. Ross
    • 1
  • Jeffrey E. Gershenwald
    • 1
    • 2
  1. 1.Department of Surgical OncologyThe University of Texas M. D. Anderson Cancer CenterHouston
  2. 2.Department of Surgical Oncology, Unit 444The University of Texas M. D. Anderson Cancer CenterHouston

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