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
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: 217–224
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 165–187
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: 255–263
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: 102–108
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: 318–323
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: 822–828
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: 3238–3244
Breslow A (1970) Thickness, cross-sectional areas and depth of invasion in the prognosis of cutaneous melanoma. Ann Surg 172: 902–908
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: 976–982
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: 2499–2506
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: 2104–2108
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: 612–618
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: 17–24
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: 37–42
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: 2484–2491
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: 976–983
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: 715–720
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: 544–547
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: 195–203
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: 401–406
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: 597–601
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: 595–602
Kageshita T, Kawakami Y, Hirai S, Ono T (1997) Differential expression of MART-1 in primary and metastatic melanoma lesions. J Immunother 20: 460–465
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: 654–658
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: 7473–7477
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: 666–673
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: 554–559
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: 1751–1756
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: 392–399
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: 983–987
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: 1238–1241
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: 759–767
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: 264–268
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: 1410–1415
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: 255–260
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: 759–764
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: 768–774
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: 617–627
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Blaheta, HJ., Schittek, B., Breuninger, H., Garbe, C. (2001). Detection of Micrometastasis in Sentinel Lymph Nodes of Patients with Primary Cutaneous Melanoma. In: Reinhold, U., Tilgen, W. (eds) Minimal Residual Disease in Melanoma. Recent Results in Cancer Research, vol 158. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-59537-0_14
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DOI: https://doi.org/10.1007/978-3-642-59537-0_14
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