Expression of tyrosinase, MIA and MART-1 in sentinel lymph nodes of patients with malignant melanoma
Summary Background Regional lymph node status is an important predictor of survival in patients with malignant melanoma. Mapping of sentinel lymph nodes using sensitive molecular techniques has recently been introduced. Malignant melanoma is heterogeneous in terms of its biological, immunological an...
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          | Published in | British journal of dermatology (1951) Vol. 146; no. 2; pp. 244 - 249 | 
|---|---|
| Main Authors | , , , , | 
| Format | Journal Article | 
| Language | English | 
| Published | 
        Oxford, UK
          Blackwell Science, Ltd
    
        01.02.2002
     Blackwell Oxford University Press  | 
| Subjects | |
| Online Access | Get full text | 
| ISSN | 0007-0963 1365-2133  | 
| DOI | 10.1046/j.1365-2133.2002.04579.x | 
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| Abstract | Summary Background Regional lymph node status is an important predictor of survival in patients with malignant melanoma. Mapping of sentinel lymph nodes using sensitive molecular techniques has recently been introduced. Malignant melanoma is heterogeneous in terms of its biological, immunological and metastatic properties, and melanoma cells exhibit a polymorphous expression of tumour markers. Thus, assays that include multiple markers appear to be more sensitive than single‐marker assays.
Objectives To characterize the molecular profiles of melanoma cells in sentinel lymph nodes employing the mRNA expression of tyrosinase, MIA and MART‐1 as markers.
Methods Samples of sentinel lymph nodes from 17 melanoma patients and 18 control nodes from non‐melanoma patients were assayed by reverse transcriptase–polymerase chain reaction, using specific primers for each marker.
Results We found that both tyrosinase and MIA expression were sensitive indicators of micrometastases in sentinel lymph nodes that were negative on routine histopathological examination, and that the finding of micrometastases expressing MART‐1 in sentinel lymph nodes was negatively correlated with overall survival.
Conclusions Characterization of the molecular profiles of melanoma cells constitutes a valid means of detecting metastatic melanoma cells in sentinel lymph nodes, and of predicting the survival of melanoma patients. | 
    
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| AbstractList | Summary Background Regional lymph node status is an important predictor of survival in patients with malignant melanoma. Mapping of sentinel lymph nodes using sensitive molecular techniques has recently been introduced. Malignant melanoma is heterogeneous in terms of its biological, immunological and metastatic properties, and melanoma cells exhibit a polymorphous expression of tumour markers. Thus, assays that include multiple markers appear to be more sensitive than single‐marker assays.
Objectives To characterize the molecular profiles of melanoma cells in sentinel lymph nodes employing the mRNA expression of tyrosinase, MIA and MART‐1 as markers.
Methods Samples of sentinel lymph nodes from 17 melanoma patients and 18 control nodes from non‐melanoma patients were assayed by reverse transcriptase–polymerase chain reaction, using specific primers for each marker.
Results We found that both tyrosinase and MIA expression were sensitive indicators of micrometastases in sentinel lymph nodes that were negative on routine histopathological examination, and that the finding of micrometastases expressing MART‐1 in sentinel lymph nodes was negatively correlated with overall survival.
Conclusions Characterization of the molecular profiles of melanoma cells constitutes a valid means of detecting metastatic melanoma cells in sentinel lymph nodes, and of predicting the survival of melanoma patients. Regional lymph node status is an important predictor of survival in patients with malignant melanoma. Mapping of sentinel lymph nodes using sensitive molecular techniques has recently been introduced. Malignant melanoma is heterogeneous in terms of its biological, immunological and metastatic properties, and melanoma cells exhibit a polymorphous expression of tumour markers. Thus, assays that include multiple markers appear to be more sensitive than single-marker assays. To characterize the molecular profiles of melanoma cells in sentinel lymph nodes employing the mRNA expression of tyrosinase, MIA and MART-1 as markers. Samples of sentinel lymph nodes from 17 melanoma patients and 18 control nodes from non-melanoma patients were assayed by reverse transcriptase-polymerase chain reaction, using specific primers for each marker. We found that both tyrosinase and MIA expression were sensitive indicators of micrometastases in sentinel lymph nodes that were negative on routine histopathological examination, and that the finding of micrometastases expressing MART-1 in sentinel lymph nodes was negatively correlated with overall survival. Characterization of the molecular profiles of melanoma cells constitutes a valid means of detecting metastatic melanoma cells in sentinel lymph nodes, and of predicting the survival of melanoma patients. Regional lymph node status is an important predictor of survival in patients with malignant melanoma. Mapping of sentinel lymph nodes using sensitive molecular techniques has recently been introduced. Malignant melanoma is heterogeneous in terms of its biological, immunological and metastatic properties, and melanoma cells exhibit a polymorphous expression of tumour markers. Thus, assays that include multiple markers appear to be more sensitive than single-marker assays.BACKGROUNDRegional lymph node status is an important predictor of survival in patients with malignant melanoma. Mapping of sentinel lymph nodes using sensitive molecular techniques has recently been introduced. Malignant melanoma is heterogeneous in terms of its biological, immunological and metastatic properties, and melanoma cells exhibit a polymorphous expression of tumour markers. Thus, assays that include multiple markers appear to be more sensitive than single-marker assays.To characterize the molecular profiles of melanoma cells in sentinel lymph nodes employing the mRNA expression of tyrosinase, MIA and MART-1 as markers.OBJECTIVESTo characterize the molecular profiles of melanoma cells in sentinel lymph nodes employing the mRNA expression of tyrosinase, MIA and MART-1 as markers.Samples of sentinel lymph nodes from 17 melanoma patients and 18 control nodes from non-melanoma patients were assayed by reverse transcriptase-polymerase chain reaction, using specific primers for each marker.METHODSSamples of sentinel lymph nodes from 17 melanoma patients and 18 control nodes from non-melanoma patients were assayed by reverse transcriptase-polymerase chain reaction, using specific primers for each marker.We found that both tyrosinase and MIA expression were sensitive indicators of micrometastases in sentinel lymph nodes that were negative on routine histopathological examination, and that the finding of micrometastases expressing MART-1 in sentinel lymph nodes was negatively correlated with overall survival.RESULTSWe found that both tyrosinase and MIA expression were sensitive indicators of micrometastases in sentinel lymph nodes that were negative on routine histopathological examination, and that the finding of micrometastases expressing MART-1 in sentinel lymph nodes was negatively correlated with overall survival.Characterization of the molecular profiles of melanoma cells constitutes a valid means of detecting metastatic melanoma cells in sentinel lymph nodes, and of predicting the survival of melanoma patients.CONCLUSIONSCharacterization of the molecular profiles of melanoma cells constitutes a valid means of detecting metastatic melanoma cells in sentinel lymph nodes, and of predicting the survival of melanoma patients.  | 
    
| Author | Lotem, M. Gimon, Z. Hochberg, M. Shiloni, E. Enk, C.D.  | 
    
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| Cites_doi | 10.1097/00000658-199412000-00010 10.1097/00001622-199403000-00012 10.1093/oxfordjournals.bmb.a072979 10.1097/00000658-199111000-00015 10.1097/00008390-199604000-00013 10.1002/(SICI)1097-0142(19960701)78:1<10::AID-CNCR3>3.3.CO;2-T 10.1084/jem.180.1.35 10.1001/archsurg.1992.01420040034005 10.1001/jama.280.16.1410 10.1200/JCO.1995.13.8.2109 10.1056/NEJM199107183250306 10.1002/pros.2990250505 10.1200/JCO.1999.17.8.2562 10.1084/jem.163.1.215 10.1016/0140-6736(91)92100-G 10.1016/0959-8049(96)00182-7 10.1111/j.1600-0749.1989.tb00166.x 10.1097/00000478-199907000-00011 10.1016/S1072-7515(98)00138-0 10.1093/clinchem/42.9.1369 10.1007/978-1-4615-3080-0_8 10.1038/sj.bjc.6690436 10.1093/jnci/88.9.569 10.1046/j.1523-1747.1999.00719.x  | 
    
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| Keywords | Human Polymerase chain reaction Skin disease Prognosis Messenger RNA Sentinel lymph node Malignant melanoma Tumoral marker Skin Malignant tumor Molecular biology Survival  | 
    
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| References | Buzaid AC, Balch CM. Polymerase chain reaction for detection of melanoma in peripheral blood: too early to assess clinical value. J␣Natl Cancer Inst 1996; 88: 569-70. Siegel S. Nonparametric Statistics. New York: McGraw-Hill, 1956: 161-202. Elder DE, Rodeck U, Turin J et al. Antigenic profile of tumor progression stages in human melanocyte nevi and melanomas. Cancer Res 1989; 49: 5091-6. Sarantou T, Chi DDJ, Garrison DA et al. Melanoma-associated antigens as messenger RNA detection markers for melanoma. Cancer Res 1997; 57: 1371-6. Hearing VJ, Jimenez M. Analysis of mammalian pigmentation at the molecular level. Pigment Cell Res 1989; 2: 75-89. Blaheta HJ, Schittec 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 micrometastatic disease in the lymph node basin. Am J Surg Pathol 1999; 23: 822-8. Rankin EM. Detection of early micrometastases in malignant melanoma. Eur J Cancer 1996; 32A: 1627-9. Keilhotz U, Scheibenbogen C, Sommer M et al. Prognostic factors␣for response and survival in patients with metastatic melanoma receiving immunotherapy. Melanoma Res 1996; 6: 173-8. Ghossein RA, Rosai J. Polymerase chain reaction in the detection of micrometastases and circulating tumor cells. Cancer 1996; 78: 10-16. Slominski A, Ross J, Mihms MC. Cutaneous melanoma: pathology, relevant prognostic indicators and progression. Br Med Bull 1995; 51: 548-69. Lingam MK, MacKie RM, Mackay AJ. Intraoperative lymphatic mapping using patent blue V dye to identify nodal micrometastases in malignant melanoma. Reg Cancer Treat 1994; 7: 144-6. Smith B, Selby P, Southgate J et al. Detection of melanoma cells in peripheral blood by means of reverse transcriptase and polymerase chain reaction. Lancet 1991; 338: 1227-9. Blesch A, Bosserhoff AK, Apfel R et al. Cloning of a new malignant melanoma-derived growth regulatory protein, MIA. Cancer Res 1994; 54: 5697-701. Koh HK. Cutaneous melanoma. N Engl J Med 1991; 325: 171-82. Goydos JS, Ravikumar TS, Germino FJ et al. 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. Pelkey TJ, Frierson HF, Bruns DE. Molecular and immunological detection of circulating tumor cells and micrometastases from solid tumors. Clin Chem 1996; 42: 1369-81. Morton DL, Wen DR, Wong JH et al. Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg 1992; 127: 393-9. Anichini A, Fossati G, Parmiani G. Heterogeneity of clones from human metastatic melanoma detected by autologous cytotoxic T-lymphocyte clones. J Exp Med 1986; 163: 215-20. Lukowski A, Bellmann B, Ringk A et al. Detection of melanoma micrometastases in the sentinel lymph node and in nonsentinel nodes by tyrosinase polymerase chain reaction. J Invest Dermatol 1999; 113: 554-9.DOI: 10.1046/j.1523-1747.1999.00719.x Wang X, Heller R, Van Voorhis N et al. Detection of submicroscopic lymph node metastases with polymerase chain reaction in patients with malignant melanoma. Ann Surg 1994; 220: 760-74. Shivers SC, Wang X, Li W et al. Molecular staging of malignant melanoma. Correlation with clinical outcome. JAMA 1998; 280: 1410-15. Wong JH, Cagle LA, Morton DL. Lymphatic drainage of skin to a sentinel lymph node in a feline model. Ann Surg 1991; 214: 637-41. Coulie PG, Brichard V, Van Pel A et al. A new gene coding for a differentiation antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas. J Exp Med 1994; 180: 35-42. Runger TM, Klein CE, Becker JC et al. The role of genetic instability, adhesion, cell motility immune escape mechanisms in melanoma expression. Curr Opin Oncol 1994; 6: 188-96. Curry BJ, Myers K, Hersey P. MART-1 is expressed less frequently on circulating melanoma cells in patients who develop distant compared with locoregional metastases. J Clin Oncol 1999; 17: 2562-71. Rinker-Schaeffer CS, Partin AW, Isaacs WB et al. Molecular and cellular changes associated with the acquisition of metastatic ability by prostatic cancer cells. Prostate 1994; 25: 249-65. Hoon DSB, Wang Y, Dale PS et al. Detection of occult melanoma cells in blood with a multiple-marker polymerase chain reaction assay. J Clin Oncol 1996; 13: 2109-16. De Vries TJ, Fourkour A, Punt CJA et al. Reproducibility of detection of tyrosinase and MART-1 transcript in the peripheral blood of melanoma patients: a quality control study using real-time quantitative RT-PCR. Br J Cancer 1999; 80: 883-91. Albino AP, Fountain JW. Molecular genetics of human malignant melanoma. 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| References_xml | – reference: Smith B, Selby P, Southgate J et al. Detection of melanoma cells in peripheral blood by means of reverse transcriptase and polymerase chain reaction. Lancet 1991; 338: 1227-9. – reference: Lukowski A, Bellmann B, Ringk A et al. Detection of melanoma micrometastases in the sentinel lymph node and in nonsentinel nodes by tyrosinase polymerase chain reaction. J Invest Dermatol 1999; 113: 554-9.DOI: 10.1046/j.1523-1747.1999.00719.x – reference: Slominski A, Ross J, Mihms MC. Cutaneous melanoma: pathology, relevant prognostic indicators and progression. Br Med Bull 1995; 51: 548-69. – reference: Hoon DSB, Wang Y, Dale PS et al. Detection of occult melanoma cells in blood with a multiple-marker polymerase chain reaction assay. J Clin Oncol 1996; 13: 2109-16. – reference: Keilhotz U, Scheibenbogen C, Sommer M et al. Prognostic factors␣for response and survival in patients with metastatic melanoma receiving immunotherapy. Melanoma Res 1996; 6: 173-8. – reference: Albino AP, Fountain JW. Molecular genetics of human malignant melanoma. Cancer Treat Res 1993; 65: 201-55. – reference: Goydos JS, Ravikumar TS, Germino FJ et al. 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. – reference: Sarantou T, Chi DDJ, Garrison DA et al. Melanoma-associated antigens as messenger RNA detection markers for melanoma. Cancer Res 1997; 57: 1371-6. – reference: Blesch A, Bosserhoff AK, Apfel R et al. Cloning of a new malignant melanoma-derived growth regulatory protein, MIA. Cancer Res 1994; 54: 5697-701. – reference: Blaheta HJ, Schittec 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 micrometastatic disease in the lymph node basin. Am J Surg Pathol 1999; 23: 822-8. – reference: Curry BJ, Myers K, Hersey P. MART-1 is expressed less frequently on circulating melanoma cells in patients who develop distant compared with locoregional metastases. J Clin Oncol 1999; 17: 2562-71. – reference: Elder DE, Rodeck U, Turin J et al. Antigenic profile of tumor progression stages in human melanocyte nevi and melanomas. Cancer Res 1989; 49: 5091-6. – reference: Wong JH, Cagle LA, Morton DL. Lymphatic drainage of skin to a sentinel lymph node in a feline model. Ann Surg 1991; 214: 637-41. – reference: Pelkey TJ, Frierson HF, Bruns DE. Molecular and immunological detection of circulating tumor cells and micrometastases from solid tumors. Clin Chem 1996; 42: 1369-81. – reference: Morton DL, Wen DR, Wong JH et al. Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg 1992; 127: 393-9. – reference: Anichini A, Fossati G, Parmiani G. Heterogeneity of clones from human metastatic melanoma detected by autologous cytotoxic T-lymphocyte clones. J Exp Med 1986; 163: 215-20. – reference: De Vries TJ, Fourkour A, Punt CJA et al. Reproducibility of detection of tyrosinase and MART-1 transcript in the peripheral blood of melanoma patients: a quality control study using real-time quantitative RT-PCR. Br J Cancer 1999; 80: 883-91. – reference: Lingam MK, MacKie RM, Mackay AJ. Intraoperative lymphatic mapping using patent blue V dye to identify nodal micrometastases in malignant melanoma. Reg Cancer Treat 1994; 7: 144-6. – reference: Hearing VJ, Jimenez M. Analysis of mammalian pigmentation at the molecular level. Pigment Cell Res 1989; 2: 75-89. – reference: Buzaid AC, Balch CM. Polymerase chain reaction for detection of melanoma in peripheral blood: too early to assess clinical value. J␣Natl Cancer Inst 1996; 88: 569-70. – reference: Shivers SC, Wang X, Li W et al. Molecular staging of malignant melanoma. Correlation with clinical outcome. JAMA 1998; 280: 1410-15. – reference: Siegel S. Nonparametric Statistics. New York: McGraw-Hill, 1956: 161-202. – reference: Wang X, Heller R, Van Voorhis N et al. Detection of submicroscopic lymph node metastases with polymerase chain reaction in patients with malignant melanoma. Ann Surg 1994; 220: 760-74. – reference: Koh HK. Cutaneous melanoma. N Engl J Med 1991; 325: 171-82. – reference: Coulie PG, Brichard V, Van Pel A et al. A new gene coding for a differentiation antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas. J Exp Med 1994; 180: 35-42. – reference: Ghossein RA, Rosai J. Polymerase chain reaction in the detection of micrometastases and circulating tumor cells. 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| Snippet | Summary Background Regional lymph node status is an important predictor of survival in patients with malignant melanoma. Mapping of sentinel lymph nodes using... Regional lymph node status is an important predictor of survival in patients with malignant melanoma. Mapping of sentinel lymph nodes using sensitive molecular...  | 
    
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| SubjectTerms | Adult Antigens, Neoplasm - analysis Antigens, Neoplasm - genetics Biological and medical sciences Biomarkers, Tumor - analysis Dermatology Extracellular Matrix Proteins Female Gene Expression Humans Lymphatic Metastasis - diagnosis Male MART-1 Antigen Medical sciences Melanoma - chemistry Melanoma - diagnosis Melanoma - secondary melanoma markers micrometastases Middle Aged Monophenol Monooxygenase - analysis Monophenol Monooxygenase - genetics Neoplasm Proteins - analysis Neoplasm Proteins - genetics Prognosis Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - genetics RNA, Neoplasm - genetics Sentinel Lymph Node Biopsy sentinel lymph nodes Survival Rate Tumors of the skin and soft tissue. Premalignant lesions  | 
    
| Title | Expression of tyrosinase, MIA and MART-1 in sentinel lymph nodes of patients with malignant melanoma | 
    
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