Impact of molecular staging methods in primary melanoma: reverse-transcriptase polymerase chain reaction (RT-PCR) of ultrasound-guided aspirate of the sentinel node does not improve diagnostic accuracy, but RT-PCR of peripheral blood does predict survival.

PURPOSE This study analyzes (1) the value of tyrosinase reverse-transcriptase polymerase chain reaction (RT-PCR) of aspirates obtained by ultrasound-guided fine-needle aspiration cytology (US-FNAC) of sentinel nodes (SNs) in patients with melanoma before sentinel lymph node biopsy (SLNB) and (2) the value of RT-PCR of blood samples of all SLNB patients. PATIENTS AND METHODS Between 2001 and 2003, 127 patients with melanoma (median Breslow depth, 2.1 mm) underwent SLNB. FNAC was performed in all SNs of all patients pre- and post-SLNB. The aspirates were partly shock-frozen for RT-PCR and were partly used for standard cytology. Peripheral blood was collected at the time of SLNB and at every outpatient visit thereafter. RESULTS Thirty-four (23%) of 120 SNs were positive for melanoma. SN involvement was predicted by US-FNAC with a sensitivity of 82% and a specificity of 72%. Additional tyrosinase RT-PCR revealed the same sensitivity of 82% and a specificity of 72%. At a median follow-up time of 40 months from first blood sample, peripheral-blood RT-PCR was a significant independent predictor of disease-free survival (DFS) and overall survival (OS; P < .001). CONCLUSION US-FNAC is highly accurate and eliminates the need for SLNB in 16% of all SLNB patients. RT-PCR of the aspirate or excised SN does not improve sensitivity or specificity. RT-PCR of blood samples predicts DFS and OS.

[1]  S. Mocellin,et al.  Sentinel lymph node molecular ultrastaging in patients with melanoma: a systematic review and meta-analysis of prognosis. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  P. Quaglino,et al.  What is the role of sequential reverse-transcriptase polymerase chain reaction analysis of melanoma-specific mRNA in the peripheral blood of melanoma patients? , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  Martina Kron,et al.  Ultrasound-guided Fine Needle Aspiration Cytology prior to Sentinel Lymph Node Biopsy in Melanoma Patients , 2006, Annals of Surgical Oncology.

[4]  A. Eggermont,et al.  Clinical relevance of melanoma micrometastases (<0.1 mm) in sentinel nodes: are these nodes to be considered negative? , 2006, Annals of oncology : official journal of the European Society for Medical Oncology.

[5]  R. Elashoff,et al.  Sentinel-node biopsy or nodal observation in melanoma. , 2006, The New England journal of medicine.

[6]  Angela M Lewis,et al.  Prospective multi-institutional study of reverse transcriptase polymerase chain reaction for molecular staging of melanoma. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  A. Y. de Kanter,et al.  Reasons for failure to identify positive sentinel nodes in breast cancer patients with significant nodal involvement. , 2006, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[8]  A. Eggermont,et al.  High positive sentinel node identification rate by EORTC melanoma group protocol. Prognostic indicators of metastatic patterns after sentinel node biopsy in melanoma. , 2006, European journal of cancer.

[9]  W. Sterry,et al.  Molecular staging in stage II and III melanoma patients and its effect on long-term survival. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  A. Eggermont Reducing the Need for Sentinel Node Procedures by Ultrasound Examination of Regional Lymph Nodes , 2005, Annals of Surgical Oncology.

[11]  M. Green,et al.  The microanatomic location of metastatic melanoma in sentinel lymph nodes predicts nonsentinel lymph node involvement. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  P. Quaglino,et al.  Tyrosinase expression in the peripheral blood of stage III melanoma patients is associated with a poor prognosis: a clinical follow-up study of 110 patients , 2003, British Journal of Cancer.

[13]  R. Elashoff,et al.  Lymphatic Mapping and Sentinel Lymphadenectomy for Early-Stage Melanoma: Therapeutic Utility and Implications of Nodal Microanatomy and Molecular Staging for Improving the Accuracy of Detection of Nodal Micrometastases , 2003, Annals of surgery.

[14]  R. Turner,et al.  Prediction of disease outcome in melanoma patients by molecular analysis of paraffin-embedded sentinel lymph nodes. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  A. Eggermont,et al.  The development of optimal pathological assessment of sentinel lymph nodes for melanoma , 2003, The Journal of pathology.

[16]  W. Sterry,et al.  The role of ultrasound in detection and management of regional disease in melanoma patients. , 2002, Seminars in oncology.

[17]  E. Thiel,et al.  Quantitative nested real-time RT-PCR specific for tyrosinase transcripts to quantitate minimal residual disease. , 2002, Clinica chimica acta; international journal of clinical chemistry.

[18]  E. Thiel,et al.  Reliability of PCR-based detection of occult tumour cells: lessons from real-time RT-PCR , 2001, Melanoma research.

[19]  W. Sterry,et al.  Efficacy of ultrasound B‐scan compared with physical examination in follow‐up of melanoma patients , 2001, Cancer.

[20]  E. Thiel,et al.  Nested quantitative real time PCR for detection of occult tumor cells. , 2001, Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer.

[21]  W. Sterry,et al.  Ultrasound‐guided fine‐needle aspiration cytology in the early detection of melanoma metastases , 2000, Cancer.

[22]  J. Högel,et al.  Correlation of positive RT-PCR for tyrosinase in peripheral blood of malignant melanoma patients with clinical stage, survival and other risk factors , 1999, British Journal of Cancer.

[23]  A. Y. de Kanter,et al.  Multicentre study of ultrasonographically guided axillary node biopsy in patients with breast cancer , 1999, The British journal of surgery.

[24]  C. Voit,et al.  Detection of regional melanoma metastases by ultrasound B-scan, cytology or tyrosinase RT-PCR of fine-needle aspirates , 1999, British Journal of Cancer.

[25]  C. Voit,et al.  Identification of melanoma metastases by tyrosinase-reverse transcription-polymerase chain reaction of fine needle aspirates. , 1998, Journal of the American Academy of Dermatology.

[26]  M. Ross,et al.  Patterns of recurrence following a negative sentinel lymph node biopsy in 243 patients with stage I or II melanoma. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[27]  S. Burchill,et al.  Reliability of reverse transcription-polymerase chain reaction (RT-PCR)-based assays for the detection of circulating tumour cells: a quality-assurance initiative of the EORTC Melanoma Cooperative Group. , 1998, European journal of cancer.

[28]  D. Coit,et al.  Prognostic significance of peripheral blood and bone marrow tyrosinase messenger RNA in malignant melanoma. , 1998, Clinical cancer research : an official journal of the American Association for Cancer Research.

[29]  Theo Wiggers,et al.  Ultrasound-Guided Aspiration Biopsy for Detection of Nonpalpable Axillary Node Metastases in Breast Cancer Patients: New Diagnostic Method , 1997, World Journal of Surgery.

[30]  M. Lise,et al.  The impact of ultrasound scanning in the staging and follow-up of patients with clinical stage I cutaneous melanoma. , 1997, European journal of cancer.

[31]  D. Garrison,et al.  Detection of occult melanoma cells in blood with a multiple-marker polymerase chain reaction assay. , 1995, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[32]  K. Pittman,et al.  Detection of melanoma cells in peripheral blood by means of reverse transcriptase and polymerase chain reaction , 1991, The Lancet.

[33]  J. Lawless Statistical Models and Methods for Lifetime Data , 1983 .