Specificity of tyrosinase and HMB45 PCR in the detection of melanoma metastases in sentinel lymph node biopsies

Gutzmer, Ralf; Kaspari, Markus; Brodersen, Jens P.; Mommert, Susanne; Völker, B.; Kapp, Alexander; Werfel, Thomas; Kiehl, Peter

doi:10.1046/j.1365-2559.2002.01512.x

Cited by 31 publications

(22 citation statements)

References 31 publications

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“…Molecular detection of melanoma cells within the sentinel lymph node by polymerase chain reaction (PCR) has been evaluated in various studies using different markers [198][199][200][201][202]. Especially due to its low specificity and lack of distinction between melanoma cells and melanocytic nevus cells in the sentinel lymph node [203], this method has not become established outside clinical trials.…”

Section: R Gutzmermentioning

confidence: 99%

See 1 more Smart Citation

Malignant Melanoma S3‐Guideline “Diagnosis, Therapy and Follow‐up of Melanoma”

Pflugfelder

Kochs

Blum

et al. 2013

J Deutsche Derma Gesell

181

148

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Section: R Gutzmermentioning

confidence: 99%

“…The latter are defined as cytologically inconspicuous melanocytic cells in the capsule or trabeculae of the lymph node [19,203].…”

Section: R Gutzmermentioning

confidence: 99%

Malignant Melanoma S3‐Guideline “Diagnosis, Therapy and Follow‐up of Melanoma”

Pflugfelder

Kochs

Blum

et al. 2013

J Deutsche Derma Gesell

181

148

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“…Two of their initial melanoma SLN specimens were excluded from further evaluation because nevus cells were identified by histology and immunohistochemistry. Only 8 (20.5%) of the 39 melanoma SLN that were included in the study were positive by all three evaluation methods, and another 6 (15.4%) were positive only by tyrosinase PCR [37]. These findings suggest that RT-PCR with the tyrosinase primer has a relatively low specifity.…”

Section: Rt-pcr Analysis Of Sln Using Melanocytic Markersmentioning

confidence: 88%

“…Gutzmer et al [37] have investigated the false positive rate for RT-PCR analysis of melanoma SLN by comparing the results of tyrosinase and HMB45 RT-PCR studies on SLN from melanoma patients to those obtained from lymph nodes of non-melanoma patients. They prepared multiple sections from SLN for H&E staining and for immunohistochemistry using antibodies to HMB45 and MART1.…”

Section: Rt-pcr Analysis Of Sln Using Melanocytic Markersmentioning

confidence: 99%

Pathologic analysis of sentinel lymph nodes in melanoma patients: Current and future trends

Roberts

Cochran

2004

Journal of Surgical Oncology

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Sentinel lymph node dissection (SLND) has become the standard of care for the staging of clinically-node negative melanomas and breast cancers. A large literature documents the efficacy of SLND in the staging of melanoma and breast cancer. The SLND has lower associated patient morbidity in comparison to elective node dissections that remove the closest regional-draining node group. SLND has improved accuracy over traditional regional node dissection for the staging of melanoma. Currently, several multicenter trials are evaluating the prognostic significance of melanoma micrometastases in SLN detected by immunohistochemical and molecular methods. Pending trial outcome analysis, SLND has no proven effect on mortality. However, given the current oncologic emphasis on detection and removal of nodal tumor metastases, the technique has an important role in minimizing the invasiveness of tumor staging for melanoma and breast cancer. As long as lymph node metastases are used for staging solid malignancies, surgical pathologists are likely to encounter SLN excisional biopsies as a part of their routine practice.

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“…The present large study of 220 SNs from 95 patients confirms this technique to be both convenient and reliable in use. Previous RT-PCR-based molecular studies of melanoma SNs have most often used tyrosinase mRNA as a target marker for detecting melanoma cells (12,15,17,25), the percentage of patients with positive SNs varying from 33% (26) to 88% (14). Although fewer studies have investigated the expression of MART-1 mRNA in melanoma SNs (13, 14, 27 -29), these have found a similar wide variation in expression, with positive cases ranging from 24% (14) to 81% (28).…”

Section: Discussionmentioning

confidence: 99%

Pathologic Assessment of Melanoma Sentinel Nodes: A Role for Molecular Analysis Using Quantitative Real-Time Reverse Transcription-PCR for MART-1 and Tyrosinase Messenger RNA

Abrahamsen

Sørensen²,

Nexø³

et al. 2005

Clinical Cancer Research

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Purpose: Molecular analysis of melanoma sentinel nodes (SN) is sensitive, but poorly specific because metastases cannot be distinguished from benign nevus inclusions (BNI). We investigated whether quantitative reverse transcription-PCR (RT-PCR) detection of MART-1 and tyrosinase mRNAs could improve this specificity and contribute to SN assessment.Experimental Design: Two hundred twenty SNs from 95 melanoma patients analyzed by extensive immunohistopathology and real-time quantitative RT-PCR.Results: Using histopathology, SNs and patients were allotted to three diagnostic groups: (a) metastasis positive, (b) BNI positive, and (c) melanocyte-free. Median MART-1 and tyrosinase mRNA levels in SNs were significantly different in patients with metastasis compared with patients with BNIs (P < 0.05) and patients without melanocytic lesions (P < 0.001). However, a ''gray-zone'' was observed where distinction, based on mRNA levels, could not be made between the three groups. For both genes, the highest mRNA level recorded in each RT-PCR-positive patient was positively correlated with Breslow's tumor thickness. For SNs with metastases, tumor burden was significantly correlated to the mRNA level. Using the presence of a MART-1 RT-PCR signal to detect patients with metastases, a sensitivity of 100% and a negative predictive value of 100% were achieved when extensive immunohistology was used as reference.Conclusions: Quantitative RT-PCR MART-1 and tyrosinase mRNA analysis cannot be used alone for SN diagnosis because of its poor specificity for melanoma metastasis. However, in approximately one third of cases without RT-PCR evidence of MART-1 expression, extensive histopathologic SN investigation is not necessary, thus substantially reducing the cost of SN analysis. The level of melanocyte-associated mRNA is associated with both tumor thickness and tumor burden as measured histopathologically, suggesting that this may be of prognostic value.

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Specificity of tyrosinase and HMB45 PCR in the detection of melanoma metastases in sentinel lymph node biopsies

Abstract: The specificity of tyrosinase PCR and the sensitivity of HMB45 PCR are too low to recommend these PCR examinations for the guidance of therapy, in particular complete regional lymph node dissection.

Cited by 31 publications

References 31 publications

Malignant Melanoma S3‐Guideline “Diagnosis, Therapy and Follow‐up of Melanoma”

Malignant Melanoma S3‐Guideline “Diagnosis, Therapy and Follow‐up of Melanoma”

Pathologic analysis of sentinel lymph nodes in melanoma patients: Current and future trends

Pathologic Assessment of Melanoma Sentinel Nodes: A Role for Molecular Analysis Using Quantitative Real-Time Reverse Transcription-PCR for MART-1 and Tyrosinase Messenger RNA

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