Abstract
Background
Sentinel node (SN) biopsy is regarded as standard of care for patients (pts) with cutaneous melanoma ≥1.0 mm of thickness. In the recent AJCC classification, findings in the SN are simply classified as positive or negative. In our analyses, we were interested whether quantitative real-time PCR (qRT-PCR) is able to predict disease-free survival (DFS) and overall survival (OS) depending on tumour burden in the SN.
Methods
One hundred and forty-five pts were analysed using qRT-PCR for tyrosinase. Results were analysed using accelerated failure time survival model and cox proportional hazards models using the R statistics framework.
Results
Forty-one pts (28%) were positive according to qRT-PCR. In total, 12 of 41 pts showed tumour deposits in the SN using S100 and/or HMB-45-labelled immunohistochemistry as well. One patient had micrometastases detected by immunohistochemistry staining but failed in the qRT-PCR. After 10 years of follow-up, 34 patients recurred and 27 patients died. Significant differences for DFS and OS were detected for sex, increasing tumour thickness, ulceration of the primary tumour, and metastatic spread in the SN determined by histology as well as qRT-PCR.
Conclusion
Quantitative analyses showed a logarithmic correlation between tumour burden and prognosis. However, as multivariate analyses reveal qRT-PCR was not superior compared to classical histology or immunohistology.
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References
Balch CM et al (2009) Final version of AJCC melanoma staging and classification. J Clin Oncol 27:6199–6206. doi:10.1200/JCO.2009.23.4799
Blaheta HJ et al (2000) Examination of regional lymph nodes by sentinel node biopsy and molecular analysis provides new staging facilities in primary cutaneous melanoma. J Invest Dermatol 114:637–642. doi:10.1046/j.1523-1747.2000.00925.x
Eggermont AM et al (2008) Adjuvant therapy with pegylated interferon alfa-2b versus observation alone in resected stage III melanoma: final results of EORTC 18991, a randomised phase III trial. Lancet 372:117–126. doi:10.1016/S0140-6736(08)61033-8
Garbe C, Schadendorf D (2003) Malignes Melanom-neue Daten und Konzepte zur Nachsorge Dtsch Arztebl. International 100:1804–1808
Gloghini A, Canal B, Klein U, Dal Maso L, Perin T, Dalla-Favera R, Carbone A (2004) RT-PCR analysis of RNA extracted from Bouin-fixed and paraffin-embedded lymphoid tissues. J Mol Diagn JMD 6:290–296
Harrell Jr FE (2015) Regression modeling strategies, 2 edn. Springer, New York. doi:10.1007/978-1-4757-3462-1
Leiter U et al (2016) Complete lymph node dissection versus no dissection in patients with sentinel lymph node biopsy positive melanoma (DeCOG-SLT): a multicentre, randomised, phase 3 trial. Lancet Oncol 17:757–767. doi:10.1016/S1470-2045(16)00141-8
Morton DL et al (1992) Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg 127:392–399
Riber-Hansen R, Abrahamsen HN, Sorensen BS, Hamilton-Dutoit SJ, Steiniche T (2008) Quantitative real-time RT-PCR in sentinel lymph nodes from melanoma patients. Detection of melanocytic mRNA predicts disease-free survival. APMIS 116:199–205. doi:10.1111/j.1600-0463.2008.00960.x
Starz H, Balda BR, Kramer KU, Buchels H, Wang H (2001) A micromorphometry-based concept for routine classification of sentinel lymph node metastases and its clinical relevance for patients with melanoma. Cancer 91:2110–2121
Starz H, Haas CJ, Schulz GM, Balda BR (2003) Tyrosinase RT-PCR as a supplement to histology for detecting melanoma and nevus cells in paraffin sections of sentinel lymph nodes. Mod Pathol 16:920–929. doi:10.1097/01.MP.0000086074.55963.24
Ulmer A et al (2014) Quantitative measurement of melanoma spread in sentinel lymph nodes and survival. PLoS Med 11:e1001604. doi:10.1371/journal.pmed.1001604
van Akkooi ACJ, de Wilt JH, Verhoef C, Schmitz PI, van Geel AN, Eggermont AM, Kliffen M (2006) Clinical relevance of melanoma micrometastases (<0.1 mm) in sentinel nodes: are these nodes to be considered negative? Ann Oncol 17:1578–1585. doi:10.1093/annonc/mdl176
van Akkooi ACJ et al (2009) Excellent long-term survival of patients with minimal sentinel node tumor burden (<0.1 mm) according to Rotterdam Criteria: a study of the EORTC melanoma group. EJC Suppl 7:576–577
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Thomas Eigentler has received speaker honorarium from Novartis, Roche, MSD, BMS and AMGEN. Claus Garbe has received speaker honorarium from Novartis, Roche, MSD, BMS and AMGEN. Ulrike Leiter has received speaker honorarium from Roche. Jochen Hinderer and Seema Noor declare no conflict of interest.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.
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Eigentler, T.K., Hinderer, J., Noor, S. et al. Prognostic impact of tumour burden measured by quantitative real-time PCR from sentinel lymph nodes of melanoma patients: data from 10-year follow-up. J Cancer Res Clin Oncol 143, 703–708 (2017). https://doi.org/10.1007/s00432-016-2323-0
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DOI: https://doi.org/10.1007/s00432-016-2323-0