Validation of a clinicopathological and gene expression profile model for sentinel lymph node metastasis in primary cutaneous melanoma

E E A P Mulder, J T Dwarkasing, D Tempel, A van der Spek, L Bosman, D Verver, A L Mooyaart, A A M van der Veldt, C Verhoef, T E C Nijsten, D J Grunhagen, L M Hollestein*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Background
The Clinicopathological and Gene Expression Profile (CP-GEP) model was developed to accurately identify patients with T1–T3 primary cutaneous melanoma at low risk for nodal metastasis.

Objectives
To validate the CP-GEP model in an independent Dutch cohort of patients with melanoma.

Methods
Patients (aged ≥ 18 years) with primary cutaneous melanoma who underwent sentinel lymph node biopsy (SLNB) between 2007 and 2017 at the Erasmus Medical Centre Cancer Institute were eligible. The CP-GEP model combines clinicopathological features (age and Breslow thickness) with the expression of eight target genes involved in melanoma metastasis (ITGB3, PLAT, SERPINE2, GDF15, TGFBR1, LOXL4, CXCL8 and MLANA). Using the pathology result of SLNB as the gold standard, performance measures of the CP-GEP model were calculated, resulting in CP-GEP high risk or low risk for nodal metastasis.

Results
In total, 210 patients were included in the study. Most patients presented with T2 (n = 94, 45%) or T3 (n = 70, 33%) melanoma. Of all patients, 27% (n = 56) had a positive SLNB, with nodal metastasis in 0%, 30%, 54% and 16% of patients with T1, T2, T3 and T4 melanoma, respectively. Overall, the CP-GEP model had a negative predictive value (NPV) of 90·5% [95% confidence interval (CI) 77·9–96.2], with an NPV of 100% (95% CI 72·2–100) in T1, 89·3% (95% CI 72·8–96·3) in T2 and 75·0% (95% CI 30·1–95·4) in T3 melanomas. The CP-GEP indicated high risk in all T4 melanomas.

Conclusions
The CP-GEP model is a noninvasive and validated tool that accurately identified patients with primary cutaneous melanoma at low risk for nodal metastasis. In this validation cohort, the CP-GEP model has shown the potential to reduce SLNB procedures in patients with melanoma.
Original languageEnglish
Pages (from-to)944-951
Number of pages8
JournalBritish Journal of Dermatology
Volume184
Issue number5
Early online date26 Aug 2020
DOIs
Publication statusPublished - May 2021

Bibliographical note

Funding Information: This work was supported by the National Enterprising Netherlands Agency.

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