Abstract
Simple SummarySentinel lymph node (SLN) status is still the most important prognostic factor for melanoma patients; however, the efficacy of completing lymph node dissection remains questionable. The aim of our study was to assess the correlation between known prognostic factors, mutational occurrence of BRAF and NRAS in the primary tumor, and SLN status. Statistical analysis revealed that Breslow thickness was associated with SLN status; however, neither NRAS nor BRAF showed a predictive value. Furthermore, NRAS mutation in primary tumors proved to be an independent factor of tumor progression. This suggests that regardless of the SLN status, the NRAS-mutant subgroup of patients requires closer monitoring.Purpose: To assess the prognostic role of sentinel lymph node status (SLN) in melanoma patients, a statistical comparison was performed with the application of already known prognostic factors, mutational occurrence of BRAF and NRAS in the primary tumor, as well as disease outcome. Methods: Our retrospective single-center study involved 159 melanoma cases, who underwent SLN biopsy. The following clinico-pathological data were collected: age, gender, location of primary tumor, Breslow thickness, ulceration degree, histological subtype, mitosis count, lymphovascular and perineural invasion, presence of tumor-infiltrating lymphocytes, regression signs, mutations of BRAF and NRAS of the primary tumors, and SLN status. Results: From the studied clinico-pathological factors, only Breslow thickness increased the risk of SLN positivity (p = 0.025) by multivariate analysis, while neither BRAF nor NRAS mutation of the primary tumor proved to be a predictor of the SLN status. While the NRAS-mutant subgroup showed the most unfavorable outcome for progression-free and distant metastasis-free survival, their rate of positive SLNs proved to be relatively lower than that of patient groups with BRAF mutation and double-wild-type phenotypes. Conclusion: Similarly to the importance of SLN positivity, NRAS mutation of the primary tumor proved to be an independent prognostic factor of progression. Therefore, despite negative SLN, this NRAS-mutant subgroup of patients still requires closer monitoring to detect disease progression.
Highlights
The incidence of melanoma shows a continuous increase worldwide
The aim of our study was to assess the correlation between known prognostic factors of melanoma, mutational occurrence of BRAF and NRAS in the primary tumor, and sentinel lymph node status
Primary melanomas were removed in two steps; a 5 mm safety margin was completed to 1–2 cm according to the WHO guideline sentinel lymph node (SLN) biopsy was performed in the following cases: intermediate tumor thickness (1–4 mm), less than 1 mm if the primary tumor was ulcerated, Clark level higher than III, lymphovascular invasion, or high mitosis activity, more than 4 mm Breslow thickness if the tumors were not ulcerated
Summary
During the past few decades, the number of new cases has multiplied [1,2]. Experimental and clinical research in the last decades investigated the molecular and immunological background of melanoma and successfully established the base of novel innovative therapeutic modalities such as target-based therapies and immunotherapies and the clinical application of new prognostic and predictive factors [3,4,5]. In 90% of cases with a BRAF mutation, a valine-to-glutamic-acid mutation is present at codon 600 of exon 15 (V600E). The presence of BRAF mutation is an attractive target of melanoma therapy, its prognostic value is still elusive
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