Molecular Characterization and Patient Outcome of Melanoma Nodal Metastases and an Unknown Primary Site

Aleksandra Gos, Monika Jurkowska, Alexander van Akkooi, Caroline Robert, Hanna Kosela-Paterczyk, Senada Koljenović, Nyam Kamsukom, Wanda Michej, Arkadiusz Jeziorski, Piotr Pluta, Cornelis Verhoef, Janusz A. Siedlecki, Alexander M.M. Eggermont, Piotr Rutkowski

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

25 Citaten (Scopus)

Samenvatting

Background: Melanoma of unknown primary site (MUP) is not a completely understood entity with nodal metastases as the most common first clinical manifestation. The aim of this multicentric study was to assess frequency and type of oncogenic BRAF/NRAS/KIT mutations in MUP with clinically detected nodal metastases in relation to clinicopathologic features and outcome.

Materials and Methods: We analyzed series of 103 MUP patients (period: 1992–2010) after therapeutic lymphadenectomy (LND): 40 axillary, 47 groin, 16 cervical, none treated with BRAF inhibitors. We performed molecular characterization of BRAF/NRAS/KIT mutational status in nodal metastases using direct sequencing of respective coding sequences. Median follow-up time was 53 months.

Results: BRAF mutations were detected in 55 cases (53 %) (51 V600E, 93 %; 4 others, 7 %), and mutually exclusive NRAS mutations were found in 14 cases (14 %) (7 p.Q61R, 4 p.Q61K, 2 p.Q61H, 1 p.Q13R). We have not detected any mutations in KIT. The 5-year overall survival (OS) was 34 %; median was 24 months. We have not found significant correlation between mutational status (BRAF/NRAS) and OS; however, for BRAF or NRAS mutated melanomas we observed significantly shorter disease-free survival (DFS) when compared with wild-type melanoma patients (p = .04; 5-year DFS, 18 vs 19 vs 31 %, respectively). The most important factor influencing OS was number of metastatic lymph nodes >1 (p = .03).

Conclusions: Our large study on molecular characterization of MUP with nodal metastases showed that MUPs had molecular features similar to sporadic non-chronic-sun-damaged melanomas. BRAF/NRAS mutational status had negative impact on DFS in this group of patients. These observations might have potential implication for molecular-targeted therapy in MUPs.

Originele taal-2Engels
Pagina's (van-tot)4317-4323
Aantal pagina's7
TijdschriftAnnals of Surgical Oncology
Volume21
Nummer van het tijdschrift13
DOI's
StatusGepubliceerd - 31 okt. 2014
Extern gepubliceerdJa

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