TY - JOUR
T1 - Molecular Characterization and Patient Outcome of Melanoma Nodal Metastases and an Unknown Primary Site
AU - Gos, Aleksandra
AU - Jurkowska, Monika
AU - van Akkooi, Alexander
AU - Robert, Caroline
AU - Kosela-Paterczyk, Hanna
AU - Koljenović, Senada
AU - Kamsukom, Nyam
AU - Michej, Wanda
AU - Jeziorski, Arkadiusz
AU - Pluta, Piotr
AU - Verhoef, Cornelis
AU - Siedlecki, Janusz A.
AU - Eggermont, Alexander M.M.
AU - Rutkowski, Piotr
N1 - Publisher Copyright:
© 2014, The Author(s).
PY - 2014/10/31
Y1 - 2014/10/31
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84911957919&partnerID=8YFLogxK
U2 - 10.1245/s10434-014-3799-y
DO - 10.1245/s10434-014-3799-y
M3 - Article
C2 - 24866436
AN - SCOPUS:84911957919
SN - 1068-9265
VL - 21
SP - 4317
EP - 4323
JO - Annals of Surgical Oncology
JF - Annals of Surgical Oncology
IS - 13
ER -