title: Molecular alterations in clinical stage III cutaneous melanoma: Correlation with clinicopathological features and patient outcome.
abstract: The aim of the present study was to evaluate the frequency and type of oncogenic v-raf murine sarcoma viral oncogene homolog B1 (BRAF)/neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS)mutations in cutaneous melanoma with clinically detected nodal metastases (stage IIIB and C) in relation to clinicopathological features and outcome. The clinicopathological data of 250 patients following therapeutic lymphadenectomy (LND) between 1995 and 2010, as well asBRAF/NRASmutational status in corresponding nodal metastases, were analyzed. The median follow-up time was 53 months.BRAFmutations were detected in 154 (62%) cases (141 p.V600E, nine p.V600K and four others) and mutually exclusiveNRASmutations were detected in 42 (17%) cases. The presence of aBRAFmutation was found to correlate with patients of a younger age. The five-year overall survival (OS) rate was 33 and 43% for LND and primary tumor excision, respectively, and the five-year disease-free survival (DFS) rate for LND was 25%. No correlation was identified betweenBRAF/NRASmutational status and RFS or OS (calculated from the date of the LND and primary tumor excision); forBRAF- andNRAS-mutated melanoma, the prognosis was the same for patients with wild-type (WT) melanoma. The important factors which had a negative impact on OS and DFS were as follows: Male gender, >1 metastatic lymph node and extracapsular extension of nodal metastases. The interval between the diagnosis of the initial melanoma to regional nodal metastasis (median, 10 months) was not significantly different betweenBRAF-mutant and -WT patients. Our largest comprehensive molecular analysis of clinical stage III melanoma revealed thatBRAFandNRASmutational status is not a prognostic marker in stage III melanoma patients with macroscopic nodal involvement, but may have implications for potential adjuvant therapy.
authors: Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw 02-781, Poland.
authors: Piotr
authors: P
authors: Rutkowski
authors: Department of Molecular Biology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw 02-781, Poland.
authors: Aleksandra
authors: A
authors: Gos
authors: Department of Biochemistry and Molecular Biology, Institute of Rheumatology, Warsaw 02-637, Poland.
authors: Monika
authors: M
authors: Jurkowska
authors: Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw 02-781, Poland.
authors: Tomasz
authors: T
authors: Switaj
authors: Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw 02-781, Poland.
authors: Wirginiusz
authors: W
authors: Dziewirski
authors: Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw 02-781, Poland.
authors: Marcin
authors: M
authors: Zdzienicki
authors: Department of Pathology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw 02-781, Poland ; Department of Pathology, Center of Postgraduate Medical Education, Warsaw 01-809, Poland.
authors: Konrad
authors: K
authors: Ptaszyński
authors: Department of Pathology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw 02-781, Poland.
authors: Wanda
authors: W
authors: Michej
authors: Department of Molecular Biology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw 02-781, Poland.
authors: Andrzej
authors: A
authors: Tysarowski
authors: Department of Molecular Biology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw 02-781, Poland.
authors: Janusz A
authors: JA
authors: Siedlecki
keywords: lymph node; melanoma; metastases; molecular factors; neuroblastoma RAS viral (v-ras) oncogene homolog; v-raf murine sarcoma viral oncogene homolog B1