1005P - Molecular analysis in serial biopsies in sinonasal mucosal melanoma

Date 09 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Skin cancers
Translational Research
Melanoma
Basic Principles in the Management and Treatment (of cancer)
Presenter Georgia Anguera Palacios
Citation Annals of Oncology (2016) 27 (6): 328-350. 10.1093/annonc/mdw376
Authors G. Anguera Palacios1, M.Á. Molina-Vila2, J.R. Gras-Cabrerizo3, X. León3, C. Mayo2, J. Codony Servat2, A. Pérez-Rosado2, S. Rodríguez2, M. González-Cao4, N. Karachaliou4, A. Barnadas1, R. Rosell4, M. Majem1
  • 1Medical Oncology, Hospital de la Santa Creu i Sant Pau, 08026 - Barcelona/ES
  • 2Laboratory Of Cellular And Molecular Biology, Pangaea Biotech SL, IOR Quirón-Dexeus University Institute, 08028 - Barcelona/ES
  • 3Otolaryngology/head And Neck Surgery, Hospital de la Santa Creu i Sant Pau, 08026 - Barcelona/ES
  • 4Medical Oncology Service, Instituto Oncológico Dr Rosell (IOR), Hospital Universitario Quirón-Dexeus, 08028 - Barcelona/ES

Abstract

Background

Melanomas from the mucosal surface are a rare entity, of which approximately 25% arise from the nasosinusal region. Given the low incidence of this entity, it is not well known the incidence of genetic alterations in sinonasal mucosal melanomas (SMM). The purpose of this study is to analyse mutational status of patients (pts) with SMM in primary tumors and in locoregional and/or distant relapse.

Methods

From 1988 to 2015, 25 pts were diagnosed of SMM in our institution. We collected formalin-fixed paraffin blocks from 19 primary tumors and, in 12 of them, from local recurrence and/or distant metastasis. Median number of samples per patient was 3 (range 1-9). We analysed the spectrum of mutations in KIT gene (exon 9, 11 13 and 17) by standard PCR followed by Sanger sequencing, NRAS gene (exon 2, 3 and 4) by pyrosequencing and BRAF gene (exon 15) by Taqman PCR.

Results

The median age at diagnosis was 75 (range 42-86), 13 were males and 12 females. According to the TNM-SMM system, the pts were classified as T3 in 12 cases (48%), as T4a in 5 cases (20%), and 8 pts (32%) as T4b. 23/25 pts underwent surgery followed by radiotherapy, if needed, as first treatment and 2 pts received palliative chemotherapy with a DTIC-based schedule. 9/25 pts (36%) presented locoregional recurrence (36%) and 8 of 25 pts (32%) develop distant metastasis. We performed molecular analysis in 19 cases and we identified gene mutations in 5 cases, all from the nasal cavity. We found 2 cases (10.5%) with mutations in NRAS gene (both in exon 2: G12V) and 3 cases (15.8%) with mutations in KIT (all in the exon 11: R586K, G565R, M552I). No BRAF mutations were detected. Interestingly, we found discrepancies in the NRAS mutational status of tumor samples obtained from 2 pts. In the first case, at diagnosis, we identified the NRAS mutation in 1 of 2 samples, and in 2 of 3 samples at the time of local recurrence. In the second case, the NRAS mutation was present at diagnosis but only in 2 of 4 samples of distant recurrence.

Conclusions

In our series of SMM, we have found a KIT mutation rate of 15,8% and a 10.5% in NRAS mutation. No BRAF mutations were detected. We have observed differences in mutation status between different tumor samples in 2 pts with NRAS mutations that might be explained by tumor heterogeneity.

Clinical trial identification

Legal entity responsible for the study

Hospital de la Santa Creu i Sant Pau and Laboratory on Oncology/Pangaea Biotech

Funding

Hospital de la Santa Creu i Sant Pau and Laboratory on Oncology/Pangaea Biotech

Disclosure

All authors have declared no conflicts of interest.