BRAF and NRAS prognostic values in conjunctival melanoma: analysis and literature review

Arq Bras Oftalmol. 2023 Oct 13;86(5):e20230071. doi: 10.5935/0004-2749.20230071. eCollection 2023.

Abstract

Purpose: Conjunctival melanoma is a rare and aggressive tumor with a propensity for regional and distant metastases. This study aimed to analyze BRAF/NRAS markers in conjunctival melanoma and their relationship with tumor recurrences and patient prognosis.

Methods: This retrospective, observational, single-center study included consecutive patients with an anatomopathological diagnosis of conjunctival melanoma, registered between January 1992 and December 2019. BRAF/NRAS mutations were analyzed using cobas®4800 kit (Roche®) in samples obtained by excisional or map biopsy. Additionally, the presence of other associated precancerous or tumor lesions was assessed.

Results: A total of 12 patients with positive histological samples for conjunctival melanoma were included (7 women, 5 men), with a mean age at diagnosis of 60 years and a mean evolution time of 6.38 ± 3.4 years. BRAF V600E mutation was observed in three biopsies (25%), similar to NRAS Q61X (25%). Recurrences occurred in all patients with positive BRAF or NRAS mutation, and five of these patients developed systemic dissemination (83.33%). Moreover, four of six patients with mutated BRAF or NRAS (66.66%) had histopathological findings of tumor or precancerous lesions.

Conclusions: BRAF and NRAS mutations may be risk factors for recurrence and shorter survival in conjunctival melanoma, which would make these patients candidates for targeted therapies and comprehensive and individualized follow-up. All these data warrant standardized prospective studies.

MeSH terms

  • Bone Neoplasms*
  • Conjunctival Neoplasms* / genetics
  • Conjunctival Neoplasms* / pathology
  • Female
  • GTP Phosphohydrolases / genetics
  • Humans
  • Male
  • Melanoma* / genetics
  • Melanoma* / pathology
  • Membrane Proteins / genetics
  • Mutation
  • Neoplasm Recurrence, Local / genetics
  • Observational Studies as Topic
  • Prognosis
  • Prospective Studies
  • Proto-Oncogene Proteins B-raf / genetics
  • Retrospective Studies
  • Skin Neoplasms* / pathology

Substances

  • BRAF protein, human
  • GTP Phosphohydrolases
  • Membrane Proteins
  • NRAS protein, human
  • Proto-Oncogene Proteins B-raf