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

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

Francisco Javier Valentín-Bravo  1 , Álvaro Pérez-Rodríguez  2 , Ciro García-Álvarez  1 , Elena García-Lagarto  3 , María Antonia Saornil-Álvarez  1
Affiliations

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

Francisco Javier Valentín-Bravo et al. Arq Bras Oftalmol. .

Abstract
in English, Portuguese

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.

Objetivo: O melanoma da conjuntiva é um tumor raro e agressivo, com propensão à disseminação metastática regional e distante. Este estudo tem como objetivo analisar os marcadores BRAF e NRAS no melanoma da conjuntiva e sua relação com recidivas tumorais e com o prognóstico do paciente.

Métodos: Este foi um estudo retrospectivo, observacional e unicêntrico de pacientes consecutivos com diagnóstico anatomopatológico de melanoma da conjuntiva feito entre janeiro de 1992 e dezembro de 2019. As mutações BRAF e NRAS foram analisadas com o kit cobas® 4800 (Roche®) em amostras obtidas através de biópsia excisional ou por mapa. Além disso, foi avaliada a presença de lesões pré-cancerosas ou tumorais associadas.

Resultados: Foram incluídos 12 pacientes com amostras histológicas positivas para melanoma da conjuntiva (7 mulheres e 5 homens), com idade média ao diagnóstico de 60 anos e tempo médio de evolução de 6,38 ± 3,4 anos. A mutação BRAF V600E foi encontrada em 3 biópsias (25%), bem como a NRAS Q61X (25%). Ocorreram recidivas em todos os pacientes positivos para mutações de BRAF ou NRAS e 5 desses pacientes desenvolveram disseminação sistêmica (83,33%). Além disso, 4 dos 6 pacientes com BRAF ou NRAS mutante (66,66%) apresentaram achados histopatológicos de lesões tumorais ou pré-cancerosas. Conclusões: As mutações BRAF e NRAS podem ser fatores de risco para recorrência e menor sobrevida no melanoma da conjuntiva, o que tornaria esses pacientes candidatos a terapias direcionadas e a um acompanhamento mais abrangente e individualizado. Todos esses dados justificam mais estudos prospectivos padronizados.

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Conflict of interest statement

Disclosure of potential conflicts of interest: None of the authors have any potential conflicts of interest to disclose.

Figures

Figure 1
Figure 1
Clinical image of amelanotic conjunctival melanoma.
Figure 2
Figure 2
(A) Hematoxylin and eosin ×4/×40: The tumor consisted of epithelioid cells with atypical nuclei and eosinophilic cytoplasm. A neoplastic proliferation of melanocytic lineage consisting of epithelioid cells with atypical nuclei and multiple mitotic figures is observed. (B) Melan A ×4/×40: The tumor cells showed intense and diffuse cytoplasmic expression for Melan A, confirming its melanic origin.
See this image and copyright information in PMC

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