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

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.

摘要 目的：结膜黑色素瘤（conjunctival melanoma）是一种罕见且极具侵袭性的肿瘤，易发生区域及远处转移。本研究旨在分析结膜黑色素瘤中的BRAF/NRAS标志物，及其与肿瘤复发和患者预后的关联。方法：本项回顾性、观察性单中心研究纳入了1992年1月至2019年12月期间登记的、经病理组织学确诊为结膜黑色素瘤的连续入组患者。采用cobas®4800检测试剂盒（罗氏®）对切除活检或多点活检获取的样本进行BRAF/NRAS突变检测。此外，本研究还评估了其他相关癌前病变或肿瘤病变的存在情况。结果：共计纳入12例结膜黑色素瘤组织学检测阳性的患者（女性7例，男性5例），诊断时平均年龄为60岁，平均病程为6.38±3.4年。3例活检样本检出BRAF V600E突变（占比25%），NRAS Q61X突变检出率同样为25%。所有携带BRAF或NRAS突变的患者均出现肿瘤复发，其中5例患者发生全身转移（占比83.33%）。此外，6例携带BRAF或NRAS突变的患者中，有4例存在肿瘤或癌前病变的病理组织学表现（占比66.66%）。结论：BRAF与NRAS突变可能是结膜黑色素瘤患者复发及生存期缩短的危险因素，这提示此类患者可考虑接受靶向治疗，并进行全面个体化的随访监测。上述研究结果亟需开展标准化的前瞻性研究予以验证。