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

## 研究目的
结膜黑色素瘤是一种罕见且具有侵袭性的肿瘤，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。

## 研究方法
本研究为回顾性、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、经组织病理学诊断为结膜黑色素瘤的连续入组患者。采用罗氏（Roche®）cobas®4800检测试剂盒，对切除活检或地图活检获取的样本进行BRAF/NRAS突变分析。此外，本研究还评估了其他相关癌前病变或肿瘤性病变的存在情况。

## 研究结果
本研究共纳入12例经组织学证实为结膜黑色素瘤的患者（7例女性，5例男性），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%），检出比例与NRAS Q61X突变（25%）相近。BRAF或NRAS突变阳性的患者均出现了肿瘤复发，其中5例患者发生了全身播散（占比83.33%）。此外，6例携带BRAF或NRAS突变的患者中，有4例（66.66%）存在肿瘤或癌前病变的组织病理学表现。

## 研究结论
BRAF与NRAS突变可能是结膜黑色素瘤患者出现肿瘤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及全面个体化的随访监测。上述所有研究结果均需开展标准化的前瞻性研究予以验证。