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

Abstract

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.

Dermokine mutations contribute to epithelial-mesenchymal transition and advanced melanoma through ERK/MAPK pathways

“…The present study observed an association between high DMKN levels with tumor invasion and a higher incidence of BRAFV600E and NRASP29S mutation metastasis. The BRAFV600E and NRASP29S hotspots are detectable in more than 80% of the melanoma samples and can induce various physiological functions in response to chemo- and immunotherapy [ 76 , 77 ]. Furthermore, Melan-A and Ki67 are considered invasive immunohistochemical markers with 100% sensitivity and specificity in distinguishing melanoma from non-melanocytic cancers [ 11 , 78 ].…”

Development and validation of a nomogram to predict overall survival of conjunctival melanoma: a population-based study

“…Molecular biological research is an important field for the treatment of CM at present ( 24 - 27 ). There have been studies to detect the genetic characteristics of CM patients, and frequent mutations in BRAF (46.7%, 7/15), NRAS (26.7%, 4/15), NF1 (20%, 3/15) and TERT promoter (46.7%, 7/15) have been found in CM patients ( 28 , 29 ), It is also found that targeted therapy (TT) (BRAF ± MEK inhibitor) ( 30 , 31 ) or immune checkpoint inhibitor (ICI) [anti-programmed cell death protein 1 (PD-1) ± anti-cytotoxic T-lymphocyte associated protein 4 (CTLA4)] can improve the survival of patients with advanced CM ( 28 , 32 ). However, we have not obtained such data from the SEER database.…”

Dermokine mutations contribute to epithelial-mesenchymal transition and advanced melanoma through ERK/MAPK pathways

“…Regarding the present study, an association was observed between high DMKN levels with tumor invasion, as well as a higher incidence of BRAFV600E and NRASP29S mutation metastasis. The BRAFV600E and NRASP29S hotspots are detectable in more than 80% of the melanoma samples and can induce various physiological functions in response to chemo-and immunotherapy [42,43]. Furthermore, Melan-A and Ki67 are considered invasive immunohistochemical markers with 100% sensitivity and speci city in distinguishing melanoma from non-melanocytic cancers [11,44].…”