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Purpose As activating mutations of BRAF and NRAS have been identified in 47% of conjunctival melanoma, we evaluated the activation status of the MAP kinase and PI3K/mTOR pathways in benign and malignant conjunctival melanocytic proliferations. As loss of PTEN locus has been reported in conjunctival melanoma, we also assessed the expression of PTEN in conjunctival nevi and melanoma. Methods The phosphorylation status of MEK, ERK, AKT, S6 ribosomal protein and the expression of PTEN was evaluated by immunohistochemistry in 35 conjunctival naevi and 31 conjunctival melanoma. Statistical analysis was performed with JUMP 8,0 software. Immunohistochemistry was assessed independently by three observers. Results There were 13 subepithelial nevi and 22 compound nevi. There were 14 females and 21 males with a mean age was 36.9 yo. P-MEK, p-ERK, p-S6, p-AKT and PTEN were respectively found in 59%, 49 %, 49%, 83.9% and 100% of the nevi. The melanoma group was composed of 17 females and 14 males with a mean age of 67.1 yo. P-MEK, p-ERK, p-AKT, p-S6 and PTEN were respectively found in 87%, 87%, 94.3%, 94% and 96.7% of the melanoma. The phosphorylation of MEK and ERK, AKT and S6 was significantly elevated in the melanoma compared to the nevi (p=0,0050; p=0,0004; p=0,0031;p> 0,0001 respectively). There was also a significant correlation between the activation of MEK and ERK (p=0,0045). Conclusion Our results demonstrate ex vivo a significant increase in the activation of the MAP kinase pathway in malignant conjunctival melanocytic proliferations as well as a significant increase in the phosphorylation of pAKT and S6 ribosomal protein, suggesting a contribution of the PI3K/mTOR pathway to conjunctival melanoma development. |
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