SOX10 Expression as Well as BRAF and GNAQ/11 Mutations Distinguish Pigmented Ciliary Epithelium Neoplasms From Uveal Melanomas.

Purpose: Adenocarcinomas or adenomas derived from pigmented ciliary epithelium (APCE) are exceptionally rare ocular tumors. These tumors have pigmented and epithelioid features, and some APCEs are negative for keratin markers and positive for melanocytic markers. It is especially difficult to distinguish APCEs from uveal melanoma (UM). Accordingly, we examined protein expression and genetic mutations associated with APCE to facilitate diagnosis.

Methods: Five APCE and 11 UM samples were obtained from patients during surgical resection at our institute. APCE and UM ocular structures were compared comprehensively. Protein expression and genetic alterations involved in malignant melanoma were evaluated.

Results: SOX10 was expressed diffusely in all 11 UMs and in surrounding uveal or choroidal melanocytes, but not in the APCEs or nontumorous pigmented epithelia. Additionally, the expression patterns of cytokeratins and melanocytic markers differed between UMs and APCEs. We identified BRAF V600E mutations in four of five APCE samples, but not in the 11 UM samples. Moreover, GNAQ or GNA11 mutations were found in 10 of the 11 UM samples, but not in APCE samples. NRAS mutations were not observed in either tumor group examined.

Conclusions: APCE is a separate entity distinguished from UM by the absence of SOX10 expression and presence of the BRAF V600E mutation. These results have implications for diagnosis, providing a means to distinguish between UM and APCE.