Immunohistochemical and molecular profiling of uveal melanoma: clinicopathological correlations from an Italian cohort.
Most uveal melanomas carry a GNAQ or GNA11 gene mutation
Immunohistochemical and molecular profiling of uveal melanoma: clinicopathological correlations from an Italian cohort.
Uveal melanoma (uveal melanoma) is the most common primary intraocular malignancy in adults, characterized by distinct histopathological and molecular features and often associated with poor prognosis due to its high metastatic potential.
We retrospectively analyzed 84 uveal melanoma cases from a single institution using an integrated approach combining histological classification, immunohistochemical profiling, and targeted next-generation sequencing with a 63-gene panel.
Loss of BAP1 expression correlated with epithelioid histology and denser T-cell infiltration yet lacked PD-L1 expression.
Aberrant p53 staining was more frequent in spindle-cell tumors, though TP53 mutations were rare, suggesting functional inactivation through other mechanisms.
Notably, mutations typically associated with cutaneous melanomas (e.g., BRAF , KIT , CDKN2A ) were also detected, particularly in a single iris melanoma, suggesting site-specific molecular convergence.
Additional recurrent alterations were found in NOTCH1 , PTEN , PIK3CA , and KDR , implicating the mTOR and VEGF signaling pathways.
This study highlights the heterogeneous molecular landscape of uveal melanoma and underscores the importance of integrating histopathological and molecular data for improved prognostic stratification.
The identification of potential therapeutic targets and atypical mutations typically associated with other melanoma subtypes suggests avenues for future research and tailored therapeutic strategies.