Prognostic Factor Utility of BAP1 Immunohistochemistry in Uveal Melanoma: A Single Center Study in Spain

SIMPLE SUMMARY: As uveal melanoma metastasis rates are still very high, the mechanisms by which it spreads need to be evaluated. Our research sought to determine which pathological and clinical features were correlated with the prognosis of uveal melanoma in a Spanish community. BAP1 (BRCA1-Associated Protein 1) gene mutation is one of the strongest predictors for metastasis in uveal melanoma. The BAP1 protein has a tumor suppressor function and the presence of the BAP1 protein can be shown using immunohistochemical staining. Our study showed that nuclear BAP1 immunostaining had a significant correlation with survival rate in our sample, and patients with a lack of nuclear BAP1 immunostaining should be considered high-risk and receive a close follow-up. This stain can be used as routine technique in the pathological examination of uveal melanoma. ABSTRACT: Even today, the mortality rate for uveal melanoma (UM) remains very high. In our research, we sought to determine which pathological and clinical features were correlated with the prognosis of UM. BAP1 (BRCA1-Associated Protein 1) gene mutation has been analyzed as one of the strongest predictors for metastasis in UM. The BAP1 gene codifies the BAP1 protein which has a tumor suppressor function. The presence of this protein can be determined by BAP1 immunohistochemical staining. Eighty-four uveal melanoma patients and forty enucleated eyeballs were examined. Metastasis was present in 24 patients. Nuclear BAP1 staining was low in 23 patients. The presence of a higher large basal diameter tumor (p < 0.001), tumor infiltrating lymphocytes (p = 0.020), and a lack of nuclear BAP1 immunostaining (p = 0.001) ocurred significantly more often in the metastatic group. Metastasis-free survival was lower in patients with low nuclear BAP1 staining (p = 0.003). In conclusion, to the best of our knowledge, this is the first time that BAP1 staining has been studied in uveal melanoma in a Spanish community. We believe that this technique should become routine in the pathological examination of uveal melanoma in order to allow adequate classification of patients and to establish an individual follow-up plan.