Abstract
Purpose :
BAP1 immunohistochemical (IHC) stain has emerged as a powerful and inexpensive prognostic tool in uveal melanoma (UM), correlating with UM molecular genetics and patient outcome. We aim to assess BAP1 IHC in irradiated UM eyes that ultimately underwent enucleation and to compare performance of BAP1 IHC with non-irradiated UM.
Methods :
The medical records of all UM patients who underwent enucleation at the Oncology Service of Wills Eye Hospital from December 1st, 2007 to December 31st, 2014 with available paraffin-embedded tissue and either chromosome 3 (ch3) status or sufficient follow-up (>5 years or development of metastasis) were reviewed. Nuclear BAP1 (nBAP1) IHC was interpreted as intact (positive in >90% of nuclei), lost (positive in <5% of nuclei), or heterogeneous (positive in 5-90% of nuclei). Retina, intratumoral inflammatory cells, and blood vessels served as internal positive controls. Eyes without sufficient internal positive controls or with <5% viable tumor were labeled “non-interpretable”.
Results :
There were 34 irradiated UM enucleated eyes compared to 47 non-irradiated UM eyes (controls). BAP1 IHC was non-interpretable in 7/81 (9%) eyes (4 irradiated and 3 non-irradiated). There was no significant difference between irradiated and non-irradiated UM with respect to nBAP1 IHC (lost in 41% vs 51%, p=0.19), ch3 status (monosomy 3 in 59% vs 60%, p=0.48), and outcome (metastatic disease in 44% vs 47%, p=0.8). Correlation of BAP1 IHC with disomy 3 (ch3D), monosomy 3 (ch3M), and outcome [intact BAP1:ch3D and/or no metastasis AND lost BAP1:ch3M and/or metastasis] in irradiated tumors was significantly lower when compared with non-irradiated tumors [21/30 (70%) vs 41/44 (93%), p=0.004*, Bonferroni correction 0.04*]. On re-evaluation of discordant cases, decreased or absent retinal staining overlying the tumor and weak intratumoral control were seen in six irradiated UM, pointing to a false-negative nBAP1 stain. With those cases excluded, the correlation of nBAP1 IHC with ch3 status and outcome was not significantly different in irradiated and non-irradiated UM [18/24 (75%) vs 41/44 (93%), p=0.017*, Bonferroni correction 0.15].
Conclusions :
There are pitfalls in the interpretation of BAP1 immunostain in irradiated UM. This test should be used judiciously in tumors with prior plaque brachytherapy.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.