BAP1 Loss as a Marker of Aggressive Clear Cell Renal Cell Carcinoma: Three Cases With Spinal Metastases.

Mutations play a pivotal role in the pathogenesis of renal cell carcinoma. Among these, alterations in the BRCA1-associated protein 1 (BAP1) gene are frequently identified in clear cell renal cell carcinoma (ccRCC) and have emerged as adverse prognostic and predictive biomarkers. We present three cases illustrating BAP1 loss as a key molecular event in a subset of ccRCC associated with aggressive clinical behavior and potential resistance to immunotherapy. Three patients with ccRCC and histologically confirmed thoracic vertebral metastases were retrospectively reviewed. All three demonstrated loss of BAP1 immunostaining and presented with symptomatic spinal involvement at initial diagnosis. None exhibited a meaningful clinical response to localized palliative radiotherapy or to systemic therapy consisting of immunotherapy in combination with axitinib. These observations suggest that BAP1 loss in ccRCC may be associated with early spinal metastatic presentation, reduced survival, and resistance to commonly used therapeutic regimens. Incorporating routine immunohistochemical assessment of BAP1 status into diagnostic evaluation may facilitate earlier identification of aggressive disease and support the development of more individualized treatment strategies aimed at improving clinical outcomes.