Open AccessBim Expression in Peritumoral Lymphocytes is Associated with Survival in Patients with Metastatic Clear Cell Renal Cell Carcinoma
Author(s) -
Bimal Bhindi,
Elizabeth Bearrick,
John C. Cheville,
Christine M. Lohse,
Ross Mason,
Paras Shah,
Susan Harrington,
Henan Zhang,
Haidong Dong,
Stephen A. Boorjian,
R. Houston Thompson,
Bradley C. Leibovich
Publication year - 2021
Publication title -
kidney cancer
Language(s) - English
Resource type - Journals
eISSN - 2468-4570
pISSN - 2468-4562
DOI - 10.3233/kca-210116
Subject(s) - nephrectomy , medicine , renal cell carcinoma , clear cell renal cell carcinoma , immunohistochemistry , oncology , proportional hazards model , kidney cancer , cancer , metastasis , clear cell , pathology , kidney
BACKGROUND: Bim (BCL-2-interacting mediator of cell death) is a downstream pro-apoptotic signaling molecule activated by the PD-1 pathway. OBJECTIVE: We sought to determine if Bim expression in peritumoral T-lymphocytes (PTLs) is associated with survival in patients with metastatic clear cell renal cell carcinoma (ccRCC). METHODS: Immunohistochemistry staining for Bim was performed on paraffin-embedded tumor tissue blocks from patients with metastatic ccRCC who underwent nephrectomy between 1990-2004. Associations of Bim expression with cancer-specific survival (CSS) and overall survival (OS) from date of metastasis were evaluated using multivariable Cox regression models, adjusting for age, sex, and metastases-score. RESULTS: 525 patients with metastatic ccRCC, of whom 169 (32%) had metastases at time of nephrectomy were studied. After multivariable adjustment, high Bim expression remained associated with worse CSS (HR = 1.31; 95% CI 1.07–1.59; p = 0.008) and OS (HR = 1.28; 95% CI 1.06–1.55; p = 0.01). The interaction between Bim and PD-L1 was not statistically significant for CSS (p = 0.68) or OS (p = 0.57), suggesting that the associations between Bim and survival outcomes were not significantly different based on tumor PD-L1 expression. CONCLUSION: High Bim expression in PTLs at nephrectomy is prognostic of worse CSS and OS in patients with metastatic ccRCC, irrespective of tumor PD-L1 expression. The role of earlier PD-1/PD-L1-directed therapy warrants evaluation in these patients.