Tumor infiltrating T-cells and loss of expression of SWI/SNF genes in varying stages of clear cell renal cell carcinoma

被引:0
|
作者
Hrizat, Alaa S. [1 ]
Lin, Ruihe [1 ]
Eberle-Singh, Jaime [1 ]
O'Neill, Raymond [1 ]
Xia, Yan [2 ]
Testa, Joseph R. [3 ]
Uzzo, Robert [4 ]
Mccue, Peter A. [3 ]
Yang, Haifeng [1 ]
Li, Li [1 ,5 ]
机构
[1] Thomas Jefferson Univ Hosp, Dept Pathol & Genom Med, Philadelphia, PA USA
[2] Arnot Ogden Med Ctr, Dept Labs, Elmira, NY USA
[3] Fox Chase Canc Ctr, Dept Pathol, Philadelphia, PA USA
[4] Fox Chase Canc Ctr, Dept Surg Oncol, Philadelphia, PA USA
[5] Norfolk Gen Hosp, Phys Sci Med Grp, Norfolk, VA USA
关键词
Tumor immune microenvironment; Clear cell renal cell carcinoma; SWI/SNF genes; COMPLEX; SUPPRESSOR; EVEROLIMUS; SURVIVAL; ARID1A; ROLES; LINKS; PBRM1;
D O I
10.1016/j.prp.2024.155774
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Background: Patients with clear cell renal cell carcinoma (ccRCC) metastases face poor prognoses, even with adjuvant therapies. Tumor-infiltrating T-cells and macrophages are critical in targeting tumor cells within the renal microenvironment. Beyond VHL mutations, loss-of-function mutations in SWI/SNF complex genes, including PBRM1, BAP1, ARID1A, SETD2, SMARCA4 (BRG1), and SMARCA2 (BRM), have been implicated in ccRCC progression. Design: A tissue microarray of 160 ccRCC cases was analyzed via immunohistochemistry (IHC) for SWI/SNF protein expression and CD4 + /CD8 +T-cell infiltration. Clinical and pathologic features were obtained through electronic medical records. Statistical analyses included one-way ANOVA, two-way ANOVA, Pearson's chisquare and t-tests. Results: Loss of SWI/SNF protein expression was observed in PBRM1 (31 %), ARID1A (51 %), SETD2 (14 %), BRG1 (15 %), BRM (38 %), and BAP1 (40 %). T-cell counts varied significantly with stage: CD4 + counts peaked at Stage 3, while CD8 + counts increased through Stage 4 (p G 0.001). Loss of PBRM1 was more frequent in advanced stages (29.4 %, p G 0.001), while BRM and BRG1 losses were more common in earlier stages (p G 0.001, p = 0.006). ARID1A and BRM losses correlated with reduced CD8 + counts (p = 0.016, p = 0.032) and stage-specific CD4 + variations (p G 0.001, p = 0.042). Conclusion: Loss of PBRM1, SMARCA2/BRM, and SMARCA4/BRG1 expression is significantly associated with ccRCC progression, with PBRM1 loss prevalent in advanced stages and SMARCA2/BRM and SMARCA4/BRG1 in earlier stages. ARID1A and SMARCA2/BRM losses correlate with reduced CD8 + counts and stage-specific CD4 + infiltration, highlighting their potential as biomarkers for disease progression and immunotherapeutic response.
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页数:6
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