Expression in metastatic tissues of BAP1, a gene encoding for a tumor suppressor protein, is a significant marker for progression-free and overall survival in patients with metastatic clear cell renal cell carcinoma (ccRCC), investigators contended.
An analysis of tissue samples from 124 patients with metastatic ccRCC showed that patients with metastatic tissues expressing BAP1 had a 5-year overall survival (OS) rate of 53.2%, compared with 35.1% for patients whose tissues did not express the gene (P = .004), reported, and colleagues from the A.C. Camargo Cancer Center in Sao Paulo.
BAP1 expression was also associated with significantly better progression-free survival (PFS), but expression of a different gene thought to be associated with prognosis in metastatic ccRCC, PBRM1, was not a significant predictor of either overall survival (OS) or PFS.
“The pattern of immunohistochemical expression of both PBRM1 and BAP1 was shown to be significantly discordant when comparing the expression of primary tumor and metastatic tumor tissue. The use of prognostic biomarkers identified in the primary tumor tissue might be not reliable in the metastatic disease scenario. Patients with metastatic ccRCC that present loss of BAP1 expression in metastatic tissue demonstrated poor survival rates and represent a relevant risk group for tumor recurrence and death,” the investigators wrote in.
Both BAP1 and PBRM1 have been shown to be frequently mutated in ccRCC. These and other mutated genes recently identified through next-generation sequencing encode proteins that are involved in chromatin regulation and act as gene suppressors.
To see whether expression of the genes had prognostic value, they performed immunohistochemical studies of tissues from 124 consecutive patients in their center who underwent metastasectomy or biopsy of metastases and from 38 paired cases with tissues from the primary tumors of patients who underwent partial or radical nephrectomies.
They found that 98 of the metastatic samples (79%) stained negative for PBRM1 and 26 (21%) stained positive for expression of the gene; 62.1% of samples were negative for BAP1 expression and 37.9% were positive.
There were discordant expression patterns between primary tumors and metastases for BAP1 in 17 of the 38 (44.7%) samples from patients with both primary and metastatic tissues and for PBRM1 in 19 of 38 (50%) samples.
As noted before, the 5-year OS rate was 53.2% for patients with BAP1-positive metastases, compared with 35.1% for patients with BAP1-negative tissues (P = .004). The respective 5-year PFS rates for BAP1 expression were 14.9% and 3.9% (P = .003).
There were no significant differences associated with PBRM1 expression for either PFS or OS, however.
Negative expression of BAP1 in metastases was associated in multivariate analysis with both higher risk of death (hazard ratio, 2.017; P = .045) and with disease progression (HR, 1.586; P = .012).
The finding of discordance in expression between the primary tumor and metastases shows that the “strategy of using tissue markers of the primary tumor in the prediction of response of metastatic disease is not reliable. Such fact reinforces the imminent need for identification and validation of tumor markers in metastatic tissue,” the authors wrote.
No funding source or author disclosures were reported.
SOURCE: da Costa WH et al. Urol Oncol. 2018 Nov 13. doi: 10.1016/j.urolonc.2018.10.017.