Expression of BAFF and BAFF-R in follicular lymphoma: correlation with clinicopathologic characteristics and survival outcomes

Abstract

Background: B-cell activation factor (BAFF) and BAFF-receptor (BAFF-R) play crucial roles in the viability and proliferation of malignant lymphoma cells. Limited information exists regarding expression profiles and the prognostic role of BAFF and BAFF-R in follicular lymphoma (FL). We sought to determine the expression profiles of BAFF and BAFF-R in FL and to evaluate the correlation of BAFF and BAFF-R expression with clinicopathologic characteristics and outcome of FL. Correlation between expression levels of BAFF detected by immunohistochemical (IHC) and serum levels of BAFF was also evaluated.

Methods: Paraffin-embedded specimens from 115 patients were immunohistochemically examined for BAFF and BAFF-R expression. Expression levels were dichotomized into low versus high categories based on immunostaining intensity. The correlation of BAFF and BAFF-R expression with clinicopathologic characteristics and patient outcome was assessed. Serum levels of BAFF in 35 of the 115 patients with IHC data were measured by Enzyme-linked Immunosorbent assay (ELISA).

Results: BAFF and BAFF-R were expressed in 88.7% (102/115) and 87.8% (101/115) of the cases, respectively. BAFF expression was significantly correlated with only one clinicopathologic feature: Ann Arbor stage. No significant correlation was found between expression levels of BAFF detected by IHC and serum levels of BAFF detected by ELISA. High expression of BAFF-R, but not BAFF, was significantly correlated with inferior progression-free survival (PFS; P = 0.013) and overall survival (OS; P = 0.03). High expression of BAFF-R, bulky disease, and elevated lactate dehydrogenase were correlated with inferior PFS and OS in multivariate analysis. A prognostic scoring system incorporating these 3 risk factors identified 3 distinct prognostic groups with 5-year PFS of 59.4%, 41.9%, and 10.7% and OS of 91.3%, 79.7%, and 45.8%, respectively.

Conclusions: Most patients with FL variably express BAFF and BAFF-R. High expression of BAFF-R, but not BAFF, may be an independent risk factor for PFS and OS in FL.

Figure 1. Typical distributions of BAFF and BAFF-R expression in follicular lymphoma (FL) and representative cases with different immunostaining intensity for BAFF and BAFF-R.

(A) Distribution of BAFF expression in tumor specimen of FL. (B) Distribution of BAFF-R expression in tumor specimen of FL. (C) Negative staining (−) for BAFF. (D) Weak staining (1+) for BAFF. (E) Moderate staining (2+) for BAFF. (F) Strong staining (3+) for BAFF. (G) Negative staining (−) for BAFF-R. (H) Weak staining (1+) for BAFF-R. (I) Moderate staining (2+) for BAFF-R. (J) Strong staining (3+) for BAFF-R.

Figure 2. Progression-free survival (PFS) and overall survival (OS) for 115 patients with follicular lymphoma according to BAFF and BAFF-R expression levels.

(A) No significant difference in PFS was noted between low- and high-BAFF expression groups (P = 0.929). (B) No significant difference in OS was noted between low- and high-BAFF expression groups (P = 0.647). (C) Patients with high-BAFF-R expression showed significant inferior PFS (P = 0.013). (D) Patients with high-BAFF-R expression showed significant inferior OS (P = 0.03).

Figure 3. Progression-free survival (PFS) and overall survival (OS) for 50 patients with follicular lymphoma treated with rituximab ± chemotherapy according to BAFF and BAFF-R expression levels.

(A) No significant difference in PFS was noted between low- and high-BAFF expression groups (P = 0.652). (B) No significant difference in OS was noted between low- and high-BAFF expression groups (P = 0.251). (C) No significant difference in PFS was noted between low- and high-BAFF-R expression groups (P = 0.201). (D) No significant difference in OS was noted between low- and high-BAFF-R expression groups (P = 0.236).

Figure 4. Progression-free survival (PFS) and overall survival (OS) for 64 patients with follicular lymphoma treated with non-rituximab regimens according to BAFF and BAFF-R expression levels.

(A) No significant difference in PFS was noted between low- and high-BAFF expression groups (P = 0.96). (B) No significant difference in OS was noted between low- and high-BAFF expression groups (P = 0.768). (C) Patients with high-BAFF-R expression showed significant inferior PFS (P = 0.028). (D) Patients with high-BAFF-R expression showed significant inferior OS (P = 0.044).

Figure 5. Progression-free survival (PFS) and Overall survival (OS) for all 115 patients with follicular lymphoma according to the prognostic scoring system incorporating the 3 independent risk factors for both PFS and OS.

(A) Increasing scores correlated with inferior PFS (P<0.001). (B) Increasing scores correlated with inferior OS (P<0.001). LR, low risk group (patients with no risk factor); IR, intermediate risk group (patients with 1 risk factor); HR, high risk group (patients with 2–3 risk factors).