Good prognosis for follicular lymphoma with estrogen receptor α-positive follicular dendritic cells.

Follicular lymphoma (FL) has a meshwork of follicular dendritic cells (FDCs). We previously demonstrated the presence of estrogen receptor alpha (ERα)+ CD23+ FDCs in grades 1-2 FL. The significance of FDCs as a prognostic factor in FL remains unknown. The current study aimed to compare clinicopathological features, including prognosis, between FL with and without ERα+ FDCs. This study evaluated the clinicopathological significance of ERα expression in 70 FL patients by immunostaining. The presence of ERα mRNA on FDCs from 5 FL patients was confirmed by CD21/ERα double staining (immunohistochemistry and in situ hybridization). We defined patients with frequent ERα expression as the ERαhigh group and those with infrequent ERα expression as the ERαlow group. Thirty-two patients were assigned to the ERαhigh group (45.7%), and 38 patients were assigned to the ERαlow group (54.3%). Both overall survival (OS) and progression-free survival (PFS) were significantly better in the ERαhigh group than in the ERαlow group (OS, log-rank, P = .0465; PFS, log-rank, P = .0336). Moreover, high ERα expression on FDCs was an independent prognostic factor for OS in both the univariate ([hazard ratio] HR, 0.163; P = .0260) and multivariate (HR, 0.050; P = .0188) analyses and for PFS in both the univariate (HR, 0.232; P = .0213) and multivariate (HR, 0.084; P = .0243) analyses. ERα mRNA expression was detected in CD21+ FDCs within the neoplastic follicles of FL patients. In conclusion, a neoplastic follicular microenvironment with ERα-positive FDCs might affect the grade and presence of the follicular pattern of FL and improve patient prognosis.

Differential expression of estrogen receptor-α on follicular dendritic cells from patients with grade 1-2 and grade 3 follicular lymphoma.

Hormone therapy has been used for patients with estrogen receptor alpha (ERα)-positive breast cancers. Recently, some studies reported the expression of ERα on neoplastic cells from B-cell lymphomas. However, there has been only one report of ERα expression on the follicular dendritic cells (FDCs) that structurally and functionally support the microenvironment of follicular lymphomas (FLs). The objective of this study was to investigate the frequency of ERα expression on FDCs in nonneoplastic reactive lymphoid tissues and to compare the frequency of ERα expression on FDCs in the axillary lymph nodes between patients with and without antiestrogen therapy and among patients with grades 1-3 of FL. Reverse transcription-polymerase chain reaction was performed to detect ERα mRNA in FL. In nonneoplastic germinal centers (GCs) from patients with tonsillitis or reactive lymphadenitis, ERα was expressed in the light zone. ERα-positive cells strongly correlated with the width of GCs (rs  = 0.81, P < 0.01) and the CD21-positive (rs  = 0.69, P < 0.01) and CD23-positive (rs  = 0.83, P < 0.01) FDC meshwork. The axillary lymph nodes had fewer ERα-positive cells, smaller GCs, and a looser CD21- and CD23-positive FDC meshwork with hormone therapy than without hormone therapy (P < 0.01). Neoplastic follicles of G1-2 FL had more ERα-positive cells and a larger CD23+ FDC meshwork than those of G3 FL (P < 0.01). ERα mRNA was detected in both G1-2 FL and G3 FL by reverse transcription-polymerase chain reaction. In conclusion, these results suggested that antiestrogen hormone therapy may decrease the number of ERα-positive FDCs and that the responses mediated by the estrogen-ERα interaction on FDCs may differ between G1-2 FL and G3 FL.