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

Abstract

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 ( r s = 0.81, P < 0.01) and the CD21‐positive ( r s = 0.69, P < 0.01) and CD23‐positive ( r s = 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.

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

“…ERα reactivity was estimated as previously described. 15 Briefly, cells positive for ERα were counted in five neoplastic follicles for each case. In FL specimens with diffuse proliferation, positive reactions were counted in five high-power fields .…”

“…In FL specimens with diffuse proliferation, positive reactions were counted in five high-power fields . 15 Therefore, we estimated ERα/HPF as a semi-quantitative marker of the width of ERα + CD23 + FDC meshwork in this study.…”

“…The area of the neoplastic follicle was determined from images and estimated as the gross area by ImageJ as previously described. 15,18,19 The CD23 + FDC pattern was divided into 2 groups: none/dim or focal/marginal 4 /diffuse.…”

“…In the IHC analysis, ERα expression was detected mainly in FDCs in neoplastic follicles, as previously reported. 15 OS, PFS, and ERα/HPF were compared between the ERα high-expression (ERα high ) and ERα low-expression (ERα low ) groups. As a result, most of the significant differences in OS and PFS were observed when FL patients were divided into 2 groups: ≥ 3 ERα/HPF and <3 ERα/HPF.…”

“…14 We previously demonstrated that the number of ERα + cells was positively correlated with the width of the CD23 + FDC meshwork in both nonneoplastic GC and neoplastic follicle, and that estrogen receptor alpha (ERα) + CD23 + FDCs supported the neoplastic follicular microenvironment of grades 1-2 (G1-2) FL, but not G3 FL, suggesting the possibility of the usefulness of antiestrogen therapy against FL. 15 This study first compared clinicopathological features and prognosis between FL patients with more and less frequent ERα + FDCs and investigated the significance of ERα + FDCs in the FL microenvironment.…”