BCL-6 Expression in Mesenchymal Tumors: An Immunohistochemical and Fluorescence In Situ Hybridization Study.
Matthew P Walters, Andrew L Folpe. Mayo Clinic, Rochester, MN
Background: The BCL-6 proto-oncogene encodes a transcriptional repressor protein, best known for its regulatory role in germinal center lymphocyte differentiation and survival. Among normal tissues, BCL-6 expression at a level detectable by immunohistochemistry (IHC) is typically confined to germinal center B-cells and a subpopulation of T-helper cells. Very little is known about BCL-6 expression in mesenchymal tissues. Prompted by a recent case of solitary fibrous tumor (SFT) showing strong BCL-6 immunoreactivity, we examined a series of SFT and other spindle cell mesenchymal tumors for BCL-6 expression.
Design: Formalin-fixed, paraffin-embedded tissue sections from 55 mesenchymal tumors [26 SFT (19 benign/uncertain, 7 malignant), 6 synovial sarcomas (SS), 5 GIST, 5 MPNST, 5 leiomyosarcomas (LMS), 4 desmoid tumors (DT), 4 perineuriomas (PN)] were immunostained for BCL-6 using a commercial antibody and the Dako Envision system. Cases were scored as "negative", "1+" (5-25% positive), "2+" (26-50% positive) and "3+" (>51% positive). Only nuclear immunoreactivity was considered positive. Appropriate controls were employed. Six BCL-6 positive SFT were also tested for BCL-6 gene rearrangement/amplification by FISH, using previously published methods.
Results: Nuclear expression of BCL-6 was seen in 13/26 SFT (1+:7, 2+: 6), 5/5 LMS (2+:3, 3+:3), 5/6 SS (1+:4, 2+:1), 1/5 GIST (2+), 1/5 MPNST (2+), 1/4 PN (1+), and 0/5 DT. BCL-6 expression was significantly more frequent in malignant (6/7) as compared with benign/uncertain SFT (6/19) (p=0.02, Fishers Exact Test). FISH for BCL-6 rearrangement/amplification was negative in all tested cases.
Conclusions: In this, the first study to date of BCL-6 expression in mesenchymal tumors, we have observed strong (2-3+) BCL-6 expression in 50% or more of SFT, SS, and LMS, and in a lesser percentage of GIST, MPNST and PN. Given these findings, it is doubtful that there is a role for BCL-6 IHC in the differential diagnosis of spindle cell tumors. Significantly more frequent expression of BCL-6 in malignant as compared with benign/uncertain SFT suggests that abnormalities in the BCL-6 signalling pathway may contribute to malignant transformation in at least some mesenchymal tumors. Based on our (limited) FISH data, it is unlikely that BCL-6 expression in mesenchymal tumors is due to BCL-6 gene amplification or rearrangement. With the development of new therapeutic agents targeting the BCL-6 pathway, IHC for BCL-6 may potentially be of value in predicting response to such agents in patients with aggressive or unresectable disease.
Category: Bone & Soft Tissue
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 20, Tuesday Morning