MYC expression and translocation analyses in low-grade and transformed Follicular Lymphoma

Abstract

Low grade follicular lymphoma (FL1/2) has an annual risk of transformation of approximately 3% which is associated with aberrations in CDKN2A/B, TP53 and MYC. Like in DLBCL high MYC expression in transformed FL (tFL) might predict a MYC breakpoint. We quantified MYC expression by immunohistochemistry and digital analysis in 41 paired biopsies from 20 patients with FL1/2 with subsequent transformation and in 4 isolated biopsies of tFL. As controls 28 biopsies of FL1/2 without transformation (median follow up 105 months) and 9 FL3A/B were analyzed. In the 20 FL1/2-tFL pairs MYC expression was significantly higher in tFL than in the initial FL1/2 biopsies (median 54% vs 6%; 7% in FL3A, 35% in FL3B). MYC-breaks (MYC-R+) were detected in 8/21 (38%) of by FISH analyzed tFL with a median MYC score of 86%. In 2 of the analyzed tFL cases the translocation was already detected in antecedent FL1/2. MYC-partners were Immunoglobulin (IG) loci in 3/8 cases (1x IGL, 1x IGH, 1x IGK) and non-IG in 5/8 cases (2x PAX5, 1x BCL6, 2x unknown). Of the 8 MYC-R+ cases 6 were BCL2+/MYC+ double-hit, one a BCL2+/BCL6+/MYC+ triple-hit and one MYC+ single-hit. All 3 IG-MYC positive cases showed MYC expression >85% while the 5 cases with a non-IG MYC partner had a wider range of expression (median 68%, range 13-86%). Among the 13 MYC-R negative tFL two groups with an almost dichotomous MYC expression could be observed (3 cases showed ≥90% MYC expression) suggesting alternative mechanisms of MYC activation.

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