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MYC expression and translocation analyses in low-grade and transformed follicular lymphoma

Aukema, S. M., van Pel, R., Nagel, I., Bens, S., Siebert, R., Rosati, S., van den Berg, E., Bosga-Bouwer, A. G., Kibbelaar, R. E., Hoogendoorn, M., van Imhoff, G. W., Kluin-Nelemans, H. C., Kluin, P. M. & Nijland, M., Dec-2017, In : Histopathology. 71, 6, p. 960-971 12 p.

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  • MYC expression and translocation analyses in low-grade and transformed follicular lymphoma

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AimsLow-grade follicular lymphoma (FL) (grade 1/2, FL1/2) has an annual risk of transformation of approximate to 3%, which is associated with aberrations in CDKN2A/B, TP53, and MYC. As in diffuse large B-cell lymphoma, high MYC expression in transformed FL (tFL) might predict a MYC breakpoint.

Methods and resultsWe quantified MYC expression by immunohistochemistry and digital analysis in 41 paired biopsies from 20 patients with FL1/2 with subsequent transformation and in four isolated biopsies of tFL. As controls, 28 biopsies of FL1/2 without transformation (median follow-up of 105 months) and nine biopsies of FL3A/B were analysed. In the 20 FL1/2-tFL pairs, MYC expression was significantly higher in tFL than in the initial FL1/2 biopsies (median 54% versus 6%; 7% in FL3A, and 35% in FL3B). MYC breaks (MYC-R) were detected in eight of 21 (38%) tFLs analysed by fluorescence in-situ hybridization (FISH), with a median MYC score of 86%. In two of the analysed tFL cases, the translocation was already detected in antecedent FL1/2. MYC partners were immunoglobulin (IG) loci in three of eight cases (one IGL, one IGH, and one IGK) and non-IG in five of eight cases (two PAX5, one BCL6, and two unknown). Of the eight MYC-R+ cases, six were BCL2+/MYC+ double-hit, one was BCL2+/BCL6+/MYC+ triple-hit, and one was MYC+ single-hit. All three IG-MYC+ cases showed a MYC expression level of >85%, whereas the five cases with a non-IG MYC partner had a wider range of expression (median 68%, range 13-86%). Among the 13 MYC-R- tFLs, two groups with almost dichotomous MYC expression could be observed (three cases showed 90% MYC expression), suggesting alternative mechanisms of MYC activation.

Conclusionswe show an increase in MYC expression from FL1/2 to tFL. MYC breakpoints were present in approximate to 40% of the cases, which is markedly higher than in de novo DLBCL. MYC expression was uniformly high in cases with an IG-MYC translocation but much more heterogeneous and in part independent of the presence of a MYC break in non-IG-MYC and MYC-negative cases.

Original languageEnglish
Pages (from-to)960-971
Number of pages12
JournalHistopathology
Volume71
Issue number6
Publication statusPublished - Dec-2017

    Keywords

  • double-hit, follicular lymphoma, MYC, MYC translocation partner, transformation, B-CELL LYMPHOMA, BURKITT-LYMPHOMA, PROGNOSTIC-SIGNIFICANCE, CYTOGENETIC ALTERATIONS, C-MYC, REARRANGEMENTS, 8Q24, NEOPLASMS, PATHOLOGY, DISTINCT

ID: 51215895