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MYC expression and translocation analyses in low-grade and transformed follicular lymphoma
- Source :
- Histopathology, 71(6), 960-971. Wiley
- Publication Year :
- 2017
-
Abstract
- 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.
- Subjects :
- Male
Follicular lymphoma
8Q24
Chromosomal translocation
MYC
Translocation, Genetic
Chromosome Breakpoints
0302 clinical medicine
CDKN2A
PROGNOSTIC-SIGNIFICANCE
Lymphoma, Follicular
In Situ Hybridization, Fluorescence
Netherlands
Aged, 80 and over
REARRANGEMENTS
General Medicine
Middle Aged
BCL6
Immunohistochemistry
Gene Expression Regulation, Neoplastic
double-hit
030220 oncology & carcinogenesis
Female
NEOPLASMS
Adult
Histology
DISTINCT
Biology
Pathology and Forensic Medicine
Proto-Oncogene Proteins c-myc
03 medical and health sciences
follicular lymphoma
Median follow-up
medicine
C-MYC
Humans
Aged
Retrospective Studies
CYTOGENETIC ALTERATIONS
transformation
Breakpoint
B-CELL LYMPHOMA
MYC translocation partner
medicine.disease
Molecular biology
PATHOLOGY
PAX5
BURKITT-LYMPHOMA
Follow-Up Studies
030215 immunology
Subjects
Details
- Language :
- English
- ISSN :
- 03090167
- Volume :
- 71
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Histopathology
- Accession number :
- edsair.doi.dedup.....612d9f0a893e5556530a888fd11ad82c