- •Retrospective analysis of FFPE primary lymph node tissue from patients with MCL identified secondary cytogenetic abnormalities in 82% of samples.
- •FFPE primary lymph node tissue can be used to detect secondary cytogenetic abnormalities in Mantle cell lymphoma, particularly those associated with a more aggressive disease.
- •Conventional karyotyping of bone marrow or trephine is not the best assay to detect relevant cytogenetic abnormalities in patients with MCL.
- •Immunohistochemistry is an inexpensive screening tool to direct FISH testing for CCND1-IGH fusion, MYC rearrangements and loss of ATM.
Mantle Cell Lymphoma (MCL), is characterised by the reciprocal translocation t(11;14) resulting in CCND1-IGH gene fusion and subsequent upregulation of the CCND1 gene. Rearrangements of MYC and losses of CDKN2A and TP53 have been identified as biomarkers informing prognostic and potentially therapeutic information however these are not routinely assessed in MCL investigation. We aimed to identify additional cytogenetic changes using fluorescence in situ hybridisation (FISH) on formalin fixed paraffin embedded (FFPE) primary lymph node tissue microarrays in a cohort of 28 patients diagnosed with MCL between 2004 and 2019. FISH results were compared with corresponding immunohistochemistry (IHC) biomarkers to determine if IHC was a reliable screening tool to direct FISH testing.
FFPE lymph node tissue samples were constructed into tissue microarrays (TMA) which were stained with 7 immunohistochemical biomarkers: Cyclin D1, c-Myc, p16, ATM, p53, Bcl-6 and Bcl-2. The same TMAs were hybridised with FISH probes for the corresponding genes; CCND1-IGH, MYC, CDKN2A, ATM, TP53, BCL6 and BCL2. FISH and the corresponding IHC biomarkers were analysed to determine if secondary cytogenetic changes could be identified and if IHC could be used as a reliable, inexpensive predictor of FISH abnormalities to potentially direct FISH testing.
CCND1-IGH fusion was detected in 27/28 (96%) of samples. Additional cytogenetic changes were identified by FISH in 15/28 (54%) of samples. Two additional abnormalities were detected in 2/28 (7%) samples. Cyclin D1 IHC overexpression was an excellent predictor of CCND1-IGH fusion. MYC and ATM IHC were useful screening tests to direct FISH testing and identified cases with poor prognostic features including blastoid change. IHC did not show clear concordance with FISH for other biomarkers.
FISH using FFPE primary lymph node tissue can detect secondary cytogenetic abnormalities in patients with MCL which are associated with an inferior prognosis. An expanded FISH panel including MYC, CDKN2A, TP53 and ATM should be considered in cases where anomalous IHC expression or is seen for these markers or if the patient appears to have the blastoid variant of the disease.
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Published online: April 17, 2023
Accepted: April 14, 2023
Received in revised form: April 7, 2023
Received: September 24, 2021
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