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Haematologica. 2019 Jul 11. pii: haematol.2019.219543. doi: 10.3324/haematol.2019.219543. [Epub ahead of print]

Highly sensitive and specific in situ hybridization assay for quantification of SOX11 mRNA in mantle cell lymphoma reveals association of TP53 mutations with negative and low SOX11 expression.

Author information

1
Institute of Pathology and Neuropathology, CCC and University Hospital Tuebingen.
2
Institute of Pathology and Neuropathology, CCC and University Hospital Tuebingen leticia.quintanilla-fend@med.uni-tuebingen.de.

Abstract

SOX11 is a valuable marker to identify biologically and clinically relevant groups of mantle cell lymphoma such as cyclin D1 negative and leukemic non-nodal mantle cell lymphoma. We aimed to establish a sensitive in situ hybridization analysis of SOX11 mRNA allowing its quantification within the histopathological context and compare it with immunohistochemistry and RT-qPCR. Furthermore, TP53 status was correlated with SOX11 mRNA levels. Sixty-six cases were investigated; 58 conventional mantle cell lymphomas, including 6 cyclin D1 negative (46 classic, 12 blastoid) and 8 leukemic non-nodal mantle cell lymphomas. RNAscope was used for the in situ hybridization and the results scored as 0 to 4. Mantle cell lymphoma cases with SOX11 positivity by immunohistochemistry were positive by RNAscope but with different scores. RT-qPCR showed a good correlation with the median of the grouped scores but had a wide variation in individual cases. The SOX11 negative leukemic non-nodal mantle cell lymphomas were also negative by RNAscope. TP53 was mutated in 13/63 (21%) cases, including 5/7 (71%) leukemic non-nodal and 8/56 (14%) conventional mantle cell lymphoma. Interestingly, of the TP53 mutated cases, 9 were in the RNAscope negative/low SOX11 group (9/15; 60%) and 4 in the high SOX11 group (4/36; 11%) (p=.0007). In conclusion, RNAscope is a reliable method to evaluate SOX11 mRNA levels. This study demonstrates the broad range of SOX11 mRNA levels in mantle cell lymphoma. An important finding is the significant correlation of TP53 mutations with negative/low SOX11 mRNA level both in leukemic non-nodal and conventional mantle cell lymphoma.

KEYWORDS:

Aggressive Non-Hodgkin's Lymphoma; RNA in situ hybridization; SOX11; TP53 status; mantle cell lymphoma

PMID:
31296581
DOI:
10.3324/haematol.2019.219543
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