TP53.STATUS.IN.MANTLE.CELL.LYMPHOMA.(MCL).9.A.109YEAR.SINGLE.CENTER.
EXPERIENCE.
.
Ezzat% Elhassadi1,% Brian% Hennessy1,% Santhil% Kumar2,% Christine% Shilling1,% Dawn% Swan1%and% Mark%
Catherwood3%
%
(1)University1 Hospital1 Waterford,1 Waterford,1 Ireland,1 (2)University1 Hospital1 Waterfrod,1 Waterford,1
Ireland,1(3)Molecular1Department1,1Belfast1University1Hospital,1Belfast,1Ireland1
1
Mantle%Cell%Lymphoma%(MCL)%is%a%rare%subUtype%of%BUcell%nonUHodgkin%lymphoma%(NHL),%with%
variable%course.%Most%of%patients%with%this%disease%has%an%aggressive%clinical%course%and%poor%
prognosis.% However,% a% minority% of% patient% may% survive% untreated% for% many% years.% MCL% is%
responsive%to%a%variety%of%initial%therapies,%but%relatively%shortUterm%remissions%are%achieved%
with%conventional%chemotherapy%regimens.%The%median%duration%of%remission%in%most%trials%
using%standard%chemoUimmunotherapy%is%1.5–3%years%and%the%median%overall%survival%(OS)%is%
3–6% years.%TP531mutation% confers% a% dismal% prognosis% in% MCL% with% a% median% survival% of% 1.3%
years.%The%aim%of%this%study%was%to%further%investigate%the%mutation%profile%and%prognostic%
impact% of%TP53%mutations% in% our% cohort% of% 29% MCL% patients% over% the% study% period% (2006U
2016).%In%addition,%to%correlate%the%TP531mutational%status%with%p53%expression%by%immunoU
histochemistry%(IHC).%We%analysed%32%tumour%DNA%samples%(including%2%samples%at%relapsed%
disease)%for%evidence%of%TP531disruption%using%p53%expression%on%IHC,%Sanger%sequencing%and%
next%generation%sequencing%(NGS)%if%indicated.%
The% median% age% at% diagnosis% was% 65% years% (range,% 36–88% years),% with% male% predominate%
(72%).%As%expected,%OS%was%significantly%shorter%among%MCL%cases%with%high%MIPI%score%than%
among% MCL% cases% with% low% MIPI% score% (median% 4.3% years% vs% unreached% ,%P=0.03,% log% rank%
test).%p53%expression%using%IHC%(>%30%)%correlate%strongly%(100%)%with%TP53%mutation%status%
confirmed% with% sequencing.% The%TP531mutation% frequency% in% this% study% reported% as% 21%%
comparable%to%reported%literatures.%The%median%OS%and%PFS%for%the%entire%cohort%were%6.5%
and% 3% years% respectively.% Eleven% (28%)% deaths% that% were% accounted% in% this% study% with% five%
(45%)% deaths% which% were% lymphoma% related.% Most% of% MCL% patients%
harbouring%TP53%mutations% have% aggressive% disease% course% with% multiple% relapses% and%
lymphoma%related%deaths%(80%).%In%subUset%analysis,%the%impact%of%TP531mutation%was%clearly%
apparent%on%patient%survival%,%the%OS%was%only%4%years%in%TP53%mutated%disease%and%was%not%
reached%in%the%wildUtype%TP53%cohort%(P%=%0.007).%
Our% data% confirmed% the% dismal% outcome% of% MCL% in% presences% of%TP53%disruption% and% the%
strong% correlation% between% p53% expression% and% the% mutation% status,% of% which% will% be%
incorporated%in%our%routine%initial%histological%assessment.%We%intend%to%expand%this%project%
nationally% to% overcome% the% sample% size% limitations% and% advocating% upfront% use% of% novel%
therapies%in%TP53Udisrupted%disease%in%larger%clinical%trials.%%
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