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SLC12A2 as a potential histological marker of ulcerative colitis associated colorectal dysplasia
Merli, Angela-Maria; Vieujean, Sophie; MASSOT, Charlotte et al.
2020Belgian Week of Gastroenterologyw
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Abstract :
[en] Introduction: Patients suffering from ulcerative colitis (UC) are at increased risk of developing dysplasia (DAI) and colorectal cancer (CAC). Differentiating DAI from inflammation remains difficult for both endoscopists and anatomopathologists due to macro and microscopic features shared by these lesions. Aim: The aim of our work was to confirm, by histological evaluation, a potential proteomic biomarker discriminating early DAI lesions from chronic inflamed and normal tissues in UC. Methods: We included 15 paired tissues from UC patients (n=5) presenting low-grade DAI. Epithelial cells were isolated by laser capture microdissection and analyzed by label-free proteomics. We selected one protein differentially distributed between DAI, inflamed (I) and normal (N) tissues for confirmation by immunochemistry (IHC). IHC characterization was performed using both the staining intensity score (0 to 4) and the staining pattern: “gradient” (staining intensity increasing from the epithelium lumen to the bottom of the crypts) or “no gradient” (homogenous staining). UC patients with DAI (n=28), dysplastic lesion in non-inflammatory colon (DSp) (n=9), CAC (n=14) and at high risk of CAC (>10 years of UC duration) but free of dysplasia or cancer (n=23) were included. We further studied this potential marker tissue distribution in the mouse model of CAC (AOM/DSS treated mice) to trace its presentation at different evolution stages and assessed low (n=51), high-grade DAI (n=35) and CAC (n=38), as well as relevant paired control tissues. This potential tissue marker was finally evaluated in sporadic precancerous colorectal lesions of UC-free patients with low (n=19) and highgrade (n=16) adenomas and cancerous lesions (CRC): pT1 to pT4 (n=82) and compared to paired normal tissues when available. Results: Proteomics identified 1070 proteins among which 19 showed a differential distribution between DAI and I or N. The sodium chloride co-transporter SLC12A2 was only identified in DAI. SLC12A2 IHC “no gradient” staining pattern was associated to DAI and DSp compared to I or N (with p <0.0001 and 0.0002 respectively). The IHC score was also higher for DAI, DSp and CAC compared to paired I and N (p<0.0001 and 0.0084 respectively). These results were confirmed from low-grade dysplasia to more advanced lesions in the AOM/DSS mice model. The “no gradient” pattern was also significantly associated to low and high-grade adenomas, and CRC of UC-free patients compared to normal control tissues. The sensitivity and specificity of SLC12A2 histological pattern reached 89% and 95% for DAI versusI; 90% and 93% for CAC and/or DAI versus I. In addition, the sensitivity and specificity reached 99% and 87% for all precancerous and cancerous lesions (DAI, DSp, CAC and CRC) versus N and I (including also non-progressing UC patients). Conclusions: A specific histological pattern for SLC12A2 is associated to precancerous and cancerous colorectal lesions, and is able to be discriminate these lesions from inflammation and normal tissue in UC. The continuous upregulation of SLC12A2 in advanced colorectal lesionsin the CAC mice model also suggests a role of this protein in the pathophysiology of inflammation-associated colon neoplasia.
Disciplines :
Gastroenterology & hepatology
Author, co-author :
Merli, Angela-Maria ;  Université de Liège - ULiège > I3-Translational gastroenterology
Vieujean, Sophie  ;  Université de Liège - ULiège > I3-Translational gastroenterology
MASSOT, Charlotte ;  Université de Liège - ULiège > I3-Translational gastroenterology
BLETARD, Noëlla ;  Centre Hospitalier Universitaire de Liège - CHU > Unilab > Service d'anatomie et cytologie pathologiques
QUESADA CALVO, Florence ;  Université de Liège - ULiège > I3-Translational gastroenterology
Baiwir, Dominique  ;  Université de Liège - ULiège > GIGA Platforms
Mazzucchelli, Gabriel  ;  Université de Liège - ULiège > Département de chimie (sciences) > Laboratoire de spectrométrie de masse (L.S.M.)
Servais, Laurence ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : GIGA - Cardiovascular Sciences
WERA, Odile ;  Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Centre d'oncologie
Oury, Cécile  ;  Université de Liège - ULiège > Cardiovascular Sciences-Cardiology
de Leval, Laurence ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
Sempoux, Christine
Manzini, Roberto;  University Hospital Zurich > Division of Gastroenterology and Hepatology
Scharl, Michael;  University Hospital Zurich > Division of Gastroenterology and Hepatology
Rogler, Gerhard;  University Hospital Zurich > Division of Gastroenterology and Hepatology
De Pauw, Edwin  ;  Université de Liège - ULiège > Département de chimie (sciences) > Chimie analytique inorganique
COIMBRA MARQUES, Carla ;  Centre Hospitalier Universitaire de Liège - CHU > Département de chirurgie > Chirurgie abdo, sénologique, endocrine et de transplantation
COLARD, Arnaud ;  Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service de gastroentérologie, hépatologie, onco. digestive
Vijverman, Anne;  Centre Hospitalier Régional de la Citadelle (Liège) - CHR CITADELLE > Department of Gastroenterology
DELVENNE, Philippe ;  Centre Hospitalier Universitaire de Liège - CHU > Unilab > Service d'anatomie et cytologie pathologiques
Meuwis, Marie-Alice  ;  Université de Liège - ULiège > I3-Translational gastroenterology
LOUIS, Edouard  ;  Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service de gastroentérologie, hépatologie, onco. digestive
More authors (12 more) Less
Language :
English
Title :
SLC12A2 as a potential histological marker of ulcerative colitis associated colorectal dysplasia
Publication date :
04 March 2020
Event name :
Belgian Week of Gastroenterologyw
Event place :
Antwerp, Belgium
Event date :
du 4 au 6 mars 2020
Peer reviewed :
Peer reviewed
Available on ORBi :
since 16 February 2020

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