SLC12A2; colorectal neoplasia; dysplasia associated to inflammation
Abstract :
[en] BACKGROUND AND AIMS: Ulcerative colitis (UC) patients have a greater risk of developing colorectal cancer through inflammation-dysplasia-carcinoma sequence of transformation. The histopathological diagnosis of dysplasia is therefore of critical clinical relevance, but dysplasia may be difficult to distinguish from inflammatory changes. METHODS: A proteomic pilot study on 5 UC colorectal dysplastic patients highlighted proteins differentially distributed between paired dysplastic, inflammatory and normal tissues. The best candidate marker was selected and immunohistochemistry confirmation was performed on AOM/DSS mouse model lesions, 37 UC dysplasia, 14 UC cancers, 23 longstanding UC, 35 sporadic conventional adenomas, 57 sporadic serrated lesions and 82 sporadic colorectal cancers. RESULTS: Differential proteomics found 11 proteins significantly more abundant in dysplasia compared to inflammation, including Solute carrier family 12 member 2 (SLC12A2) which was confidently identified with 8 specific peptides and was below the limit of quantitation in both inflammatory and normal colon. SLC12A2 immunohistochemical analysis confirmed the discrimination of preneoplastic and neoplastic lesions from inflammatory lesions in mice, UC and in sporadic contexts. A specific SLC12A2 staining pattern termed "loss of gradient" reached 89% sensitivity, 95% specificity and 92% accuracy for UC-dysplasia diagnosis together with an inter-observer agreement of 95.24% (multirater κfree of 0.90; IC95%: 0.78 - 1.00). Such discrimination could not be obtained by Ki67 staining. This specific pattern was also associated with sporadic colorectal adenomas and cancers. CONCLUSIONS: We found a specific SLC12A2 immunohistochemical staining pattern in precancerous and cancerous colonic UC-lesions which could be helpful for diagnosing dysplasia and cancer in UC and non-UC patients.
Vieujean, Sophie ; Université de Liège - ULiège > I3-Translational gastroenterology
MASSOT, Charlotte ; Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Recherche translationnelle en gastroentérologie
BLETARD, Noëlla ; Centre Hospitalier Universitaire de Liège - CHU > Unilab > Service d'anatomie et cytologie pathologiques
QUESADA CALVO, Florence ; Centre Hospitalier Universitaire de Liège - CHU > Gastro-Entérologie-Hépatologie
de Leval, Laurence ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
Sempoux, Christine
Manzini, Roberto
Bluemel, Sena
Scharl, Michael
Rogler, Gerhard
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
Vijverman, Anne
Delvenne, Philippe ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Louis, Edouard ; Université de Liège - ULiège > Département des sciences cliniques > Hépato-gastroentérologie
Meuwis, Marie-Alice ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
Télévie grant 7.4556.19; The Swiss international foundation grant 320030_184756
Funders :
Télévie [BE] Fonds Léon Fredericq [BE] ULiège - Université de Liège [BE] SNSF - Swiss National Science Foundation [CH] FEDER - Fonds Européen de Développement Régional [BE]
Funding text :
This work was supported by Télévie [grant number 7.4553.16 to A-MM], the Léon Fredericq Foundation, and research grant from the Belgian Week of Gastroenterology 2020, as well as from Dr. Falk [Pitch Your Project research grant 2019], ULg internal funding, the Swiss National Science Foundation [grant number 320030_184753 to MS and RM], financial support from the Walloon region and the Fonds Européen de Développement Régional for the GIGA facilities. CO is Research Director at the National Funds for Scientific
Research [F.R.S.-F.N.R.S., Belgium].
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