SLC12A2 potential marker of dysplasia associated to inflammation in UC

It remains difficult to reach an anatomopathological diagnosis of dysplasia associated to inflammation (DAI) in UC, especially when tissue inflammation is present. The study by Merli et al. aimed to compare the proteomes of dysplastic, inflammatory, and normal paired tissues [6]. Their approach highlighted specific proteins such as Solute Carrier Family 12 member 2 (SLC12A2) which may aid diagnosis of UC-DAI.

This small study was performed on formalin-fixed, paraffin-embedded samples from UC-DAI (n=5). Epithelial cells from the paired tissues were collected by laser capture microdissection and differentially analysed using label-free proteomics.

Proteomic analysis enabled confident identification of 1,070 proteins, among which 19 proteins showed differential abundance between DAI and inflammatory or normal tissue. Of these, SLC12A2 was only detected in DAI. Tissue distribution of SLC12A2 was assessed by immunohistochemistry on UC-DAI (n=11). Colonic tissues of a colitis-associated cancer mouse model (AOM/DSS) were also evaluated by SLC12A2 immunohistochemistry [7].

The model encompassed LGD (n=39), HGD (n=12), adenocarcinoma (ADC, n=6), inflammatory (n=30) and normal (n=6). SLC12A2 immunohistochemistry on UC cases confirmed a significantly different distribution with DAI>inflammatory (P=0.0001 for bordering epithelium, P=0.002 for crypt epithelia). The distribution for DAI was also higher than normal (P<0.0001 for bordering epithelium, P=0.001 for crypt epithelia). In the AOM/DSS model, SLC12A2 was significantly increased in dysplasia compared with inflammatory and normal tissues (LGD>inflammatory, P<0.0001; LGD>normal, P=0.004; HGD>inflammatory, P<0.0001; HGD>normal, P=0.007). In ADC, results were ADC>inflammatory, P=0.0002; ADC>normal, P=0.009; SLC12A2 was also significantly higher in advanced lesions (HGD>LGD, P=0.012; ADC>LGD, P=0.038).

It was concluded that SLC12A2 could be a potential marker of DAI in UC, as it could distinguish dysplasia from surrounding tissues with inflammation. Proper validation is required to evaluate the power of SLC12A2 as specific immunohistochemical marker useful for clarifying difficult cases currently diagnosed as “indefinite for dysplasia”.