Immunohistochemical Positivity for Reg1 and IL6: Potential Markers for Distinguishing between Colitis-Associated Dysplasia and Sporadic Adenoma in IBD
Xianyong Gui, Sam K Jensen, Shuhong Liu, Zu-hua Gao. University of Calgary and Calgary Laboratory Services, Calgary, AB, Canada
Background: Distinction between colitis-associated dysplasia (i.e. DALM) and sporadic adenoma in IBD (SA-IBD) is important but problematic. Discriminating markers are needed. We have investigated several proteins related to the link between chronic inflammation and carcinogenesis and/or preferentially altered in colitis-associated carcinoma, including HSP47, Transgelin, Vanin1, Reg1, IL6, IL6Rα, STAT3 and SOCS3, for their potential of being such markers.
Design: In view of no gold standard for defining DALM and SA-IBD, only typical and convincing lesions were selected based on several strict criteria. 20 DALMs (M 16, F 4, 26 to 79 y/o; 7 resections, 13 biopsies; 7 with HGD, and 5 with carcinoma), 21 SAs-IBD (M 11, F 10, 32 to 71 y/o; 1 resection, 20 biopsies; all LGD), and 16 conventional adenomas in non-IBD (CAs) (M 10, F 6, 41 to 77 y/o; all biopsies; all LGD) were included. Tissues encompassing dysplastic epithelium (DE) and adjacent non-dysplastic epithelium (aNDE) were selected for immunostaining the 8 proteins. Immunopositivity was semiquantitated (as -, 1+, 2+, 3+). Comparisons of each protein expression between the 3 groups of dysplasia (on LGD) as well as between DE and aNDE in each group were analyzed.
Results: All proteins expressed similarly in DE in all groups but showed several differences: 1) Increase of Reg1 immunopositivity in DE was less in DALMs than that in SAs-IBD (25% vs 61.9% for 3+, p = 0.024). 2) When using Reg1 =3+ as a marker to discriminate SAs-IBD from DALMs, the sensitivity (SEN), specificity (SPE), and positive predictive value (PPV) was 61.9%, 75%, and 72.2%, respectively; when using IL6 ≥2+ as a marker, the SEN, SPE and PPV was 76.2%, 45%, and 59.3%, respectively; when combining both together, the SEN decreased to 52.4% but SPE increased to 85% and PPV increased to 78.6%. 3) A weak expression of Vanin1, IL6, STAT3 and SOCS3 was commonly seen in aNDE in IBD as compared with that in non-IBD; however, no difference existed between DALMs and SAs-IBD. 4) A positive correlation between DE and aNDE for the intensity of expression of Vanin1, IL6 and STAT3 existed in DALMs (Spearman's rank correlation coefficient = 0.69, 0.70, and 0.73, respectively; all p < 0.005) but not in SAs-IBD.
Conclusions: Assessment for the immunopositivity of Reg1 and IL6, in combination with the correlation between dysplastic and adjacent non-dysplastic mucosa for expression of Vanin1, IL6 and STAT3, could be useful markers for distinguishing between DALMs and SAs-IBD. Further validation in a larger number of cases is needed.
Monday, March 19, 2012 1:00 PM
Poster Session II # 108, Monday Afternoon