Increasing diagnostic accuracy to grade dysplasia in Barrett’s esophagus using an immunohistochemical panel for CDX2, p120ctn, c-Myc and Jagged1

Abstract

BackgroundPatients with non-dysplastic Barrett’s esophagus (ND-BE) and low-grade dysplasia (LGD) are typically monitored by periodic endoscopic surveillance, while those with high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) are usually treated by more aggressive interventions like endoscopic mucosal resection, ablation or surgery. Therefore, the accurate grading of dysplasia in Barrett’s esophagus (BE) is essential for proper patient care. However, there is significant interobserver and intraobserver variability in the histologic grading of BE dysplasia. The objective of this study was to create an immunohistochemical (IHC) panel that facilitates the grading of BE dysplasia and can be used as an adjunct to histology in challenging cases.Methods100 BE biopsies were re-graded for dysplasia independently by 3 subspecialized gastrointestinal pathologists. IHC staining for CDX2, p120ctn, c-Myc and Jagged1 proteins was then performed and assessed by two separate methods of semi-quantitative scoring. Scores were integrated using a principal component analysis (PCA) and receiver operating characteristic (ROC) curve.ResultsPrincipal component analysis demonstrated the ability of this panel of proteins to segregate ND-BE/LGD and HGD/EAC, as the expression of the four proteins is significantly altered between the two subsets. Analysis of the receiver operating characteristic curve showed that this panel has the potential to aid in the grading of dysplasia in these two subcategories with both high sensitivity and specificity. While not able to discriminate between ND-BE and LGD, this panel of four proteins may be used as an adjunct to help discriminate subsets of ND-BE/LGD from HGD/EAC.ConclusionsWe propose that the maximum utility of this IHC panel of CDX2, p120ctn, c-Myc, and Jagged1 proteins would be to distinguish between LGD and HGD in histologically challenging cases, given the aggressive interventions still used for HGD in many institutions, and hence may aid in the optimal patient management. The results of this initial study are promising, though further validation is needed before this panel can be used clinically, including future randomized prospective studies with larger patient cohorts from diverse locations.Electronic supplementary materialThe online version of this article (doi:10.1186/s13000-016-0473-7) contains supplementary material, which is available to authorized users.

Overview of major molecular alterations during progression from Barrett's esophagus to esophageal adenocarcinoma

“…MYC is another major transcriptional target of β‐catenin. Similar to CCND1, immunochemical staining showed weaker nuclear expression for MYC in BE and low‐grade dysplasia samples compared to HGD and EAC …”

“…Similar to CCND1, immunochemical staining showed weaker nuclear expression for MYC in BE and low-grade dysplasia samples compared to HGD and EAC. 92 Surprisingly, the presence of abnormal ␤-catenin (including loss of membranous staining and the appearance of nuclear staining) in tissue samples of EAC patients correlates with better survival. 84 The reason behind this observation is not clear, but it is consistent with similar observations in colorectal cancer, where obese patients positive for nuclear ␤-catenin had significantly better overall survival, 93 and in medulloblastoma, where the WNT signature molecular subgroup has the best prognosis.…”

Artificial intelligence technique in detection of early esophageal cancer

“…The performance of the system was better than that of the general pathologist and only slightly inferior to that of the experienced pathologist. In addition, there were still some studies using immunohistochemical indicators only[ 43 ] or the characteristics of nuclear DNA structure and organization combined with DNA ploidy analysis[ 44 ] to grade BE dysplasia, but the results were not satisfactory. Therefore, HE stained pathological image features supplemented by relevant immune indicators or other image enhancement techniques may be the main direction of AI-assisted pathological diagnosis in the future.…”

Studying the Role of IMP3 and P53 in Detection of Dysplastic Changes in Barrett's Esophagus

“…Presence of Barrett's esophagus with high-grade dysplasia (HGD) is considered the best predictor for the development of esophageal adenocarcinoma. Six to sixty percent of HGD cases can progress to EAC each year [3] . However, large previous studies confirmed that patients who are diagnosed as BE with low grade dysplasia (LGD) have five times higher risk of development of EAC in comparison to those with non-dysplastic BE (ND-BE) [1] .…”