The development of novel adjuncts to aid in the diagnosis of Epithelial Misplacement

Abstract

Epithelial Misplacement (EM) is a benign phenomenon that occurs within polyps most commonly associated with the sigmoid colon. It is brought about because of the colons convulsive nature and this forces a polyps surface epithelium into its submucosa and also causes bleeding.

This is problematic as the Bowel Cancer Screening Programme (BCSP) uses positive Faecal Occult Blood (FOB) test results to identify patients that require pathological review. As EM polyps bleed, they get selected for assessment and this results in them being sectioned and stained. In these cross sections, submucosal glandular tissue will be found that looks like it has formed due to metastatic mechanisms. This can lead to ambiguous diagnoses that will cause some patients to undergo unnecessary surgery.

It is postulated that this can be prevented if the continuity of the EM samples could be measured. This is because only in the EM cases will the submucosal epithelial tissue remain in continuity with the surface. To test this, volumes representative of 9 samples of cancer and 13 cases of EM were segmented and their number of 26 three dimensional (3D) connected components were recorded. These were used with the 99% confidence limits of the two tailed Mann Whitney U Statistic and tested the null hypothesis that the cancer cases were as connected as the EM samples. In this instance, no significant differences were found and so the benefit of measuring the connectivity of these pathologies is questionable.

It was because of this that Immunohistochemical (IHC) alternatives were considered. It was found that Collagen IV antibody staining correctly differentiated nine samples of EM from ten cases of cancer. The Mann Whitney U Statistic found this to be highly significant, p < 0.001, and future investigations should concentrate on automating this analysis.

Although, Collagen IV provided a good classification it relied upon the subjective assessment of a pathologist. Therefore, the use of epithelial specific IR spectra was also investigated and this enabled the eleven EM and nine cancer cases that were investigated to be accurately classified 80% of the time upon cross validation. The collection of epithelial specific spectra relied upon a novel digital staining technique that has much application within future research.

This study demonstrates that the intermodal registration of complementary modalities is of benefit to the disease classification problem. This technique has potential to be used in the correct identification of EM but more work is required.