Abstract
Simple SummaryDuring bowel cancer screening programs, many diagnostically problematic polyps are removed. The greatest challenge is to distinguish between adenomas with epithelial misplacement and adenomas with early carcinoma, considering the diagnosis affects prognosis and treatment. Our aim was to analyze the expression of extracellular matrix related genes and proteins DCN, EPHA4, FN1, SPARC, SPON2, and SPP1, in 44 biopsies. Differences were observed in most of the analyzed genes and proteins in adenoma with epithelial misplacement in comparison to adenoma with early carcinoma, reflecting inflammatory stromal reaction to traumatisation and misplacement of dysplastic glands in the submucosa in the former, and desmoplastic stromal reaction to true invasion of dysplastic glands in the submucosa in the latter. The observed expression patterns are too complex to be used in diagnostic work, but might contribute to better understanding extracellular matrix changes in colorectal cancerogenesis and help to find new diagnostic markers in the future.Colorectal carcinoma usually evolves gradually, forming a spectrum of lesions, due to accumulation of genetic mutations and epigenetic alterations. Many early lesions are detected since the introduction of screening programs. The greatest challenge is to distinguish between adenomas with epithelial misplacement (AEM) and adenomas with early carcinoma (AEC), considering the diagnosis affects prognosis and treatment. We analyzed the expression of selected extracellular matrix (ECM)-related genes and proteins, and their regulatory microRNAs using RT-qPCR and immunohistochemistry in biopsies from 44 patients. Differences were observed in AEM in comparison to AEC for DCN, EPHA4, FN1, SPON2, and SPP1, reflecting inflammatory stromal reaction to traumatisation and misplacement of dysplastic glands in the submucosa in the former, and desmoplastic stromal reaction to true invasion of dysplastic glands in the submucosa in the latter. Expression of regulatory microRNAs hsa-miR-200c and hsa-miR-146a significantly negatively correlated with the expression of their regulated genes, while significant difference between AEM and AEC was observed only for hsa-miR-29c. The described expression patterns are too complex to be used in diagnostic work, but might contribute to better understanding ECM changes in colorectal carcinoma development, helping to find new markers in the future.
Highlights
Colorectal carcinoma (CRC) is a heterogeneous disease, which usually evolves gradually, forming a spectrum of lesions, due to accumulation of genetic mutations and epigenetic alterations in key growthCancers 2020, 12, 3715; doi:10.3390/cancers12123715 www.mdpi.com/journal/cancersCancers 2020, 12, 3715 regulatory and differentiation genes [1,2,3,4]
True invasion is characterized by severe dysplasia and desmoplastic stromal reaction while in epithelial misplacement, dysplastic glands in the submucosa appear similar to the surface of adenoma and are usually accompanied by lamina propria [7]
The adenomas with early carcinoma (AEC) group consisted of 5 tubulovillous adenomas, 3 tubular adenomas, 1 villous adenoma and 1 tubular adenoma, all with high grade dysplasia and with malignant transformation, shown by invasion of the dysplastic glands in the submucosa
Summary
Colorectal carcinoma (CRC) is a heterogeneous disease, which usually evolves gradually, forming a spectrum of lesions, due to accumulation of genetic mutations and epigenetic alterations in key growthCancers 2020, 12, 3715; doi:10.3390/cancers12123715 www.mdpi.com/journal/cancersCancers 2020, 12, 3715 regulatory and differentiation genes [1,2,3,4]. In the majority of cases, histopathology examination is straightforward, but there is a growing number of cases with ambiguous histopathologic features For this reason, we would need additional histopathologic, immunohistochemical and/or genetic markers to be used in problematic lesions [6,7]. The most challenging task is to distinguish between AEM and AEC In both lesions, dysplastic glands are found in the submucosa, but only in AEC, it is the result of true invasion [7,8]. In AEM, dysplastic glands are present in the submucosa due to traumatization and consequent reparation This is typically a result of intraluminal traumatic injury of the larger polyps due to combination of different factors (narrow, highly motile sigmoid colon, solid fecal material and diverticulosis) [6]. Its characteristic features are hemosiderin depositions and mucus lakes [7]
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