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1 colorectal serrated lesions of RUNX3 expression and gene polymorphism observational studies ; 2 serrated colorectal adenoma lint pathological and immunohistochemical characteristics
Author: WangLin
Tutor: WangLuPing
School: Shanxi Medical
Course: Pathology and Pathophysiology
Keywords: Serrated lesions Serrated adenomas Hyperplastic polyps Runx3 transcription factor Filiform serrated adenoma Non-Filiform serrated adenoma Hyperplasia
CLC: R735.3
Type: Master's thesis
Year: 2011
Downloads: 59
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Abstract
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[Background and Objective]Serrated lesions are a group of colorectal adenoma/polyps characterized morphologically by a serrated architecture of the crypt epithelium.Because of their malignant potential, serrated lesions become Research focus and get more attention by clinical Pathologist in recent years.The lesions include hyperplastic polyps(HPs),sessile serrated adenoma/ polyp (SSA/P) and traditional serrated adenoma(TSA) in WHO(2010).TSA and SSA have malignant potential,and different types of HPs also has similar genetic changes like TSA and SSA. Runt-related transcription factor 3 (Runx3) is considered to be a tumor suppressor gene, and have been found that there are RUNX3 gene abnormalities in variety human tumors in recent years. Studies have found that Runx3 is more closely related with human digestive system tumors, But the effection of RUNX3 gene in serrated lesions is not clear.RUNX3 is located on human chromosome 1p36.1,mainly express in gastrointestinal epithelium cells, blood cells, mesenchymal, nerve cells, etc. Research showed RUNX3 could inhibit growth of tumors by regulate cell cycle and induce apoptosis of tumor cell. In this study,the immunohistochemical expression and genetic polymorphism analysis of RUNX3 were observed in serrated lesions, the relationship between them were discussed, and the effection of RUNX3 in serrated pathway were explored.[Methods]A total of 5347 cases of colorectal polyps from five hospitals during a five-year period were retrospectively reviewed. The serrated lesions were classified based on WHO standards and literature. Amongst 5347 colorectal polyps studied,258 cases of serrated lesions were found. Amongst 258 cases of serrated lesions,32 cases of TSA, 8 cases of SSA/P and 25 cases of HP were selected. 25 cases of TA, 25 cases of normal colorectal tissues and 20cases of invasive adenocarcinoma were selected as the controls.All tissue sections were stainned using RUNX3 antibody by immunohistochemical methods.Besides, 50 cases of SA (including 40 cases of SA and 10 cases of SSA/P) and 20 cases of normal colorectal tissues were selected as the controls.Polymorphisms of RUNX3(rs2236851,C/T ) were genotyped by PCR-SSP. The relationship between immunohistochemical expression and genetic polymorphism were explored by IPP methods.[Results]The positive rate of RUNX3 in TSA,SSA and CRC were lower than in normal group.There were significant differences between the TSA,SSA,CRC and normal group.The significant differences also were observed between SSA,CRC and TA.The study of RUNX3 (rs2236851,C/T) polymorphism and the semi-quantitative analysis using IPP software was showed that the frequency of T allele was significantly higher in serrated adenoma(SA) than the normal control group. The RUNX3(rs2236851,C/T) was closely related with SA and the immunohistochemical expression of RUNX3 was lower in SA with TC genotype.[Conclusions]1. Immunohistochemistry expression results showed that the positive rate of RUNX3 expression is reduced in serrated lesions.It was a necessary events for SA changing into malignant lesions.2. The results of RUNX3 genetic polymorphism analysis suggest that RUNX3 (rs2236851, C / T) was closely related with the SA, the expression of RUNX3 in SA (TC genotype) was reduced. [Background and Objective]Serrated lesions are a heterogeneous group of lesions characterized morphologically by a serrated architecture of the epithelial compartment.The lesions include hyperplastic polyps(HPs),sessile serrated adenoma/ polyp (SSA/P) and traditional serrated adenoma(TSA) in WHO(2010). according to the type of mucus, HPs were divided into microvesicula HP (MVHP), goblet cellric HP (GCHP) and mucin poor HP ( MPHP). And according to cell atypia, the SSA/P were divided into SSA/P with dysplasia and SSA/P without dysplasia.Some studies reported an unusual type of TSA with long filiform projections lined by neoplastic epithelium with a serrated contour. These lesions were called Filiform Serrated Adenoma (FSA) in WHO( 2010). At present, domestic and international research with FSA is uncommon and the knowledge about these lesions was little understanding among clinical physicians and pathologists. Most of the pathological and clinical physicians to understand it even less.Therefore, this study discusses the clinical and pathological features of FSA and explore the immunohistochemical chang. Aim to help clinical pathologists enhanced understanding of FSA and to improve the management of patients.[Methods]A total of 5347 cases of colorectal polyps/adenomas from five regional hospitals in five years were retrospectively reviewed and 18 cases of FSA were selected. 20 cases of NFSA(including 15 cases TSA and 5 cases of SSA/P),20 cases of HP and 20 cases of VTA were randomly selected as control group. The clinical pathologic feature of FSA were observed.The expression of Ki-67, p53, CK7,CK20, CDX2, beta-catenin and RUNX3 in FSA,NFSA,HP and VTA were compared by immunohistochemical stain.[Results]Observation of clinical feature showed that FSA account for 0.34% of 5347 colorectal polyps/adenomas and account for 6.98% of 258 serrated lesions.FSA was tend to occur in older adults, and showed a strong predilection for developing in the left colon, especially the rectum. Observation of pathological features showed that FSA with long filiform projections lined by neoplastic epithelium with a serrated contour. The filiform projections of FSA were longer than the villi present in typical VTA .Marked stromal edema was present and the "bulb"-like change was showed in swelling of Severe cases. There was statistically significant difference between FSA and NFSA in the degree of dysphasia(p<0.05). The expression of Ki-67,p53,RUNX3 showed significant difference among FSA ,NFSA,HP and VTA (P<0.05); while the difference among expression ofCK7,CK20,CDX2 and beta-catenin in FSA ,NFSA,HP and VTA were not observed (P>0.05).[Conclusions]1. Observation showed that FSA is an uncommon type of serrated adenoma, shows a strong predilection located in the left colon,especially in rectum.2. Pathological observation results show that FSA has long filiform projections lined by neoplastic epithelium with a serrated contour unlike traditionalSA,.3. Immunohistochemical results suggest that FSA may has higher proliferation activity and higher malignant transformation potential.
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