| objective:To explore the clinical diagnostic criteria of sessile serrated adenoma (SSA) and reveal the role and regulatory mechanism of canonical Wnt signaling pathways in SSA, and to provide new intervention targets for its prophylaxis and treatment. Method: Retrospectively read the sections of colonic polyps (From Sept.1998to Mar.2011) obtained from Pathological Department of the Affiliated Hospital of Luzhou Medical College and selected262cases of colon polyps specimens, including104Hyperplastic polyp(HP) samples,39SSA samples,34Traditional serrated adenoma(TSA) samples,85Traditional adenoma(TA) samples for analysis, while10normal colonic tissues(NC) were used as control. Histological type of each specimen was confirmed by pathological diagnosis. Serrated polyps (including HP, SSA, TSA) and TA specimens were subjected to HE staining. Expression of β-catenin, Aenomatous polyposis coli (APC), Mutated in colon cancer (MCC) in HPs, SSAs, TASs, CRCs, and NCs were detedcted by immunohistochemical SP method. All statistical tests were performed using SPSS software Version13.0. Data are presented as mean and standard deviation for continuous variables and as proportions for categorical variables. Data were analyzed using one-way ANOVA, followed by Bonferroni test for multiple comparisons, count data was analyzed by chi-square test. Differences were considered significant when P<0.05. Results:(1)There were6112slices of colorectal polyps in total. Among these39SSAs were detected, which accounts for about0.64%of all polyps and9.18%of all serrated lesions.(2)The main identification points of SSAs and HPs:1, Round or oval nucleus of the superficial parts of crypts;2, mitotic activity increases in the middle and upper part of crypts;3, the serrated structure starts at the bottom of the crypts;4, other features of the crypts:branch crypts, flat crypts, inverted crypts;5, other features of mature obstacles cell:goblet cells can be seen at the base of crypts, goblet cells on superficial parts of the expansion and be full of mucus. The differences between TSAs and SSAs are:TSAs were mainly found at left-side location, which were accompanied with dysplasia, stained nuclear, stretched nuclear, layered nuclear, penicillate nuclei and abundant to moderate eosinophilic cytoplasm.(3) In all10normal colonic tissues, expression of β-catenin was clearly evident at cell membrane. However, the abnormal expression of β-catenin was seen in86.7%(26/30) of CRCs,6.5%(2/31) of HPs(left),14.2%(5/35) of HPs(right),48.7%(19/39) of SSAs,31.2%(10/32) of TSAs and57.8%(26/45) of TAs. The frequence of β-catenin nucleus expression in SSAs was higher than that of TAs(X2=11.858,P=0.003). In68HPs, the frequence of β-catenin nucleus expression in the right HPs(14.2%) was significantly higher than that of the left HPs(0%, X2=6.964, P=0.031). In the right HPs, the frequence of β-catenin(C-terminus) membranous, cytoplasmic, nucleus expression (91.4%,8.6%,0%) was significantly different from that of β-catenin(N-terminus)(85.7%,0%,14.3%, X2=8.065, P=0.018). The difference between expression of β-catenin(C-terminus) and β-catenin(N-terminus) was significant in SSAs(X2=8.039, P=0.018), in TSAs(X2=12.705, P=0.002), especially in TAs(X2=22.258, P<0.001). The average cytoplasmic expression score of the APC staining in NCs was94.47±3.57and there was no difference between the left HPs and the NC group(91.39±6.24, P=0.111), The cytoplasmic expression score of APC in SSAs was73.29±5.88, significantly higher than the TAs(31.58±5.56) and the CRCs (24.86±5.21, P<0.001). The average staining score of MCC in the NCs was88.29±4.00. The staining score of MCC in the right HPs(51.25±5.70), SSAs(38.76±5.69), and CRCs(31.17±4.39) was significantly lower than the left side HPs(75.80±5.01) and TAs group (72.73±6.05, P<0.001). Conclusion:(1) The four most important diagnostic features for SSA are:①hyperserration/serration in the lower third of the crypts (with and without branching);②T-and L-shaped crypts above the muscularis mucosae;③inverted crypts (pseudoinvasion) below the muscularis mucosae;④columnar dilatation in the lower third of the crypts(with or without mucus). SSA can be confirmed if there are two or more crypts exhibiting two features out of the four diagnostic features even these crypts are not consecutive.(2) Aberrant activation of Wnt signaling has a role in the development of SSAs. Nuclear accumulation of β-catenin in the right HP may be the early events in the carcinogenesis of SSAs.(3) Different from the traditional adenoma (TA)-carcinoma sequence, activation of Wnt signaling pathway in SSAs may be related with the transportation a distinct of another molecular form of β-catenin into the nuclear.(4) Downregulation of APC expression may not play a major role in the activation of Wnt signaling pathways in SSAs. The loss of MCC expression may contribute to the activation of Wnt signaling pathway. |
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