Expression Of MUC2 MUC5AC Bmi-1 C-Myc MDM2 And Its Significance In Gastric Mucosal Serrated Lesions

Background: Gastric carcinoma (GC) is one of the most common malignancies, account for the second of all of malignancies in our country. At present, early stage diagnosis and early stage therapy is still only one effective treatment to improve the survival rate of Gastric carcinoma's victims.Serrated lesions were a series of correlation lesions being gradually recognized in the research about precancerous lesions of colorectal cancer during the recent 20 years. These lesions were characterized by gland with serrated glandular structure (SGS) in histology manifestation. About 10-15% of sporadic CRCs arise from serrated lesions. At present, the colorectal serrated lesions were known with significant heterogeneity and specific molecular changes showed a continuous pedigree. There have been some reports about serrated lesions appearing in gastric mucosa, but what we lack is systematic and thorough observation and research.Objective: This research is to observe the morphological characteristics of SGS in different groups, the expression of MUC2, MUC5AC, Bmi-1, c-Myc and MDM2. The relationship between SGS of gastric mucosa and the precancerous lesions of gastric carcinoma is discussed.Methods:1 Reserch object1.1 Specimens for observing in histologyWe collected biopsy specimens from the Second Hospital of He Bei Medical University during the period of 1996-2010, which were diagnosed as local protuberant lesions of gastric mucosal by endoscopic examination. Choose the gastric mucosa lesions with SGS, observing the morphological features of SGS and analysis the distribution of SGS in different groups. 1.2 Specimens for immunohistochemicalCollection 25 cases of gastric mucosal inflammation (GMI) with SGS, 53 cases of hyperplastic polyp (HP) with SGS, 31 cases pericancerous mucosa (PCM) with SGS. Collected 15 cases normal gastric mucosa (NGM) and 14 cases of gastric carcinoma (GC) were used as control. In this research, the SGS of gastric mucosal was observed as the specific object.2 Immunohistochemical stainingThe protein expression of MUC2,MUC5AC,Bmi-1,c-Myc,MDM2 were detected with immunohistochemisty S-P two-step. The procession was carried out according to manufacturer's instruction. Hematoxylin staining again,grad alcohol dehydration, dimethyl benzene transparence, neutral gum mounting, observe under light microscope.In this research, when determining the effective of positive immunohistochemistry in the gastric mucosa with SGS, the observed objects were only the glands with SGS.3 Statistical analysisThe experimental data were analyzed with Chi-square test and correlation with statistics software of SPSS13.0 edition, P<0.05 had statistically significance.Results:1 The detection rate of SGS in different groupsThe detection rates of SGS were 17.07% of 615 GMI and 62.30% of 191 HP and 39.46% of 147 PCM. Statistical results show that the detection rates of SGS in HP was significantly higher than GMI and PCM.2 To study the expression of MUC2, MUC5AC in different groups2.1 The positive expression of MUC2 in different groupsThe expression of MUC2 in NGM was negative. The positive expression of MUC2 in all of gastric mucosal lesions with SGS and GC were higher varying degrees. The positive expression of MUC2 in GMI, HP, PCM with SGS and GC were 44.00 %(11/25), 30.18%(16/53), 54.83%(17/31), and 78.57%(11/14) respectively. The positive expression of MUC2 in GMI, HP, PCM with SGS and GC were significantly higher than normal gastric mucosa (NGM)(P<0.05).The positive expression of MUC2 in GMI and HP with SGS was significantly lower than in GC, but It was not significantly different between PCM with SGS and GC(P>0.05).2.2 The expression of MUC5AC in different groupsThe widely positive expression of MUC5AC in the 1/3 of NGM's surface. The positive expression of MUC5AC in all groups of gastric mucosal lesions with SGS and GC were lower than NGM. The positive expression of MUC5AC in GMI, HP, PCM with SGS and GC were 96%(24/25), 96.22%(51/53),0.96%(21/31),and 35.71%(5/14) respectively. The statistical differences were not found among positive expression in GMI, HP,and NGM with SGS(P>0.05).The positive expression rates of MUC5AC in PCM with SGS and GC were significantly lower than normal gastric mucosa(P<0.05).The positive expression in GMI, HP and PCM with SGS were significant higher than GC(P<0.05).2.3 Relationship between MUC2 and MUC5AC in different groupsIn GMI with SGS, the correlation could not be found between the protein expression of MUC2 and MUC5AC. In HP, PCM and GC, the negative correlation could be found between the protein expression of MUC2 and MUC5AC. And in the three lesions the relevance was more and more higher. (r=-0.301,r=-0.438,r=-0.640)3 The positive expression of Bmi-1 in different groupsThe positive expression of Bmi-1 was fewer in NGM 6.67%(1/15).The positive expression of Bmi-1 in GMI,HP,PCM with SGS and GC were 24.00%(6/25),28.30.%(15/53), 45.16%(14/31) and 57.14%(8/14) respectively. The positive expression of Bmi-1 in GC was significantly higher than NGM(P<0.05).The positive expression of Bmi-1 in all groups of gastric mucosal lesions with SGS were not found statistical differences than GC(P>0.05). 4 The positive expression of c-Myc in different groupsThe positive expression rate of c-Myc was 13.33%(2/15) in NGM. The positive expression of c-Myc in all of gastric mucosal lesions with SGS and GC were higher than NGM. The positive expression of c-Myc in GMI, HP, and PCM with SGS and GC were 12.00%(3/25), 13.20%(7/53), 29.30(9/31)%, and57.14%(8/14) respectively.The statistical data shows that the positive expression of c-Myc in GMI, HP and PCM with SGS were not statistical differences than NGM(P>0.05).5 The positive expression of MDM2 in different groupsThe positive expression rate of MDM2 was 20.00 %( 3/15) in NGM. The positvie expression of c-Myc in all of gastric mucosal lesions with SGS and GC were higher than NGM. The positive expression of MDM2 in GMI, HP, and PCM with SGS and GC were 32.00%(8/25),24.53%(13/53), 54.84%(17/31), and 85.71%(12/14) respectively.The positive expression of MDM2 in GMI,HP were not statistical differences than NGM(P>0.05),then in PCM and GC were significant higher than NGM.The positive expression in GMI and HP were significant lower than GC(P<0.05),then the positive expression in PCM was not statistical differences than GC NGM(P>0.05).6 Relationship between Bmi-1 and c-Myc in different groupsThe statistical results showed that correlation was not be found between the positive expression of Bmi-1 and c-Myc in all of groups.7 Relationship between Bmi-1 and MDM2 in different groupsIn GMI,HP and PCM, the positive correlation could be found between the protein expression of Bmi-1 and MDM2. But it was not correlation in GC.Conclusions:1 The positive expression MUC2 protein was higher and MUC5AC was lower in GMI,HP,PCM and GC than NGM,and the positive expression of two genes was negative correlation in HP, PCM and GC.The results suggested that part of SGS was novel expression of mucin which was similar to GC. 2 The positive expression of Bmi-1 in all of the SGS lesions in gastric mucosa was upregulated than NGM, and was not statistical differences than GC.This study demonstrates that the overexpression of Bim-1 was associated with the formation of some SGS.3 The positive expression of MDM2 in GMI and HP with SGS were not statistical differences than NGM, but in PCM was significant higher than NGM.This suggests that the overexpression of MDM2 was associated with the SGS in PCM.4 This study demonstrates that Bmi-1 gene have positive regulation to MDM2 gene in all of SGS lesions.5 In this research, we considered that c-Myc gene has nothing to do with all of SGS in gastric mucosa.