Expression Of β-catenin And APC In Gastric Cancer And Gastric Adenoma

BackgroundWnt gene in 1982 found that as a first priority mouse mammary tumor virus integration sites were identified,and at that time was named Int gene.Subsequently,it found no wings and the Drosophila gene(Wingless) have a high degree of homology, and will be a combination of both called Wnt gene.Wnt gene encoding the Wnt protein,cells can be activated signal transduction pathway,the signal transduction stimulate growth,in different developmental mechanisms,it named the Wnt signaling pathway.Under normal circumstances,the regulation of cellular growth and differentiation;When abnormal activation,it can lead to malignant transformation and tumor cells occurred.Ways to 1996 the relevant members have been identified and cloned.Currently,Wnt way to the overall framework has been basic understanding were Wnt/β-catenin way planar cell polarity ways and Wnt/Ca2+ channels.The Wnt/β-catenin channels called classic Wnt channels,the channels throughβ-cateni nuclear translocation and activation of the transcription activity of target genes.Research shows that the way in tumor occurrence and development. Therefore,we focus on Wnt/β-catenin ways:as a factor of activated Wnt protein and its membrane receptor(Frizzled) combination,will be exported to intracellular signal from intracellular to APC(adenomatous polyposis coli),GSK3(glycogen synthase kinase3) and Axin complex structure changes induced cytosolic ofβ-catenin phosphorylation can occur,rather than phosphorylation ofβ-catenin was not due to protease degradation and accumulate in the cytoplasm,in turn,through its cytoplasm-the nucleus translocation,nuclear transcription factor TCF/LEF(T cell factor/lymphoid enhancer factor) activation and activated Wnt pathway biological effects.Wnt target genes,including the way the cell cycle and apoptosis-related genes (such as c-myc,cyclin D1),growth factors(such as VEGF,gastrin,HGF,c-met),in tumor progression factor(such as MMP7,MMP26,CD44,etc.),transcription factors (such as ITF2) and other target genes(such as COX-2).Therefore,the Wnt pathway on the formation of a variety of tumor play a key role,such as:breast cancer, colorectal cancer,stomach cancer,liver cancer,thyroid cancer,prostate cancer, endometrial cancer,and so on.B-catenin gene is the first identified members of the Wnt in 3 p2.1 from 16 exon composition of exon 3 mutation or deletion→β-catenin degradation blocked.APC gene is related to the occurrence of colon cancer and the tumor suppressor gene,located in 5 q2.1,promotingβ-catenin phosphorylation and degradation,the mutation may occur at any exon to stop the combination ofβ-catenin complex.Numerous studies show that many tumor varying degrees ofβ-catenin and APC gene mutation.Gastric cancer is the most common malignancy of serious harm human health.The incidence of gastric cancer but the exact mechanisms have not yet been fully explained,the early diagnosis of gastric cancer is still the current hot spots.In recent years found that tumors might be due to the deterioration of normal signal transduction interference or damage occurred,resulting in cell growth,division and differentiation out of control.Current areas of concern Wnt signal transduction pathway in the regulation of cellular proliferation,differentiation, motility and morphology,and other aspects play an important role,andβ-catenin and Wnt signaling pathway APC is a key link in abnormal activation.Now found that the incidence of certain tumors,development andβ-catenin expression of the abnormal closely related,but the domestic gastric cancer in the study less. Through the observation ofβ-catenin and APC in gastric carcinoma and adenoma of the expression ofβ-catenin and APC in gastric cancer occurrence and development of the role.It can provide a theoretical basis for further study the role of Wnt pathway in gastric cancer.Adenoma is a benign lesions.It defined as a structure which is made of tubular and(or) villous,and it show clearly the realm of.intraepithelial neoplasia.Adenomas occur in colorectal,can also occur in the small intestine,appendix,stomach, gallbladder,pancreas,etc.WHO classification of tumors epithelial tissue diagnosis of precancerous lesions of the name,definition and standards made some new provisions, proposed a "intraepithelial neoplasia" concept.Precancerous changes in epithelial pathologist has been a concern,precancerous lesions presented by the epithelial cells and structural changes have been given different names such as "dysplasia", "dysplasia","intraepithelial neoplasia Change "can be seen as" dysplasia "synonymous,but dysplasia focused on morphological changes,intraepithelial neoplasia is even more emphasized the evolution of tumor.Intraepithelial neoplasia the scope of a more extensive dysplasia.Dysplasia is usually divided into light, medium,severe 3;intraepithelial neoplasia is divided into low-level and high-level two,low-grade intraepithelial neoplasia refers to the structure and abnormal cytology limited to the second part of epithelium,or light And the moderate degree of dysplasia,high-level intraepithelial neoplasia refers to the structure and abnormal cytology extended to the first half of the epithelial layer and even the whole,or severe dysplasia and carcinoma in situ.Adenoma progress of the cancer incidence rate for its gross type,size and organizational structure of the high-level intraepithelial neoplasia low-level,more progress to cancer.In a sense it that the stomach adenomas gastric cancer is the early event.Through the observation ofβ-catenin and the APC protein in normal gastric mucosa-stomach adenomas-gastric adenocarcinoma of expression, to found in gastric cancer occurrence and development of the role.ObjectiveThis paper MaxVision fast immunohistochemical methods and 30 cases of gastric adenocarcinoma,24 cases of gastric tumors,24 patients with normal gastric mucosa ofβ-catenin and APC protein expression.ResultsⅠ.In normal gastric mucosa ofβ-catenin expression was clear brown staining, positive expression almost all located in the membrane 100%(24/24),the only individual specimens cytoplasm are extremely weak staining(2/24) and no nucleus expression.Gastric cancer ofβ-catenin expression cytoplasm and nucleus increased 100%(30/30),the cell membrane expression varying degrees of reduction.Abnormal expression ofβ-catenin in normal gastric mucosa,stomach adenomas and gastric cancer among the three groups were significantly different.In low-level intraepithelial neoplasia stomach adenomas,β-catenin expression mainly in the cell membrane(14/14);high-level intraepithelial neoplasia gastric stomach adenomas and high differentiated adenocarcinoma,β-catenin ectopic At the same time,expression of gastric cancer cell membrane with about 76.7%(23/30).Ⅱ.24 cases of normal gastric mucosa APC positive in 21 cases,the positive rate was 87.5%;24 cases of stomach adenomas APC positive in 11 cases,the positive rate was 45.8%,30 cases of gastric cancer expression three cases,the positive rate was 10%.The results showed that the normal control group,stomach adenomas,gastric cancer APC positive rate was decreasing trend of normal gastric mucosa,stomach adenomas and positive rate of gastric cancer on February 2,the differences were statistically significant.High-level intraepithelial neoplasia APC positive although lower than the rate of low-grade intraepithelial neoplasia,but the difference was not statistically significant.Ⅲ.In gastric cancer cases,the abnormal expression ofβ-catenin and the negative expression of APC both have nothing to do with gender,age,tumor size and tumor site(P＞0.05).Conclusionⅰ.Normal gastric mucosaβ-catenin protein expression of the membrane, cytoplasm stomach adenomas mainly for the expression of gastric cancer for cytoplasmic/nuclear expression of the abnormal expression rates were 0%,41.7% and 100%,group differences were statistically significant.Among them,high-level intraepithelial neoplasia stomach adenomas and high differentiated adenocarcinoma mainly cytoplasmic expression of poorly differentiated adenocarcinoma cytoplasm,the nucleus were expressed.Tipβ-catenin protein from the cell membrane to the nucleus transfer and is closely related to the occurrence of gastric cancer,gastric cancer is an early event.Among them,high-level intraepithelial neoplasia stomach adenomas and high differentiated adenocarcinoma mainly cytoplasmic expression of poorly differentiated adenocarcinoma cytoplasm,the nucleus were expressed.Tipβ-catenin protein from the cell membrane to the nucleus transfer and is closely related to the occurrence of gastric cancer,gastric cancer is an early event.Low-grade intraepithelial neoplasia stomach adenomas inβ-catenin protein expression in the cell membrane(100%),high-level intraepithelial neoplasia stomach adenomas and high differentiated adenocarcinoma in the cytoplasm ectopic expression rate of 100%,and low differentiated adenocarcinoma were expressed in the cytoplasm and nucleus.Tipβ-catenin protein expression changes to a certain extent,reflect the malignant gastric epithelial tissue level,the high-level intraepithelial neoplasia stomach adenomas to a certain extent,already have some characteristics of gastric cancer. B-catenin protein expression and the incidence of gastric cancer,is closely related to the development,may be an early event in gastric cancer.ⅱ.APC gene in gastric adenoma and carcinoma tissue gastric mucosa were significantly lower than that in gastric precancerous lesions in the APC gene expression has been unusual,we can see that the APC gene in the early stages of gastric cancer is involved in the occurrence of gastric cancer.In the low-level and high-level intraepithelial neoplasia stomach adenomas,APC protein expression was no significant difference,but also suggested that immuno-histochemical methods stomach adenomas of the APC protein products for testing does not have specific,it can not be used alone stomach Early diagnosis of tumor.In the stomach adenomas in the APC gene expression has been unusual,the gene inactivation in the incidence of gastric cancer in the developing stomach adenomas and play an important role in,but in gastric carcinogenesis adenoma in the specific mechanisms still need further study.ⅲ.In normal gastric mucosa-stomach adenomas-gastric adenocarcinoma ofβ-catenin protein expression and negative APC protein expression were significantly correlated,β-catenin protein expression may be related to abnormal protein gene mutation in the APC.Joint detection ofβ-catenin protein and the expression of APC protein may help in the diagnosis of early gastric cancer.ⅲⅰ.β-catenin protein and APC protein are two key factor of Wnt pathway.They have all appeared in the abnormal expression in the stomach adenomas and gastric cancer.It notes Wnt pathway play a certain role in the gastric cancer occurrence and development,but the exact mechanism remains to be further studied.