The Studies Of The Expression Of APC,bcl-2 And C-met In Gastric Cancer And Precancerous Lesions And APC Gene Mutations In Gastric Cancer

Gastric cancer(GC) is one of the most common malignant neoplasms in digest systerm worldwide.It is very important to find GC early for the curative effect of GC.The rate of the diagnosis of the early GC is much lower in our country.So it is very important to go a further study of the different change of the molecular and gene in the precancer lesion and GC tissues.It is helpful to determine the molecular marker in the patients at high risk of GC and to improve the diagnosis rate of early GC.Recently GC is thought of multistage and multi-process.Some studies have indicated that oncogene c-met, antioncogene APC and apoptosis inhibiting gene bcl-2 are expressed abnormally in the precancerous lesion and GC tissues.And the gene changes are the early incident in the progress of GC development.There are a little domestic reports and some conclusions are controrersial.So we examined the expressions of c-met,APC and bcl-2 in gastric precancerous lesions and GC tissues and examined for APC gene mutations in GC and adjacent tissues.To discuss the functions of these genes during the development and progression of GC.It will provide the theory base of molecularbiology for the diagnosis of early GC and for gene treatment.The current studies include two parts summarized as follow:Part one: The study on the significance of expression of c-met,APC and bcl-2 in gastric cancer, precancerous lesion and gastric adenoma.Objective: To investigate the role of the expression of APC, bcl-2 and c-met gene in the progress of gastric cancer and the significance of those in the diagnosis of the early gastric cancer.Methods: Applying standard immunohistochemical in 30 cases of human gastric carcinoma(GC),30 cases of intestinal metaplasia (IM),30 dysplasia (Dys) gastric mucosa , 10 gastric adenoma(GA) and 30 normal stomach mucosa.Results:â‘ The positive expression rates of APC in IM, Dys , GA and GC (67.7% , 53.3%,50%and 60%respectively) were significantly lower than those in normal gastric mucosa(90%, P<0.05).The positive rate of APC in moderate and severe Dys(30.8%) were lower than that in mild Dys(70.6%, P<0.05).The positive expression rate of APC in early GC(20%) was significantly lower than that(68%) in progressional GC (P<0.05). The expression rate of APC in GC without lymph node metastasis was higher than those with lymph node metastasis (P<0.05).â‘¡The positive expression rates of bcl-2 in GC (66.7%),IM(43.3%) and Dys(40%)were higher than those in normal gastrica mucosa(6.7%) and GA(30%)(P<0.05). The positive expression rate of bcl-2 in mild Dys (23.5%) was lower than those in GC(66.7%,P<0.05).There was no difference in the positive expression rates between moderate-severe Dys and GC.(P>0.05).The bcl-2 overexpression was significantly related to the histological differentiation degrees(P<0.05) and Lauren type (P<0.05).â‘¢The positive expression rates of c-met in GC(76.7%),IM(63.3%) and Dys(60%) were higher than those in normal gastric mucosa(10%,P<0.05)) and gastric adenoma (40%, P<0.05).The positive expression rate of c-met in moderate and severe IM (84.6%)was higher than those in mild IM(41.2%.P<0.05). The positive expression rate of c-met in moderate and severe Dys(85.7%) was higher than that of in mild Dys(43.8%, P<0.05). The positive expression rate of c-met in early GC(40%) was significantly lower than that(84%) in progressional GC (P<0.05). The expression of c-met gene in GC with well differentiation was higher than that with poor differentiation(P<0.05). The expression of c-met gene in GC with lymph node metastasis was higher than that without lymph node metastasis (P<0.05).Conclusion: The lose of APC or bcl-2 and c-met gene over expression were contributed to the occur and development of GC .To detect the expressions of APC, bcl-2 and c-met gene in moderate and severe Dys may be helpful for diagnosis the early gastric cancer.Part Two:Study of mutations of APC gene in gastric cancer and the matched adjacent tissuesObject:To investigate the role of APC gene mutations in the development and progress of gastric cancer.To investigate weather or not mutations of APC may help to diagnosis the early gastric cancer.Method: We examined mutations of APC gene 15 exon fragments in MCR(mutation cluster region)in gastric cancer and their paired adjacent tissues by reverse-transcription(RT-PCR) followed by DNA sequencing of the PCR products.Results:Of all the 26 cases gastric cancer(GC),19.2% of patients(5 cases) presented mutations in APC,respectively ,and 11.5% of patients(3 cases) presented APC mutations in paired adjacent tissues.There was no significant difference in the mutation rate between the GC tissues and the paired adjacent tissues(P>0.05).The basyl informations of APC mutation were identical in the three GC and their paired adjacent tissues.There was no significant difference in mutation rates among the intestinal metaplasia (IM), dysplasia (Dys) and the else group of the GC adjacent tissues(P>0.05).Of 20 intestinal type GC ,5 cases were founed APC gene mutation(20%),respectively,while one case was founed APC gene mutation in 6 diffuse type GC(16.7%).The mutation rate in intestinal type GC was a little higher than that in diffuse type GC,but there was no significant diference between them(P>0.05).One case was detected APC mutation of 5 early GC(20%), respectively,while 4 cases were founed APC gene mutation of 21 progressive GC(19.0%) . There was no significant diference between them also(P>0.05).Conclusion:APC gene mutation had already been found in the precancerous lesion in adjacent tissues of GC,which was the early event in gastric carcinogenesis.So it may be helpful to find early GC if we detected the APC gne mutation in the precancerous tissues and follow-up the case which had APC mutation.APC gene may play a promotive role in both of the early GC and the progressive GC.APC gene may play a role in the intestinal type GC and the diffuse type GC.