Relationship Of Expression Of HMSH2 And PTEN In Sporadic Gastric Carcinoma

Objective: Gastric cancer is one of the common malignancies. In China gastric cancer is the top one in all kinds of malignancies, the average mortality rate is 25.53 in every 10, 000 people, and there is an increasing tendency year after year. A large number of experiments demonstrated that most of the coding protein of cancer gene and cancer suppressor gene participate in the conducting path within the cells. It is the activation of cancer gene and inactivation of cancer suppressor gene that cause the occurrence and development of tumors. It involves much alteration of cancer gene and cancer suppressor gene during the process of occurrence and development of gastric cancer. Research on alteration of related cancer gene and cancer suppressor gene will help deepen the understanding of biological essence of gastric cancer and investigate the occurrence of gastric cancer, developing mechanism and provide theoretical basis for guiding the clinical treatment.Mismatch repair gene is a kind of conservative gene during the process of biological evolution, possessing the abilities of restoring basic group mismatch, increasing the fidelity of DNA reproducing, maintaining the stability of gene group, reducing the function of spontaneous mutation. hMSH2 is the first separated human MMR gene, it was cloned by Fishel and others in 1993. Research has shown that hMSH2 has a close relationship with the occurrence of gastric cancer. PTEN (phosphatase and tensin homology deleted on chromosome ten,PTEN)is a newly-found cancer suppressor gene in 1997, it is in 10q23.3, its transcription product is 515kb mRNA, and it is the first found cancer suppressor gene with APA. The present research demonstrates that the realization of PTEN suppression on cancer depends on activity of phosphatase. Research of Yang and others proves that PTEN plays an important role in the process of occurrence and development of gastric cancer. Some research has shown that hMSH2 causes tumors by increasing mutation rate of cancer gene and caner suppressor gene. Whether hMSH2 causes tumors by increasing PTEN mutation and the relativity between hMSH2 and PTEN needs further studies.To investigate the protein expression of hMSH2 and PTEN in gastric carcinoma in this experiment, Proximal tumor- adjace nt gastric carcinoma tissues (Cancer 3 cm distance), Distal tumor-adjacent gastric carcinoma tissues (More than 10 cm away from cancer) and normal gastric tissues(non-cancer resected tissues in trauma, polypus and ulcer and need operation is called normal gastric tissues). And examine the relationships between the expression of hMSH2 and PTEN in gastric cancer and clinicopathologic characteristics, and attempt to seek the best way of diagnosis, evaluating pernicious degree, metastasis potentials and predict the possibilities after cure in gastric cancer.Methods:1. Forty two cases of gastric carcinoma, Proximal tumor- adjacent gastric carcinoma tissues, Distal tumor-adjacent gastric carcinoma tissues and fifteen cases of normal gastric tissues were retrospectively analyzed using SP immunohistochemical method and Western blot with the two Rabbit anti-human polyclonal antibody of hMSH2 and PTEN gene products.2. Adopting SAS6.12 statistics software to process the data, and check the results withχ2, P<0.05 difference means marked significance. Analyze the relation between hMSH2 and PTEN in gastric tissues by using Spearman correlation by rank nonparametric statistics.Results:1. Using immunohistochemical method to investigate the expression of hMSH2 and PTEN:1.1 The expression of hMSH2 and PTEN in gastric carcinoma, Proximal tumor-adjacent and Distal tumor-adjacent gastric carcinoma tissues:hMSH2 and PTEN in gastric carcinoma tissues mainly express in nucleolus and cytoplasm. The loss rate of expression of hMSH2 in carcinoma tissues is 54.76%(23/42), 19.05%(8/42)in Proximal tumor-adjacent ,and14.29%(6/42)in Distal tumor-adjacent gastric carcinoma tissues, and 0.00%(0/15)in normal ones. Loss rate of expression of hMSH2 in gastric cancer is higher than Proximal tumor-adjacent gastric carcinoma tissues, Distal tumor-adjacent gastric carcinoma tissues and normal gastric tissues (P <0.05);and there was no significant correlation proximal tumor-adjacent gastric carcinoma tissues, distal tumor-adjacent gastric carcinoma tissues and normal gastric tissues (P>0.05).The loss rate of expression of PTEN in carcinoma tissues is 61.90%(26/42), 23.81%(10/42)in Proximal tumor-adjacent ,and 16.67%(7/42)in Distal tumor-adjacent gastric carcinoma tissues, and 20.00%(3/15)in normal tissues. Loss rate of expression of PTEN in gastric cancer is higher than Proximal tumor-adjacent gastric carcinoma tissues, Distal tumor-adjacent gastric carcinoma tissues and normal gastric tissues (P <0.05);And there was no significant correlation proximal tumor- adjacent gastric carcinoma tissues, distal tumor-adjacent gastric carcinoma tissues and normal gastric tissues (P>0.05).1.2 The relation between expression of hMSH2 and PTEN and types of pathology in clinicThere is no significant relation between expression loss of hMSH2 and age, gender, position of the tumors, degree of differentiation in tumors, serosa invasion, TNM staging, and shift of lymphaden of the patients (P>0.05).There is no significant relation between expression loss of PTEN and age, gender, position of the tumors in the patients (P>0.05), but negative correlation with the degree of splitting of tumors (rs=-0.707317P <0.05) and positive correlation with TNM staging, invasive depth, and shift of lymphaden (rs=0.748157,rs=0.97958,rs=0.850255,rs=0.877482P <0.05), the higher the differentiation is, the lower rate of expression of PTEN, and a higher rate in serosa invasion,Ⅲ+Ⅳperiod of TNM staging, shift of lymphaden.2.Checking results of Western BlotProtein molecular weight ofβ-actin, hMSH2 and PTEN are respectively 42KD, 110KD and 55kD, masculine strip will appear in 42KD, 110KD and 55kD after Western crossing- breeding. Adopting gelatin imaging analysis system to semi-quantitative analysis the crossing-breeding strips, and the contents of protein will be indicated by IOD. Every timeβ-actin will be tested when testing protein, and make quantitative analysis for the hMSH2 and PTEN. Compared with Distal tumor-adjacent gastric carcinoma tissues, hMSH2 in 42 cases of gastric carcinoma has a low expression, and the rate is 50.00%,PTEN has 17 cases of low expression and the rate is 40.48%.3. Interraltion between hMSH2 and PTENhMSH2 and PTEN is positive correlated in gastric cancer(rs=0.938012 in immunity group testing,rs=0.870675P <0.05 in protein marking testing. There is a decreasing expression in losses of expression of mismatch repair gene and hMSH2Conclusion:(1) Checking results of immunohistochemical and Western blot are accordant, hMSH2 and PTEN in sporadic gastric cancer with the increasing loss rate of expression, both in the expression of sporadic gastric cancer positive rates were higher than the proximal gastric cancer organizations and adjacent tissues, adjacent distal and normal gastric tissues.(2) There is no interrelation between the expression of hMSH2 in the gastric tissues and its pathological features; (3) There is no interrelation between the expression of PTEN and its pathological features: the expression loss rate of PTEN is low in highly-split tumors in the gastric tissues, while it is high in gastric tissues ofⅢ+Ⅳof TNM staging, shift of lymphaden, serosa invasion. (4) In sporadic gastric cancer occurred in the course of development mismatch repair protein hMSH2 expression of PTEN protein deficiencies associated with reduced expression. HMSH2 and PTEN joint detection in the diagnosis of gastric cancer, malignant tumors, and metastatic potential assessment is of important significance. As the associative form molecular biological checking index of metastasized gastric cancer, prognosis and therapeutic schedule, to those high expression of the patients, we can give more active targeted treatment.