Relationship Of Expression Of HMSH2 And PTEN In Sporadic Colorectal Carcinoma

Objective: The carcinoma of gastrointestinal tract threatens people's health and colorectal carcinoma is the most common malignant tumor in the world. The tumorigenesis of colorectal carcinoma is a complicated process involving in heredity environment and gene mutation.MSI (microsatallite instability, MSI) plays an important role in the tumorigenesis and development of colorectal carcinoma. MSI means repeated sequence loses or gain in DNA genome, which is also called copy error. Up to now, there are 9 mismatch repair genes: hMLH1, hMLH3, hPMS1, hPMS2, hMSH2, hMSH3, hMSH4, hMSH5, hMSH6. Among them hMLH1 and hMSH2 are the most important mismatch repair genes. Their principal role is keeping the integrity and stability of genetic substance and true of duplication. If there genes were defective which result in MSI and probably led to the instability of genome and tumorigenesis of tumor.PTEN is an anti-oncogene, which was discovered and named by three investigations. PTEN is also named MMAC1 or TEP1 (PTEN——phosphates and tensin homolog deleted on chromosome 10, MMAC1——mutated in multide advance cancers, TEP1----TGFβ-regulated and epithelial cell enriched phosphatase), which was first found to possess phosphotase active anti-oncogene by now. Mechanism actions of PTEN were reported by a lot of references. (1) PTEN is direct to make FAK dephosphorylation thus suppressor cell growth. (2) PTEN inhibits PIK dephosphorylation and prevents PIP2 transform PIP3 then which prevents Akt and its downstream gene to restrain carcinoma. (3) PTEN suppress ERK activated MAPK channel to make it unsuffer integrin and growth factor thus suppressor cell growth. When PTEN is loss, MAPK channel is actived and it irritates cell multiplication to lead to carcinoma.42 cases of sporadic colorectal carcinoma, the corresponding proximal adjacent tissues (3cm from the cancer tissue), distal adjacent tissues (from cancer> 10cm) and 15 cases of normal colorectal tissues were analyzed by immunohistochemistry SP, the two-step method to detect the expression of hMSH2 and PTEN. 42 cases of sporadic colorectal carcinoma and the corresponding remote control tissues (from cancer>10cm) were analyzed by Western Blot to detect the expression of hMSH2 and PTEN. To discussion hMSH2 and PTEN expression in sporadic colorectal cancer incidence and development, the loss of hMSH2 and PTEN expression led to the formation of malignant tumors.Methods:1 MaterialThe investigated 42 cases of primarily colorectal cancer was treated by gastrointestinal department of the second hospital of Hebei medical university. We take Sporadic Colorectal Carcinoma (SCC), proximal tumor-adjacent colorectal carcinoma tissues (3cm from the cancer tissue), distal tumor-adjacent colorectal carcinoma tissues (from cancer> 10cm) and normal colorectal tissues. All of them was deviated two shares and one was quickly put in -80℃refrigerator and the other was put in 10% Liquor Formaldehyde, paraffin imbedding, 4μm continuity incise lamella; All of carcinoma tissues was made a definite diagnosis by pathological physicianRabbit anti-human polyclonal antibody of hMSH2 was bought from Biolegend Company and test dense 1:100. PTEN rabbit anti-human polyclonal antibody was bought from Biolegend Company and test dense 1:50. Both of SP immunohistochemistry kit and DAB kit was bought from Zhongshan Biotechnology Company in Beijing.42 cases of sporadic colorectal carcinoma, the corresponding proximal adjacent tissues, distal adjacent tissues and 15 cases of normal colorectal tissues were analyzed by immunohistochemistry SP, the two-step method to detect the expression of hMSH2 and PTEN. 42 cases of sporadic colorectal carcinoma and the corresponding remote control tissues were retrospectively analyzed by Western Blot to detect the expression of hMSH2 and PTEN.2 Making use of the SAS Systerm for Windows v6.12 software carry out statistical treatment; Count information byχ2 test and P<0.05 for the significant differences. To analysis colorectal cancer by non-parametric statistics Spearman ranks in both the expression of hMSH2 and PTEN.Results: 1 the results of immunohistochemistry staining(1)Both loss expression of hMSH2 and PTEN were higher in SCC than in proximal tumor-adjacent colorectal carcinoma tissues, distal tumor-adjacent colorectal carcinoma tissues or normal colorectal tissues. There was no significant correlation of the loss expression of hMSH2 and PTEN in proximal tumor-adjacent colorectal carcinoma tissues, distal tumor-adjacent colorectal carcinoma tissues and normal colorectal tissues (P>0.05). (2)There was no significant correlation between the loss expression of hMSH2 and the types in tumor differentiation, Dukes stage, invasive depth and the lymph node metastasis (P>0.05). (3)There was a negative correlation between the loss expression of the PTEN and the types in tumor differentiation (P<0.05). There was a positive correlation between the loss expression of the PTEN and the types in Dukes stage, invasive depth and in lymph node metastasis (P<0.05). (4)The loss expression of hMSH2 wasn't significant correlation in age, gender, tumor position, carcinoma tissues type and general types of carcinoma, so does PTEN (P>0.05).2 The results of Western blotComparing to the corresponding remote control tissues (More than 10 cm away from the margin of cancinoma),there were 25 cases (59.52%) with lower expression of hMSH2 protein in colorectal carcinoma and 19 cases (45.24%) with lower expression of PTEN protein in colorectal carcinoma.3 There was a positive correlation between of the hMSH2 and PTEN gene products in sporadic colorectal carcinoma (P <0.05). The expression of the hMSH2 and PTEN gene products mostly were loss or lower of expression in sporadic colorectal carcinoma.Conclusion: (1) PTEN and hMSH2 were loss of expression in sporadic colorectal cancer. (2)There was a correlation of sporadic colorectal carcinoma displaying PTEN with specially clinical and pathological feature. (3) There was a positive correlation between of the hMSH2 and PTEN gene products in Sporadic Colorectal Carcinoma. (4) In sporadic colorectal cancer occurred and development, mismatch repair protein, the loss expression of hMSH2 protein associated with reduced PTEN, tumor suppressor gene lead to inactivation, Both participated in sporadic colorectal cancer incidence, development and led to the formation of malignant tumors.