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Objective To analyze the changes of Survivin,MSH6 and MSH2 expression in colorectal cancer and explore their relationship with clinical and pathological parameters.Methods 197 cases of colorectal adenocarcinoma and 20 cases of inflammatory intestinal mucosa were detected by immunohistochemistry with Survivin,MSH6 and MSH2,and the correlation between Survivin,MSH6 and MSH2 expression was analyzed.Results In the control group of 20 cases with inflammatory non-tumor intestinal mucosa,the positive expression rate of MSH2,MSH6,Survivin were 95％,95％,10％,respectively.While the positive expression rate of MSH2,MSH6,Survivin were 88.3％,74.1％ and 84.3％ in 197 cases of colorectal cancer.Survivin positive expression rate in colorectal cancer group was significantly higher than that in inflammatory control group (P ＜ 0.05).Survivin expression was correlated with invasion depth and lymph node metastasis in colorectal cancer tissue (P ＜ 0.05),but not with gender,age,tumor size,gross type or degree of differentiation (P ＞ 0.05).MSH2 expression was correlated with tumor size and lymph node metastasis (P ＜ 0.05),but not with gender,age,gross type,depth of infiltration and degree of differentiation (P ＞ 0.05).MSH6 expression was related to gender and lymph node metastasis (P ＜ 0.05),but not to age,tumor size,gross type,infiltration depth and differentiation (P ＞ 0.05).Colorectal cancer tissues showed positive correlation between MSH6 and MSH2 (r =0.326,P ＜ 0.01),positive correlation between MSH2 and Survivin positive expression (r =0.277,P ＜ 0.01),and positive correlation between MSH6 and Survivin positive expression (r =0.435,P ＜ 0.01).Conclusions The positive expression rate of Survivin in colorectal cancer is high.MSH2,MSH6 and Survivin in colorectal cancer play an important role in the development and progression of colorectal cancer,and can provide evidence for the detection of these three factors,including metastasis risk,prognosis assessment and clinical treatment.In particular,Survivin gene may provide evidence for gene therapy.
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Objective To explore the expression and clinical significance of mismatch repair (MMR)protein and MLH1 promoter methylation testing in endometrial cancer(EC). Methods A total of 420 cases with EC diagnosed by the surgical pathology examination from the Department of Pathology of PLA General Hospital, MLH1,MSH2,MSH6 and PMS2 protein in EC were detected by immunohistochemistry and methylation-specific multiplex ligation-dependent probe amplification(MS-MLPA) testing. Results (1)Of the 420 tumor cases, the total expression loss rate of MMR protein was 34.5%(145/420), the expression loss rates of MLH1,MSH2,MSH6 and PMS2 protein were respectively 17.1%(72/420), 8.1% (34/420), 7.4%(31/420), 26.2%(110/420)and loss rates of MLH1 and PMS2,MSH2 and MSH6 were 16.7%(70/420), 6.2%(26/420). When there was a loss of MMR protein expression, any one or more protein expression deletions in MLH1, PMS2, MSH2 and MSH6, it could be Lynch syndrome related endometrial carcinoma(LS-EC). The expression loss rate of MMR protein in the poorly differentiated endometrioid adenocarcinoma was higher than that in the well differentiated endometrioid adenocarcinoma(P<0.05).(2) The expression loss rate of MMR and PMS2 protein had statistically significant between the endometrioid adenocarcinoma and non-endometrioid adenocarcinoma(P<0.01). The expression loss rate of MSH2 protein had statistically significant in the stage Ⅲ(P<0.01). Moreover, there were also significant differences in depth of myometrial invasion and lymph node metastasis between the expression loss rate of MMR protein (P<0.05).(3)The expression loss rate of MLH1 protein was 72 cases and 57 cases had MLH1 promoter methylation testing(excluding those who were not qualified for DNA testing). The positive rate was 47.4% (27/57). Therefore, these patients were sporadic endometrial cancer, not non-LS-EC. Conclusions MMR protein may be play an important role in the development of endometrial cancer and be indicated poor prognosis. Immunohistochemical staining and MLH1 promoter methylation detection may be play an important role in the screening of the LS-EC.
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Objective To investigate the reversal effect of hMSH2 small interference RNA(siRNA) on chemo-resistance of ovarian carcinoma cell line OC3/TAX300,explore the clinical significance.Methods The specific hMSH2 siRNA (experimental group) and non-specific hMSH2 siRNA (negative control group) was designed,synthesized and transfected into ovarian carcinoma cell line OC3/TAX300.The expression mRNA and protein levels of hMSH2 were detected by real-time reverse transcription (RT)-PCR and western blot.The cell proliferation was detected by methyl thiazolyl tetrazolium(MTT) method after 12,24,48,72 hours of 2 μg/ml taxol,the apoptosis rate after 24,48 hours of 2 μg/ml taxol was analyzed by flow cytometry.Morphological changes and ultramicrostructure of cells after 48 hours of 2 μg/ml taxol were observed with transmission electron microscope.Results (1) The mRNA levels of hMSH2 were 0.004 ± 0.000,0.053 ±0.006 and 0.057 ± 0.012 in experimental group,negative control group and non-infected group,respectively.The protein levels of hMSH2 were 0.19 ± 0.04,1.00 ± 0.07 and 0.95 ± 0.03 in experimental group,negative control group and non-infected group,respectively.(2) Compared with the noninfected group and the negative control group.The cell proliferation was effectively inhibited after 12,24,48,72 hours of 2 μg/ml taxol(P ＜0.05).The cell cycle was arrested at G2/M phase,the apoptotic rate was significantly increased after 24,48 hours of 2 μg/ml taxol (P ＜ 0.05).The experimental group after 48 hours of 2 μg/ml taxol was found to have more visible cell shrinkage,more serious chromatin margination,nucleus condensation,fragmentation and apoptotic body formation,nucleolus disappeared,markedly swollen mitochondria,mitochondrial cristae disappeared and other signs of apoptosis.While the nucleus was located in the cells of the central and nucleolus is clear,only mild chromatin pyknosis and marginalized,mild swelling of mitochondria in the control group and blank group.Conclusion siRNA targeting hMSH2 may reverse the chemo-resistance of ovarian carcinoma cell line OC3/TAX300 and may become a treatment or a new direction in the adjuvant therapy of ovarian cancer.
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OBJECTIVE: This study aimed to investigate the expression of the MSH2 DNA repair protein in head and neck squamous cell carcinoma (HNSCC) in order to analyze its association with clinicopathologic factors and overall survival of patients. MATERIAL AND METHODS: Clinical data and primary lesions of HNSSC were collected from 55 patients who underwent surgical resection with postoperative radiotherapy in Montes Claros, state of Minas Gerais, Brazil, between 2000 and 2008. Immunohistochemical reactions were performed to analyze MSH2 protein expression. RESULTS: Bivariate analysis showed no significant correlation or association between MSH2 expression and clinicopathologic parameters by Mann-Whitney and Kruskal-Wallis tests. Patients with locoregional metastatic disease (OR=4.949, p<0.001) and lower MSH2 immunohistochemical expressions (OR=2.943, p=0.032) presented poorer survival for HNSCC by Cox regression models. CONCLUSIONS: Our data demonstrated that lower MSH2 expression might contribute to a higher clinic aggressiveness of HNSCC by promoting an unfavorable outcome. .