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<p><b>OBJECTIVE</b>To illustrate the role of methylation level of hMLH1 gene promoter in different stages of gastric carcinogenesis by methylation-specific PCR (MSP) detection of samples from paracancerous tissue and gastric cancer tissue.</p><p><b>METHODS</b>Methylation status of hMLH1 gene promoter of 40 patients undergoing radical stomach cancer operation in the Tumor Research Institute of China Medical University between January 2006 and August 2006 was detected by MSP. For each patient, 2 samples were chosen from the cancer site, paracancerous tissues of 1 cm, 3 cm, 5 cm away from the cancer site, separately. One sample was used in pathology examination, and the other in methylation detection.</p><p><b>RESULTS</b>Positive rates of hMLH1 gene promoter methylation in the paracancerous tissues of 1 cm, 3 cm, 5 cm away from the cancer site were 10%(4/40), 12.5%(5/40) and 2.5%(1/40) respectively, which were significantly lower than 32.5%(13/40) in cancer site(all P<0.05). Pathological examination showed precancerous lesions in 23 samples of paracancerous 1 cm and 3 cm tissues and normal tissues in 24 samples of paracancerous 5 cm tissues. Positive rates of hMLH1 gene promoter methylation in the cancer site, paracancerous tissue and normal gastric tissue were 32.5%(13/40), 8.7%(2/23) and 0(0/24) (P<0.01). For cancer tissue penetrated the gastric serosa, 8 out of 14 tissue samples were positive methylation (57.1%), which was significantly higher compared with 5 out of 26 tissue samples without penetration of gastric serosa(19.2%). Positive rate of hMLH1 gene promoter methylation in tissue samples with 7 or more of metastatic lymphatic node number was 61.5%(8/13), which was higher compared to that with less than 7(5/27, 18.5%) (P<0.05). No significant differences of positive rate of hMLH1 gene promoter methylation were found between different tumor gross types, tumor grow pattern, tumor differentiation degree, patient age and sex(all P>0.05).</p><p><b>CONCLUSION</b>Hypermethylation of hMLH1 gene promoter may be associated with the carcinogenesis stages and progression of human gastric cancer.</p>
Subject(s)
Humans , Adaptor Proteins, Signal Transducing , Cell Transformation, Neoplastic , China , DNA Methylation , Disease Progression , MutL Protein Homolog 1 , Nuclear Proteins , Polymerase Chain Reaction , Promoter Regions, Genetic , Stomach NeoplasmsABSTRACT
Objective To analyze and improve Methylation-specific Polymerase Chain Reaction. Methods Methylation state of DAPK in gastric cancer was detected by this improved MSP. Results 100 % of frozen tissues and 24.1% of paraffin-embedded tissues could get either methylated production or unmethylated production. Conclusion Improved MSP is a convenient, sensitive and specific way to screen DNA methylation, especially for frozen tissues, but for paraffin-embedded tissues,it may be unsuitable.
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Objective To review the relationship between histone modifications and gastrointestinal cancer.Methods Literatures on histone modifications and the relationship between histone modifications and gastrointestinal cancer were collected and reviewed.Results Histone modifications played an important role in the establishment of gene silencing during tumorgenesis.DNA methylation and histone modifications might interact with each other and form a complex network to establish and maintain gene silencing.Restoring gene function silenced by epigenetic changes in cancer had the potential of 'normalizing' cancer cells,which was named epigenetic therapy.Epigenetic therapy was very promising in prevention and treatment of gastrointestinal cancer,but many unsolved issues remain which need to be addressed in future studies.Conclusion Histone modifications are associated with the pathogenesis of gastrointestinal cancer.Restoring gene function silenced by epigenetic changes may have a great role in the prevention and treatment of gastrointestinal cancer.
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Objective To investigate the relationship between methylation of tumor suppressor gene and gastric cancer. Methods The literatures in recent years about the concept of methylation, its biological significance and the relationship between DNA methylation/demethylation and gastric cancer were reviewed. The effects of methylation of different tumor suppressor genes on gastric cancer were also analyzed. Results The effect of aberrant methylation on the development and the progression of gastric cancer was still unclear but it was supposed that the inactivation of genes related with cell cycle regulation, mitotic checkpoint, apoptosis, DNA mismatch repair, metastasis suppression and so on might be attributable to the aberrant methylation in gastric cancer. Conclusion Aberrant methylation of tumor suppressor genes plays an important role in the development and progression of gastric cancer. The status of methylation of tumor suppressor genes may be used as a useful molecule marker for diagnosis, assessing metastasis and evaluating prognosis, and demethylation could possibly be a new therapy for gastric cancer.
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Objective To investigate the clinical and pathological characteristics, diagnosis and treatment of gastric cancer with ovarian metastasis. Methods The clinical data of 17 cases of gastric cancer with ovarian metastasis, confirmed by surgery and pathology, were analyzed retrospectively. Results The average age of the patients was 48.41 years, and the first appearance of symptoms and signs often were of metastatic ovarian cancer. The main ultrasonographic findings were either a complex type of mass with both solid and cystic characteristics or only solid, and most of them were accompanied by intraperitoneal fluid accumulation. Bilateral metastatic ovarian cancer was more common(13 cases). The preoperative accurate diagnosis of this disease was difficult, so that the misdiagnostic rate was 64.7% in this series. Operation was done in all the patients, but prognosis was poor. The median survival time was only 11.6 months. Conclusions The prognosis of gastric cancer with ovarian metastasis is poor. It is of importance to inspect the stomach in cases of bilateral ovarian cancer. Radical resection of the primary disease focus together with hysterectomy and bilateral adnexectomy should be performed. Postoperative comprehensive therapy is conducive to improve the prognosis of gastric cancer with ovarian metastasis.