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Background: The potential involvement of Notch signaling pathway in cell fate decision, tumor heterogeneity and angiogenesis in solid tumors can be explored in colorectal cancer (CRC). This might further help to improve outcomes in CRC. Here, the promoter methylation of Notch receptor gene (Notch2 and Notch3) and their co-expression with its downstream transcription factor Hes1 has been analyzed. Methods: Seventy-two CRC patients were enrolled to study the role of Notch2, Notch3 and Hes1 genes in colorectal cancer. Promoter methylation and mRNA expression in tumor and adjoining normal tissue were assessed by Methylation Specific PCR and quantitative Real time PCR respectively. Statistical correlation was done by using SPSS. Results: We found that Notch2 and Notch3 were hypomethylated in 52/72 (72.22%) and 54/72 (75%) cases respectively. Hypomethylation of Notch 2 and Notch 3 showed significant association with advanced stage (p=0.001) and (p=0.003) and nodal metastasis (p=0.036) and (p=0.012) respectively. Both Notch 2 and Notch 3 showed increased mRNA expression in 49 (68.05%) and 51(70.84%) patients with a fold change of 3.37 and 5.43 respectively. Positive correlation between hypomethylation and expression was observed for both genes. High expression of Hes1 was found in 53(73.61%) of cases which was highly relatable with over expression of notch receptor genes. Upregulation of Notch 2, Notch 3 and Hes1 showed significant association with high grade tumors, advance stage and presence of LN metastasis, additionally Notch 3 and Hes1 showed significant association with distant metastasis. Conclusion: Hypomethylation of Notch 2 and 3 receptors is playing crucial role in regulating the expression of these genes in CRC. Overexpression of Notch 2, Notch 3 and Hes1 are associated with disease progression in CRC.
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INTRODUCTION: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. We analyzed the clinicopathological features, resectability, immunohistochemical markers, and various factors predictive of disease recurrence and survival. MATERIALS AND METHODS: Retrospective analysis of prospectively maintained database of GIST patients managed from 2005 to 2016 was done. Size, site, malignant potential, nuclear pleomorphism, histopathological variety, immunohistochemical markers, type of surgery, and adjuvant imatinib therapy were analyzed. RESULTS: Ninety-two patients with GIST were analyzed. Immunohistochemistry showed positivity for c-kit (82.4%), DOG1 (75%), and PDGFR-α (79%). Among 16 patients with c-kit-negative tumors, 10 patients were positive for DOG1, PDGFR-α, or both. The most common primary site was stomach (44, 47.8%) followed by small bowel (17, 18.5%) and duodenum (14, 15.2%). Of 92 patients, 80 (87%) underwent R0 resection with organ sparing resection in 56 (70%) patients. Seventeen (21.3%) patients showed recurrence at a median follow-up of 6 years. Median and 5-year overall survival (OS) was 36 months (12–120) and 75%, respectively, and 5-year RFS was 81.8%. On univariate analysis, size, mitotic activity, malignant potential, and nuclear pleomorphism were predictors of recurrence. However, on multivariate analysis, only nuclear pleomorphism was significant. CONCLUSIONS: GISTs had a wide spectrum of presentation, and immunohistopathological features with organ sparing resection were conceivable in maximum. Nuclear pleomorphism may be considered as an important variable to predict recurrence in addition to malignant potential of tumors.