Glypican-3 (GPC3) is a member of the membrane-bound heparin sulfate proteoglycans. E-cadherin is an adhesive receptor that is believed to act as a tumor suppressor gene. Many studies had investigated E-cadherin expressions in colorectal carcinoma (CRC) while only one study had investigated GPC3 expression in CRC. This study aims to investigate expression of GCP3 and E-cadherin in colorectal mucinous carcinoma (MA) and non-mucinous adenocarcinoma (NMA) using manual tissue microarray technique. Tumor tissue specimens are collected from 75 cases of MC and 75 cases of NMA who underwent radical surgery from Jan 2007 to Jan 2012 at the Gastroenterology Centre, Mansoura University, Egypt. Their clinicopathological parameters and survival data were revised and analyzed using established statistical methodologies. High-density manual tissue microarrays were constructed using modified mechanical pencil tip technique and immunohistochemistry for GPC3 and E-cadherin was done. NMA showed higher expression of GPC3 than MA with no statistically significant relation. NMA showed a significantly higher E-cadherin expression than MA. GPC3 and E-cadherin positivity rates were significantly interrelated in NMA, but not in MA, group. In NMA group, there was no significant relation between either GPC3 or E-cadherin expression and the clinicopathological features. In a univariate analysis, neither GPC3 nor E-cadherin expression showed a significant impact on disease-free survival (DFS) or overall survival (OS). GPC3 and E-cadherin expressions are not independent prognostic factors in CRC. However, expressions of both are significantly interrelated in NMA patients, suggesting an excellent interplay between both, in contrast to MA. Further molecular studies are needed to further explore the relationship between GCP3 and E-cadherin in colorectal carcinogenesis.
Background: There is an increasing interest for Notch signalling pathway and particularly Delta-like ligand 4 (DLL4), a Notch ligand as potential therapeutic target to improve outcome for patients with pancreatic ductal adenocarcinoma (PDAC). Aim: characterize the expression of DLL4 in PDAC and ampullary adenocarcinoma (AA), evaluate their correlation with clinicopathologic features and patients' survival. Materials and Methods: In a retrospective study, using immunohistochemistry, we assessed the expression of DLL4 in 62 cases composed of 39 cases of PDAC and 23 cases of AA undergone Whipple and received adjuvant chemotherapy and radiotherapy. We assessed the expression level of DLL4 both in tumor cells and stromal vascular endothelial cells. The relationships of DLL4 expression with clinico-pathologic parameters and clinical outcome were evaluated.Results: There was no statistically significant relation between clinico-pathological parameters and DLL4 score expression in tumor cells of PDAC cases. However, there was statistically significant relation between DLL4 score expression in tumor cells of AA cases and tumor stage (p= 0.041). Also, there was no statistical significance regarding DLL4 expression in stromal cells in PDAC and AA cases and clinico-pathological parameters. Regarding survival functions for pancreatic & ampullary tumor cases; the median overall survival (OS) was 10 and 22 months for pancreatic (95% CI: 1-45) and ampullary tumors (95% CI: 1-69) respectively. OS for pancreatic and ampullary tumors was higher in cases with low DLL4 expression versus cases with high expressions with no statistically significance (P=0.48 & 0.09 respectively). The median Progression free survival (PFS) was 7 and 17.5 months for pancreatic (95% CI: 0-43) and ampullary tumors (95% CI: 0-96) respectively. PFS was higher in cases with low DLL4 expression rather than cases with high expressions with no statistically significant differences (P=0.52 and 0.19 respectively). Conclusions: High DLL4 expression in cancer cells was associated with worse OS and DFS than low DLL4 expression.
20529 Background: Much progress has been made in the diagnosis and treatment of GIST but the rarity of second neoplasms in association with gastro intestinal tumours (GIST) have rarely been reported. Methods: We present three case reports of breast cancer, Hodgkin's disease and thyroid cancer associated with GIST Results: The first pt, aged 50 underwent left lumpectomy and axillary clearance for infiltrating ductal carcinoma. Estrogen and Progesterone receptors were positive. Adjuvant chemotherapy , radiotherapy and tamoxifen was administered .Three years later patent was operated for a sub mucous nodule in the stomach which was reported as GIST, CD117+ve,CD34 positive and the patient was followed up. The second pt, male aged 50 was operated for a large intrabdominal GIST tumour (16x16cm) arising from the stomach and later on referral found to have a Rt Supraclavicular node with a nodule in the thyroid. He under went total thyroidectomy with functional node dissection for papillary carcinoma. This was followed Radioactive iodine ablation and eltroxin. Three months later he presented with thoraco abdominal metastasis and treatment with Imatnib was begun, but he soon progressed and succumbed to his disease. The third pt, female, with a history of Hodgkin's disease treated with chemotherapy on follow up. Twelve years later the pt was subjected to extensive debulking for pelvic GIST (16cmx15cm).CD117 positve.She was kept on follow up. A ct chest abdomen and pelvis eight months following surgery was unremarkable. Conclusions: Very few cases have been reported in literature regarding association of second tumours with GIST .And no correlation can be made to generate a hypothesis regarding these associations. No significant financial relationships to disclose.
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