Abstract
Background: Colorectal cancers are one of the leading causes of cancer related morbidity and mortality worldwide. In Egypt was 4% in the year 2012 ranking as the sixth cancer in Egypt and representing 53% of GI malignancy. It is obvious that there is no single determining factor for the process of carcinogenesis or spread of colorectal carcinoma. There are many proposed contributing factors, including disturbances in Epithelial-Mesenchymal Transition (EMT) and loss of regulation of adhesion molecules and polarity proteins. Cal-cium/calmodulin-dependent serine protein kinase (CASK) belongs to the Membrane-Associated Guanylate Kinase (MAGUK) family. The role of CASK in Colorectal cancer hasn't been yet fully understood.
Aim of Study: To evaluate the expression of Calci-um/calmodulin-dependent serine protein kinase (CASK) in non-mucinous colorectal adenocarcinoma and to evaluate its correlation with variable clinicopathological factors.
Material and Methods: It is retrospective descriptive study is conducted in the Department of Pathology, Faculty of Medicine, Suez Canal University Teaching Hospital. It include 42 archived paraffin blocks of non-mucinous colorectal adenocarcinoma of patients who underwent surgical excision without previous chemotherapy or radiation, 15 adenomatous polyps and 5 normal mucosa samples. The clinical and path-ological data of studied patients are taken from medical records, pathology referral reports and pathology reports. Patients with incomplete data excluded from the study. Re-viewing the data of survival from the archived registry files at department of Oncology, Suez Canal University Teaching Hospital. Sections cut into 5um thick sections and mounted on positive charged slides for immunohistochemical staining using CASK Antibody (S56A-50): Mouse Monoclonal, Novus Biologicals, Catalogue no. NBP1-47648. Staining intensity graded according to the Allred score on a 0-3 scale.
Data Analysis: The relation between CASK antibody staining intensity in the studied biopsies and other clinico-pathological parameters including (age, gender, histopatho-logical tumor features) was evaluated using Pearson's x2 test. The level of statistical significance (p-value) was set at Results: The study revealed that CASK protein had mainly cytoplasmic and cytoplasmic-membranous pattern of expres-sion. The CASK protein was overexpressed in the majority of CRC samples with 85.7% of cases showing moderate to strong expression, while only 14.3% of cases displayed minimal faint expression. On the other hand, CASK expression was low in the majority (53.3%) of adenoma samples. Addi-tionally, adenomas with high grade dysplasia showed stronger staining intensity for CASK protein and higher percentage of positive cases than the ones with low grade dysplasia by IHC. As regard to the association between CASK protein overex-pression and clinicopathological prognostic factors we found that CASK demonstrated significantly higher expression in tumor samples with early stages (I/II) rather than advanced stage (III/IV). Low grade tumors showed higher percentage of positive cases and stronger intensity of staining for CASK protein than high grade tumors. Expression of CASK protein showed no statistically significant correlation with patients' gender or age respectively. There was also no significant correlation with tumor site, gross tumor size, histologic tumor border configuration, lymphovascular invasion or distant metastasis.
Conclusion: CASK protein was overexpressed in the majority of non-mucinous colorectal adenocarcinoma (CRC) cases with mainly cytoplasmic and cytoplasmic-membranous localization. However, its expression was significantly less in adenomas with a possible association with the grade of dysplasia; giving positive pattern in highly dysplastic cases suggesting a role in the progression of adenomas into carci-nomas. CASK overexpression also associated with both TNM stage of tumors and their histologic grade. CASK was signif-icantly overexpressed in early stage and low grade tumors rather than tumors with advanced stage and higher histological grades. This suggests that CASK protein is a good prognostic factor and might contribute in tumor confinement and local-ization.