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Heba Ahmed Osman,1 Hanaa Nafady-Hego,2 Khalid Ali Nasif,3,4 Heba A Ahmed,5 Ekram Abdel-Rahman Mahmoud,6 Noher Mohamad Abass,7 Amal Rayan,8 Marwa Ahmed Mahmoud,9 Asmaa Nafady10 1Department of Tropical Medicine and Gastroenterology, Qena Faculty of Medicine, South Valley University, Qena, Egypt; 2Department of Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt; 3Department of Clinical Biochemistry, College of Medicine, King Khalid University, Abha, Kingdom of Saudi Arabia; 4Department of Biochemistry, Faculty of Medicine, Minia University, Minia, Egypt; 5Department of Clinical and Chemical Pathology Sohag Faculty of Medicine Sohag University, Sohag, Egypt; 6Department of Medical Microbiology & Immunology, Faculty of Medicine, Sohag University, Sohag, Egypt; 7Department of Internal Medicine, Faculty of Medicine, Sohag University, Sohag, Egypt; 8Department of Clinical Oncology, Faculty of Medicine, Assiut University, Assiut, Egypt; 9Department of Medical Physiology, Faculty of Medicine, Sohag University, Sohag, Egypt; 10Department of Clinical and Chemical Pathology, Qena Faculty of Medicine, South Valley University, Qena, EgyptCorrespondence: Heba Ahmed Osman, Tropical Medicine and Gastroenterology, Qena Faculty of Medicine, South Valley University, Qena, Egypt, Email drheba.saleh@med.svu.edu.eg; hebaahmed198098@yahoo.comIntroduction: HCC is frequently diagnosed late, when only palliative treatment is available. So, we try to use different immunological markers to identify early HCC in patients with unremarkable raised AFP.Methods: This study was conducted on 112 participants divided into two equal groups: Group I, 56 patients with liver cirrhosis and different stages of HCC; Group II, 56 patients with liver cirrhosis. The diagnosis of HCC was based on AASLD guidelines. TNM and BCLC classification systems are used for staging of HCC.Results: A significant reduction in the median percentage of lymphocyte subset (CD3+, CD4+, CD8+, CD19+) and NK cell percentage (CD56+) has been detected in HCC patients (all P < 0.001). In the HCC group the median monocyte subpopulations CD14+ CD16− Classical, CD14++ CD16+ Intermediate, and CD14−+ CD16++ Non-Classical were 11.7, 4.0, and 3.5, respectively, with marked reduction compared with liver cirrhosis group (all P < 0.001). Patients with advanced stages (BCLC C and D) were more likely to have significantly higher median CD33+ than patients with early stages (BCLC A and B) (P = 0.05); also, the median levels of HLA DR+ lymphocytes % in the HCC case group were 21.8 in patients with advanced disease (BCLC C and D) and 13.1 in patients with early stages of the disease (P = 0.04). Patients with late stage (TNM III) were more likely to have significantly higher median CD14+ CD16− Classical monocyte subset, CD36+ HLA DR+, and CD36+ CD16− than patients with early stages (TNM I and II).Conclusion: Patients with HCC with unremarkable raised AFP showed marked reduction in lymphocytes, natural killer cells, and all monocyte subpopulations. In addition, patients with advanced HCC showed increased CD33+ and HLA DR+ lymphocytes %, CD14+ CD16− Classical monocyte subset, CD36+ HLA DR+, and CD36+ CD16− compared with patients with early stages of HCC.Keywords: monocyte subpopulation, lymphocyte subset, hepatocellular carcinoma, Barcelona clinic liver cancer, tumor (T), nodes (N), metastases (M)

Abstract: Background: Survival of patients after curative surgical resection for gastric cancer (GC) remains poor, thus emphasizing the need for better definition of prognostic factors to improve the long-term course of disease. Methods: From 1999 to 2009, 110 patients had curative-intent gastrectomy for adenocarcinoma. Clinicopathological features, Helicobacter pylori infection, dietary habits and lifestyle, and the presence of proinflammatory gene polymorphisms were evaluated. Results: At the end of follow-up, 55 deaths had occurred, 48 of them due to GC, whereas the median overall survival (OS) and disease-free survival (DFS) were 62 and 51 months, respectively. From the Kaplan–Meier analysis and log-rank test, statistically significant differences in OS and DFS were found for tumor site (only for DFS), tumor size, lymph node metastasis ratio (NR), and tumor-node-metastasis stage, but not for age, comorbidity, H. pylori infection, cigarette smoking, and IL1B or TNFA polymorphisms. Multivariable Cox regression analysis revealed NR was an independent prognostic factor for OS and DFS. Cardia tumor and patient age 65 years or older were also independent prognostic factors for OS and DFS. Conclusions: Tumor-related factors remain strongest predictors of survival in GC patients after surgery. Particularly, NR was an effective feature in identifying patients at high risk for adverse outcome. [Copyright &y& Elsevier]

Abstract: Keratins play a major role in several cellular functions. Each tissue type expresses a specific set of keratins. The immense potential of keratins as diagnostic and prognostic markers for different cancers is emerging. Oral cancer is the fifteenth most common cancer worldwide. However, comprehensive information on the profile of keratins in the oral cavity is not available. Several independent reports have identified keratins using antibody based techniques which have pitfalls due to the cross reactivity of the antibodies to this set of very homologous proteins. A few recent proteomic studies have reported the identification of keratins in head and neck cancer. Majority of the studies have used tissues from the head and neck region without specifying subsites. This study reports the analysis of enriched preparations of keratins from cancer of the gingivo buccal complex (GBC) using MS, 2DE, WB, silver staining of 2DE gels and IHC. Our study reveals the absence of K4 and K13 and presence of K14, K16, and K17, in cancers of the GBC and combination of these expression patterns in the cut margins. This report also shows that K13 is glycosylated. This well characterized profile of keratins may have potential to be used in clinics. Biological significance: In recent years the immense potential of keratins as diagnostic and prognostic markers for different cancers is emerging. However, comprehensive information on the profile of keratins in the oral cavity is not available. Several independent reports have identified keratins using only antibody based techniques which have pitfalls due to the cross reactivity of the antibodies to this set of very homologous proteins. This study reports the analysis of enriched preparations of keratins from a subsite of the oral cavity, the gingivo buccal complex (GBC) using mass spectrometry, 2DE, western blotting, silver staining of 2DE gels and IHC. The proteomic analysis shows the absence of K4 and K13 and presence of K14, K16, and K17 in cancers of the GBC and combination of these expression patterns in the cut margins. This well characterized profile of keratins from the gingivo buccal complex provides defined markers which may have potential to be used in the clinics. [Copyright &y& Elsevier]

Background & Aims: Increasing grade of pancreatic intraepithelial neoplasia (PanIN) has been associated with progression to pancreatic ductal adenocarcinoma (PDAC). However, the mechanisms that control progression from PanINs to PDAC are not well understood. We investigated the genetic alterations involved in this process. Methods: Genomic DNA samples from laser-capture microdissected PDACs and adjacent PanIN2 and PanIN3 lesions from 10 patients with pancreatic cancer were analyzed by exome sequencing. Results: Similar numbers of somatic mutations were identified in PanINs and tumors, but the mutational load varied greatly among cases. Ten of the 15 isolated PanINs shared more than 50% of somatic mutations with associated tumors. Mutations common to tumors and clonally related PanIN2 and PanIN3 lesions were identified as genes that could promote carcinogenesis. KRAS and TP53 frequently were altered in PanINs and tumors, but few other recurrently modified genes were detected. Mutations in DNA damage response genes were prevalent in all samples. Genes that encode proteins involved in gap junctions, the actin cytoskeleton, the mitogen-activated protein kinase signaling pathway, axon guidance, and cell-cycle regulation were among the earliest targets of mutagenesis in PanINs that progressed to PDAC. Conclusions: Early stage PanIN2 lesions appear to contain many of the somatic gene alterations required for PDAC development. [Copyright &y& Elsevier]