The Diagnostic Value of Cadherin 17 and CDX2 Expression as Immunohistochemical Markers in Colorectal Adenocarcinoma.

BACKGROUND: Colorectal cancer is a major cause of morbidity and mortality throughout the world. Although the diagnosis of colorectal cancer is straightforward in primary site, yet it may represent a diagnostic problem in metastatic tumor of unknown primary origin. Hence, immunohistochemical analysis in combination with morphologic assessment and correlation with clinical data becomes crucial, because it is important to specify the primary site of metastasis since some specific tumor types may respond well to targeted molecular therapies. Therefore, establishment of reliable diagnostic markers that confirm or rule out colorectal origin is mandatory. AIM: To study the expression of cadherin 17 and CDX2 in colorectal carcinoma and to evaluate their diagnostic roles in identifying metastatic colonic from non-colonic adenocarcinomas in cancer of unknown primary site. DESIGN AND METHODS: This retrospective study included 65 cases of adenocarcinomas: 35 cases of colorectal adenocarcinoma (primary or metastatic) and 30 cases of non-colorectal adenocarcinoma. They were retrieved from the archives of Pathology Department of Ain Shams University and Ain Shams University Specialized Hospitals during the period from 2010 to 2015. Immunohistochemical study was performed using cadherin 17 and CDX2 antibodies. RESULTS: The sensitivity and specificity of CDX2 and cadherin 17 are 97.1% and 53.3% and 100% and 50% in detecting colonic adenocarcinoma respectively. The PPV, NPV, and overall accuracy of CDX2 versus cadherin 17 were 70.8%, 94.1%, and 76.9% versus 70%, 100%, and 76.9% respectively. CONCLUSION: Cadherin 17 is a more sensitive marker than CDX2 in diagnosis of carcinoma of unknown primary site especially when colorectal carcinoma is suspected.

Prognostic significance of HLA EMR8-5 immunohistochemically analyzed expression in osteosarcoma.

BACKGROUND: Defects in Human Leukocyte Antigen (HLA) class I antigen expression and/or function in tumor cells have been extensively investigated, because of their potential role in the escape of tumor cells from T cell recognition and destruction. The researchers evaluated HLA class I expression in tumor tissue as a prognostic factor in osteosarcoma patients and as a predictor of their survival. This retrospective cohort study was conducted at the pathology laboratory of Ain Shams University Hospital, and Ain Shams University Specialized Hospital during the period between January 2009 and January 2012. METHODS: The researchers investigated HLA class I expression in primary osteosarcoma by immunohistochemistry using EMR8-5 mAbs. Furthermore, researchers evaluated the correlation between HLA class I expression and the clinicopathological status and outcome in formalin fixed paraffin embedded tissues from thirty six (36) patients with osteosarcoma. RESULTS: A high expression of HLA class I was detected in 18 (50) % of tumor samples examined; while tumors with low or negative expression represented 9 (25%) cases each. Data indicate that the overall survival rate of patients with tumors highly expressing HLA class I was significantly higher than those with low or negative expression. CONCLUSION: Down-regulation of class I antigen expression is associated with features of aggressive disease and a poorer prognosis. Therefore, it is imperative to identify HLA as a prognostic factor at the time of diagnosis to detect chemotherapy-resistant tumors and to generate a modified treatment regimen. VIRTUAL SLIDES: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1159334857109547.

Implication of protein kinase R gene quantification in hepatitis C virus genotype 4 induced hepatocarcinogenesis.

BACKGROUND: Protein kinase RNA (PKR-regulated) is a double-stranded RNA activated protein kinase whose expression is induced by interferon. The role of PKR in cell growth regulation is controversial, with some studies supporting a tumour suppressor function and others suggesting a growth-promoting role. However, it is possible that the function of PKR varies with the type of cancer in question. METHODS: We report here a detailed study to evaluate the function of PKR in hepatitis C virus genotype 4 (HCV-4) infected patients. PKR gene was quantitated in HCV related malignant and non-malignant liver tissue by RT-PCR technique and the association of HCV core and PKR was assessed. RESULTS: If PKR functions as a tumour suppressor in this system, its expression would be higher in chronic hepatitis tissues. On the contrary our study demonstrated the specific association of HCV-4 with PKR expressed in hepatocellular carcinoma (HCC) tissues, leading to an increased gene expression of the kinase in comparison to chronic hepatitis tissues. This calls into question its role as a tumour suppressor and suggests a positive regulatory role of PKR in growth control of liver cancer cells. One limitation of most of other studies is that they measure the levels rather than the quantitation of PKR gene. CONCLUSION: The findings suggest that PKR exerts a positive role in cell growth control of HCV-4 related HCC, obtaining a cut-off value for PKR expression in liver tissue provides the first evidence for existence of a viral activator of PKR. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1267826959682402.

Immunohistochemical expression of mismatch repair genes (hMSH2 and hMLH1) in hepatocellular carcinoma in Egypt.

Egypt has the highest prevalence rate of hepatitis C virus (HCV) infection in the world. HCV contributes to the development of about 70% of hepatocellular carcinoma (HCC) cases. Understanding the molecular basis of hepatocarcinogenesis is important for planning the therapeutic regimen for HCC patients. To clarify the possible role of mismatch repair (MMR) genes in HCV-related HCC, we studied 50 HCV-related HCC specimens (28 of which were with adjacent non-cancerous cirrhotic liver tissue, ANCLT) and 30 specimens of chronic liver disease (CLD) with no evidence of HCC. All cases were examined immunohistochemically to demonstrate the protein expression of hMSH2 and hMLH1. Thirty-two (64%) and 35 (70%) of the HCC cases revealed reduced expression of hMSH2 and hMLH1, respectively. Reduced expression of both the proteins was obtained in 26 (52%) of the HCC cases. The expression of hMSH2 and hMLH1 was reduced in 53.6% and 64.3% of ANCLT cases, respectively, with no significant difference between HCC and ANCLT. All 30 specimens of CLD had preserved expression of hMSH2 and hMLH1. Multivariate analysis showed that the reduced expression of hMSH2 or hMLH1 was significantly associated with higher grades of the tumor (p = 0.002 and 0.02, respectively).The relationships of these MMR genes with other clinicopathologic factors were not significant. Reduced expression of hMSH2 and hMLH1 in both HCC and ANCLT suggests that this event occurs at early stages of HCV-related hepatocarcinogenesis. Moreover, the significant association between reduced expression of both MMR genes and poor histologic grades of the tumor claims that these proteins are involved in the process of cancer progression.

Effect of propolis versus metronidazole and their combined use in treatment of acute experimental giardiasis.

Propolis, a honey bee product, gained popularity in alternative medicine. Its prophylactic and therapeutic effects were experimentally evaluated. One hundred and fifty immunocompetent mice were orally infected by 5 x 10(5) axenically cultivated Giardia lamblia trophozoites. The trophozoite count in intestine, interferon-gamma serum level, histopathological examination of duodenal and jejunal sections were assessed for evaluation of propolis and metronidazole (MTZ) effect after 6 & 12 days post infection (p.i). Also, T-lymphocyte profile in blood was investigated 12 days p.i using flow cytometry (FCM). Propolis as prophylaxis showed a significant decrease in intensity of infection, together with a significant increase in IF-gamma serum level and increase in CD4+: CD8+T-cell ratio. In treatment it gave a highly significant decrease in trophozoite count than that obtained by MTZ 6 days after infection but the efficacy was almost equal after 12 days. The mice treated with propolis alone showed a reversed CD4+: CD8+ T-lymphocyte ratio, such strong immune enhancing effect resulted in an undesirable increase in inflammatory response at intestinal level. The combined therapy showed a stronger efficacy in reducing the parasite count than that gained by each drug alone. Their combined use caused an immunological balance as shown by the T-lymphocyte profile that saved the intestinal homeostasis and histological architecture.