Diagnostic utility of the combined use of HNF4A and GATA3 in distinction between primary and metastatic breast and gastric carcinomas.

Sometimes the distinction between gastric adenocarcinomas and breast carcinomas can be challenging. Hepatocyte nuclear factor 4-alpha (HNF4A) has been suggested as a potential marker in these cases. The aim of the present work was to evaluate the role of the combined use of HNF4A and GATA3 as immunohistochemical markers in distinction between primary and metastatic breast and gastric carcinomas. This retrospective study was conducted on (81) cases divided into four groups of cohorts: primary BC (cohort I, n = 25), primary GC (cohort II, n = 23), and metastases derived from both types of tumors designated as metastasis derived from BC (cohort III-A, n = 17) and metastasis derived from GC (cohort III-B, n = 16). We performed immunohistochemistry analysis of HNF4A and GATA3 in all (81) cases. HNF4A expression was seen in 22 of 23 primary gastric adenocarcinomas and was absent in all 25 primary breast carcinomas (sensitivity 95.7%, specificity 100%). HNF4A was seen in 15 of 16 metastatic gastric adenocarcinomas and was absent in all 17 metastatic breast carcinomas (sensitivity 93.8%, specificity 100%). GATA3 showed 92 and 88% sensitivity, and 95.7 and 100% specificity for primary breast carcinomas and metastatic breast carcinomas, respectively. Our data confirmed the potential utility of HNF4A as a diagnostic marker and can be used as an adjunct to GATA3 as an immunohistochemical panel to differentiate between breast and gastric carcinomas.

Differential Expression of Cytochrome C Oxidase Subunit I Along the Colorectal Adenoma: Carcinoma Progression.

Loss in apoptosis competence often results in augmented genomic instability contributing to carcinogenesis. Cytochrome c oxidase subunit I (CcOI) can help assess apoptosis resistance in paraffin-embedded biopsies. In total, 50 colorectal cases including 10 control cases of colectomy for non-neoplastic condition, 15 cases of adenomatous colorectal polyps, and 25 cases of colorectal carcinoma were investigated in this retrospective study for immunohistochemical expression of CcOI. The staining pattern of CcOI was assessed and indices of aberrant expression were calculated as crypt-restricted loss and overall decreased immunostaining (ODI). ODI calculated in the adenocarcinoma tumor tissue was designated as Tr ODI. The crypt-restricted loss and ODI indices of the aberrant CcOI expression are significantly higher in the adenomatous polyps group (2.5% and 47.54%) and in the non-neoplastic mucosa among adenocarcinoma group (2.78% and 49.1%) when they are compared with the control group (0.55% and 7.32%) (P<0.001). A highly significant correlation was noted between Tr ODI and the tumor grade, the nodal status, and the stage among adenocarcinomas. In conclusion, colonic tumors arise in a field of crypts with aberrations in CcOI expression. This aberration is linked to biologically aggressive tumors. CcOI immunostaining may be applied on mucosal samples from patients with colonic adenomatous polyps and patients with previous cancer colon resection to determine individuals who are in need for frequent colonoscopies and/or chemopreventive strategies. Future follow-up studies are warranted to determine the level of expression predictive of recurrence or progression.

The role of the tumor necrosis factor (TNF)--Fas L and HCV in the development of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a major public health problem in Egypt due to the high prevalence of hepatitis C viral (HCV) infection. The mechanism by which HCV exerts its carcinogenic effect on the liver is not yet understood. Previous research has suggested that perturbations of the Fas-Fas L tumor necrosis system could result in uncontrolled cancerous cell growth in the liver. This study aims to assess the relationship of Fas ligand (Fas L) to HCC. A total of 28 cases (HCC) and 56 controls (28 cirrhosis and 28 chronic hepatitis) were included in the study. Sera and tissue biopsies were tested for HCV antibody and HCV-RNA. Fas ligand expression in tissue was examined immunohistochemically using a rabbit purified polyclonal antibody. Levels of soluble Fas L were determined in serum by ELISA. The HCC cases were graded as: 17.9% Grade I, 32.1% Grade II, 35.7% Grade III and 14.3% were Grade IV. Among the cases, 81% had evidence of cirrhosis. All the cases and controls were positive for HCV-RNA. Tissue and serum PCR results were identical within the same subjects. Fas ligand cytoplasmic expression was more pronounced in HCC than in cirrhosis, and in cirrhosis more than in chronic hepatitis. This expression was higher with increasing grades of malignancy and in tissues adjacent to the tumor, than in those without nearby tumor. Soluble Fas L levels were higher in cases than in controls, with similar results as that of immunohistochemical expression. These results suggest that HCV and Fas ligand play a key role in hepatocarcinogenesis, consistent with the hypothesis that HCV induces overexpression of Fas ligand in the liver cells, resulting in escape from killing by the immune system cells, with subsequent uncontrolled growth of tissue and the development of malignancy.