Primary bladder adenocarcinoma versus metastatic colorectal adenocarcinoma: a persisting diagnostic challenge.

AIM: This study attempted to distinguish primary bladder adenocarcinoma (PBA) from metastatic colonic adenocarcinomas (MCA), which is a difficult diagnostic and clinical problem. METHODS: Twenty-four cases of bladder adenocarcinomas (12 primary & 12 metastatic colorectal) were included in the study with urothelial carcinoma (UC) and colonic adenocarcinoma (CA) as controls. A panel of immunohistochemical (IHC) stains along with fluorescence in-situ hybridization (FISH), using the UroVysion probe set, was performed. RESULTS: The majority of the PBAs presented with advanced disease. Enteric histologic subtype was the most common morphological variant. Strong nuclear with cytoplasmic-membranous staining of ß-catenin was seen in 75% of MCA and only 16.7% PBA (<10% staining cells). Although abnormal nuclear staining with E-cadherin was seen in both PBA and MCA, it was more frequent in former. CK-7, CK-20, villin and CDX-2 stains were not helpful in distinguishing the two entities. FISH did not reveal any unique differences in chromosomal abnormality between the two groups. CONCLUSION: Although there was a statistically significant difference in ß-catenin and E-cadherin staining between two groups, we did not find any IHC or FISH marker that was specific for PBA. Distinction between PBA and MCA remains a diagnostic problem and clinical correlation is vital before rendering a diagnosis. VIRTUAL SLIDES: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1393156268152357.

Renal oncocytoma: a comparative clinicopathologic study and fluorescent in-situ hybridization analysis of 73 cases with long-term follow-up.

Clinical studies have confirmed that renal oncocytoma (RO) is a benign neoplasm with excellent prognosis. In diagnostically challenging cases of renal oncocytic epithelial neoplasms, fluorescent in-situ hybridization (FISH) is increasingly being used and its ability to distinguish RO from chromophobe renal cell carcinoma (ChRCC) has been documented. In this study, we evaluated the differential diagnostic contribution of FISH in cases of RO.Clinicopathologic data and glass slides from 73 patients with RO were reviewed; 20 cases of ChRCC were included for comparison. FISH analysis of formalin-fixed, paraffin-embedded sections was performed using centromeric probes for chromosomes 1, 2, 7 and 17. FISH analysis revealed ROs had frequent loss of signal for chromosome 1 (56%) and 17 (44%). Tumors with more than one loss were common (41%) and 10% cases showed loss of all chromosomes examined. A total of 18% cases did not show any abnormality.Our study shows that chromosomal abnormalities in both ROs and ChRCCs are common with frequent loss of chromosomes 1 and 17. No association was found between overall patient survival and the extent of chromosomal abnormalities. FISH results, even those showing significant chromosomal abnormalities, should not alter the primarily morphology-based diagnosis of RO.

Immunodetection of DNA repair endonuclease ERCC1-XPF in human tissue.

The high incidence of resistance to DNA-damaging chemotherapeutic drugs and severe side effects of chemotherapy have led to a search for biomarkers able to predict which patients are most likely to respond to therapy. ERCC1-XPF nuclease is required for nucleotide excision repair of helix-distorting DNA damage and the repair of DNA interstrand crosslinks. Thus, it is essential for several pathways of repair of DNA damage by cisplatin and related drugs, which are widely used in the treatment of non-small cell lung carcinoma and other late-stage tumors. Consequently, there is tremendous interest in measuring ERCC1-XPF expression in tumor samples. Many immunohistochemistry studies have been done, but the antibodies for ERCC1-XPF were not rigorously tested for antigen specificity. Herein, we survey a battery of antibodies raised against human ERCC1 or XPF for their specificity using ERCC1-XPF-deficient cells as a negative control. Antibodies were tested for the following applications: immunoblotting, immunoprecipitation from cell extracts, immunofluorescence detection in fixed cells, colocalization of ERCC1-XPF with UV radiation-induced DNA damage in fixed cells, and immunohistochemistry in paraffin-embedded samples. Although several commercially available antibodies are suitable for immunodetection of ERCC1-XPF in some applications, only a select subset is appropriate for detection of this repair complex in fixed specimens. The most commonly used antibody, 8F1, is not suitable for immunodetection in tissue. The results with validated antibodies reveal marked differences in ERCC1-XPF protein levels between samples and cell types.