Search Results (3)

Background and Objectives: The assessment of HER2 status in invasive breast carcinomas (IBCs) is critical for determining treatment strategies. The aim of this study was to evaluate the FICTION technique as a potential method for assessing HER2 status and to compare it with the standard sequential immunohistochemistry (IHC)–in situ hybridization (ISH) assays. Materials and Methods: This study included 49 patients diagnosed with invasive breast carcinomas. HER2 status was assessed using both IHC+FISH and FICTION techniques, and the results were compared. Results: Comparative analysis demonstrated an 83.67% categorical agreement between IHC and IF using the ASCO/CAP system. The percentage of cells showing any degree of HER2 protein expression was higher with IF (73.77%) than with IHC (60.71%) (p = 0.00026). The in situ hybridization assays showed an excellent agreement, with a 90% or higher concordance. The concordance of the ASCO/CAP group classification of cases using both ISH assays (FICTION and standard FISH) was high (85, 7%). Agreement was 100% for the final classification of cases (Her2 positive/negative). Conclusions: We compared standard tests for Her2 protein expression and the gene copy number with a modified FICTION protocol. The study showed moderate agreement between IHC and IF for Her2 protein and excellent agreement between FISH and FICTION ISH for the gene copy number. Final Her2 status was unaffected by low IF IHC concordance. Optimizing the FICTION protocol could improve results. Combining protein and gene assays may enhance IBC patient stratification. Full article

We previously demonstrated that the Trp53-R270H mutation can drive prostate cancer (CaP) initiation using the FVB.129S4 (Trp53^tm3Tyj/wt); FVB.129S (Nkx3-1^{tm3(cre)Mmswt}) genetically engineered mouse model (GEM). We now validate this finding in a different model (B6.129S4-Trp53^tm3.1Tyj/J mice) and use RNA-sequencing (RNA-Seq) to identify genes which may contribute to Trp53 R270H-mediated prostate carcinogenesis. Wildtype (Trp53^WT/WT), heterozygous (Trp53^R270H/WT), and homozygous mice (Trp53^R270H/R270H) were exposed to 5 Gy irradiation to activate and stabilize p53, and thereby enhance our ability to identify differences in transcriptional activity between the three groups of mice. Mouse prostates were harvested 6 h post-irradiation and processed for histological/immunohistochemistry (IHC) analysis or were snap-frozen for RNA extraction and transcriptome profiling. IHC analyses determined that presence of the Trp53-R270H mutation impacts apoptosis (lower caspase 3 activity) but not cell proliferation (Ki67). RNA-Seq analysis identified 1378 differentially expressed genes, including wildtype p53 target genes (E.g., Cdkn1a, Bax, Bcl2, Kras, Mdm2), p53 gain-of-function (GOF)-related genes (Mgmt, Id4), and CaP-related genes (Cav-1, Raf1, Kras). Further understanding the mechanisms which contribute to prostate carcinogenesis could allow for the development of improved preventive methods, diagnostics, and treatments for CaP. Full article

Meningiomas represent the most common primary tumors of the central nervous system, but few microRNA (miRNA) profiling studies have been reported so far. Deep sequencing of small RNA libraries generated from two human meningioma biopsies WHO grades I (benign) and II (atypical) were compared to excess dura controls. Nineteen differentially expressed miRNAs were validated by RT-qPCR using tumor RNA from 15 patients and 5 meninges controls. Tumor suppressor miR-218 and miR-34a were upregulated relative to normal controls, however, miR-143, miR-193b, miR-451 and oncogenic miR-21 were all downregulated. From 10 selected putative mRNA targets tested by RT-qPCR only four were differentially expressed relative to normal controls. PTEN and E-cadherin (CDH1) were upregulated, but RUNX1T1 was downregulated. Proliferation biomarker p63 was upregulated with nuclear localization, but not detected in most normal arachnoid tissues. Immunoreactivity of E-cadherin was detected in the outermost layer of normal arachnoids, but was expressed throughout the tumors. Nuclear Cyclin D1 expression was positive in all studied meningiomas, while its expression in arachnoid was limited to a few trabecular cells. Meningiomas of grades I and II appear to share biomarkers with malignant tumors, but with some additional tumor suppressor biomarkers expression. Validation in more patients is of importance. Full article