Hepatocellular adenomas (HCA) with activated ␤-catenin present a high risk of malignant transformation. To permit robust routine diagnosis to allow for HCA subtype classification, we searched new useful markers. We analyzed the expression of candidate genes by quantitative reverse transcription polymerase chain reaction QRT-PCR followed by immunohistochemistry to validate their specificity and sensitivity according to hepatocyte nuclear factor 1 alpha (HNF1␣) and ␤-catenin mutations as well as inflammatory phenotype. Quantitative RT-PCR showed that FABP1 (liver fatty acid binding protein) and UGT2B7 were downregulated in HNF1␣-inactivated HCA (P < 0.0002); GLUL (glutamine synthetase) and GPR49 overexpression were associated with ␤-catenin-activating mutations (P < 0.0005), and SAA2 (serum amyloid A2) and CRP (C-reactive protein) were upregulated in inflammatory HCA (P ‫؍‬ 0.0001). Immunohistochemistry validation confirmed that the absence of liver-fatty acid binding protein (L-FABP) expression rightly indicated HNF1␣ mutation (100% sensitivity and specificity), the combination of glutamine synthetase overexpression and nuclear ␤-catenin staining were excellent predictors of ␤-catenin-activating mutation (85% sensitivity, 100% specificity), and SAA hepatocytic staining was ideal to classify inflammatory HCA (91% sensitivity and specificity). Finally, a series of 93 HCA was unambiguously classified using our 4 validated immunohistochemical markers. Importantly, new associations were revealed for inflammatory HCA defined by SAA staining with frequent hemorrhages (P ‫؍‬ 0.003), telangiectatic phenotype (P < 0.001), high body mass index, and alcohol intake (P < 0.04). Previously described associations were confirmed and in particular the significant association between ␤-catenin-activated HCA and hepatocellular carcinomas (HCC) at diagnosis or during follow-up (P < 10 -5 ). Conclusion: We refined HCA classification and its phenotypic correlations, providing a routine test to classify hepatocellular adenomas using simple and robust immunohistochemistry. (HEPATOLOGY 2007;46:740-748.) H epatocellular adenomas (HCA) are rare benign liver tumors, most frequently occurring in women who are using oral contraception. Although HCA are mostly found as a single nodule, the presence of more than 10 in the liver indicates a specific nosological entity termed liver adenomatosis. 1 Two genetic alterations, the biallelic inactivation of hepatocyte nuclear factor 1 alpha (HNF1␣) and the activating mutation of ␤-catenin, have been described in HCA. 2,3 Recently, a comprehensive analysis of genetic, pathological, and clinical features in a series of 96 HCA enabled the identification of 4 HCA subtypes. 4 Biallelic HNF1␣ mutations defined the first group of HCA, phenotypically characterized by marked steatosis, lack of cytological abnormalities, and inflammatory infiltrates. Presence of a ␤-catenin-activating mutation defined the second group of HCA representing 15% of the cases generally characterized by a higher risk of malignant tr...

Immunology researchers are beginning to explore the possibilities of reproducibility, reuse and secondary analyses of immunology data. Open-access datasets are being applied in the validation of the methods used in the original studies, leveraging studies for meta-analysis, or generating new hypotheses. To promote these goals, the ImmPort data repository was created for the broader research community to explore the wide spectrum of clinical and basic research data and associated findings. The ImmPort ecosystem consists of four components–Private Data, Shared Data, Data Analysis, and Resources—for data archiving, dissemination, analyses, and reuse. To date, more than 300 studies have been made freely available through the Shared Data portal (www.immport.org/immport-open), which allows research data to be repurposed to accelerate the translation of new insights into discoveries.

To reveal impacts of sexual mode on genome content, we compared chromosome-scale assemblies of the outcrossing nematode Caenorhabditis nigoni to its self-fertile sibling species, C. briggsae. C. nigoni’s genome resembles outcrossing relatives, but encodes 31% more protein-coding genes than C. briggsae. C. nigoni genes lacking C. briggsae orthologs were disproportionately small and male-biased in expression. These include the male secreted short (mss) gene family, which encodes sperm surface glycoproteins conserved only in outcrossing species. Sperm from mss-null males of outcrossing C. remanei failed to compete with wild-type sperm, despite normal fertility in non-competitive mating. Restoring mss to C. briggsae males was sufficient to enhance sperm competitiveness. Thus, sex has a pervasive influence on genome content that can be used to identify sperm competition factors.