Properties of STAT1 and IRF1 enhancers and the influence of SNPs.

BACKGROUND: STAT1 and IRF1 collaborate to induce interferon-γ (IFNγ) stimulated genes (ISGs), but the extent to which they act alone or together is unclear. The effect of single nucleotide polymorphisms (SNPs) on in vivo binding is also largely unknown. RESULTS: We show that IRF1 binds at proximal or distant ISG sites twice as often as STAT1, increasing to sixfold at the MHC class I locus. STAT1 almost always bound with IRF1, while most IRF1 binding events were isolated. Dual binding sites at remote or proximal enhancers distinguished ISGs that were responsive to IFNγ versus cell-specific resistant ISGs, which showed fewer and mainly single binding events. Surprisingly, inducibility in one cell type predicted ISG-responsiveness in other cells. Several dbSNPs overlapped with STAT1 and IRF1 binding motifs, and we developed methodology to rapidly assess their effects. We show that in silico prediction of SNP effects accurately reflects altered binding both in vitro and in vivo. CONCLUSIONS: These data reveal broad cooperation between STAT1 and IRF1, explain cell type specific differences in ISG-responsiveness, and identify genetic variants that may participate in the pathogenesis of immune disorders.

Solitary benign fibrous mesothelioma of the peritoneum: A rare entity in a 2-year-old child.

Solitary benign fibrous mesothelioma (BFM) is uncommon and is termed as solitary fibrous mesothelioma or localized fibrous mesothelioma. Although the most common site for its development is the pleural region (65%), it has also been reported in the peritoneum. They are mostly seen in adults (average age: 54 years). Herein, we present a case of BFM in a 2-year-old male child, who presented to our hospital with abdominal pain and a lump in the abdomen. Differential diagnosis included solitary fibrous tumor, gastrointestinal stromal tumor, and benign fibrous lesions of mesentery. Establishing a preoperative diagnosis is difficult on the basis of clinical parameters or imaging studies and final diagnosis can only be assessed based on the results of histopathological and immunohistochemical examination.

Role of morphometry and proliferative parameters in grading of urothelial neoplasms.

INTRODUCTION: Mean nuclear area of 10 nuclei (MNA-10), mitotic activity index (MAI) and Ki-67 are highly reproducible and can be routinely used as adjuncts to histopathological grading in classifying tumors. Assays of these biomarkers are non-invasive, rapid, easy to perform, more objective and accurate, with high sensitivity and specificity, and correlate well with tumor grade. MATERIAL AND METHODS: This study was conducted at the Department of Pathology PGIMS, Rohtak on 50 cases, of which 25 cases were high-grade, 15 low-grade, 6 Papillary Urothelial Neoplasm of Low Malignant Potentialand 4 reactive lesions as per the 2004 ISUP/WHO classification. MNA-10, MAI and Ki-67 immunoquantitation were performed on stained sections. RESULTS: The age of the patients varied from 35 to 87 years. Male: female ratio was 3.5:1. The mean MNA-10 (µm(2)) for High Grade Malignant Potential was 104.52 ±25.64 µm(2), which was significantly higher than in PUNLMP (47.64 ±10.23) and LMP (51.57 ±15.66). MAI (/10 HPF) showed an increasing trend from reactive lesions to HMP, with a mean of (3 ±1.16)/10 HPF to (21.36 ±5.31)/10 HPF respectively. Ki-67 labelling index, a proliferative marker, revealed increasing trend lowest with reactive lesions (10 ±2.83%) and highest in high grade tumors (65.96 ±14.44). Spearman's correlation showed maximum correlation between MAI and Ki-67 and the increasing grade of tumor. CONCLUSIONS: MNA-10 in combination with Ki-67 and MAI was found to be stronger than MNA-10 alone. MAI has high reproducibility in differentiating low and high grade, with simple assessment in paraffin embedded sections allowing adequate histopathological analysis and visualization of proliferating cells simultaneously. This multivariate grading model should be applied in routine grading to overcome interobserver variability and to increase reproducibility of grading.