Human pathology
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The progression of intestinal metaplasia to esophageal adenocarcinoma in patients with Barrett's esophagus is partly driven by chromosomal alterations that activate oncogenes and inactivate tumor suppressor genes. The goal of this study was to determine how alterations of 4 frequently affected genes correlate with the range of histopathologic lesions observed in resected esophagi of patients with Barrett's esophagus. Fluorescence in situ hybridization was used to assess 83 tissue sections from 10 Barrett's esophagus esophagogastrectomy specimens for chromosomal alterations of 8q24 (MYC), 9p21 (CDKN2A; alias P16), 17q12 (ERBB2), and 20q13.2 (ZNF217). ⋯ CDKN2A loss was the only abnormality detected in 20 (47%) of 43 areas of intestinal metaplasia. Polysomy, the most common abnormality in dysplastic epithelium and adenocarcinoma, was observed in 16 (57%) of 28 low-grade dysplasia, 22 (88%) of 25 high-grade dysplasia, and 16 (100%) of 16 adenocarcinoma. The findings of this study improve our understanding of the role that chromosomal instability and alterations of tumor suppressor genes such as CDKN2A and oncogenes such as ERBB2 play in the progression of intestinal metaplasia to adenocarcinoma in patients with Barrett's esophagus.
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Early detection and diagnosis of papillary thyroid carcinoma are important for successful management of patients. Liquid-based preparations (Thinprep) of fine needle aspirations from thyroid nodules are now widely used and are replacing conventional smears because residual samples can be used for ancillary tests. Detection of the BRAF(V600E) mutation in cytology specimens could aid in the diagnosis of papillary thyroid carcinoma. ⋯ The sensitivity of liquid-based preparation alone for diagnosis of papillary thyroid carcinoma was 71.4%. When BRAF(V600E) mutation analyses results were considered in conjunction with the cytologic diagnosis, the diagnostic sensitivity for detecting papillary thyroid carcinoma increased to 84.9% regardless of the method used to detect BRAF mutations. BRAF(V600E) mutation analysis using residual liquid-based preparation cytologic samples is, therefore, a powerful additional diagnostic tool for diagnosis of papillary thyroid carcinoma.
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Nitric oxide is believed to play a central role in nonspecific defense of upper airways. Patients with primary ciliary dyskinesia have very low concentration of nasal nitric oxide, which may contribute to the chronic upper airway diseases encountered by these patients. The mechanisms underlying this drop of nasal nitric oxide in primary ciliary dyskinesia are still unknown. ⋯ Nitric oxide synthase 3 staining was restricted to endothelial cells in both groups. In addition, reduced nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase activity was superimposable to nitric oxide synthases 2 and 3 immunostaining, suggesting a preserved NADPH-activity of nitric oxide synthase. We therefore conclude that the drop in nasal nitric oxide in patients with primary ciliary dyskinesia is not secondary to the loss of nitric oxide synthase expression.
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High-throughput gene expression profiling from formalin-fixed, paraffin-embedded tissues has become a reality, and several methods are now commercially available. The Illumina whole-genome complementary DNA-mediated annealing, selection, extension and ligation assay (Illumina, Inc) is a full-transcriptome version of the original 512-gene complementary DNA-mediated annealing, selection, extension and ligation assay, allowing high-throughput profiling of 24,526 annotated genes from degraded and formalin-fixed, paraffin-embedded RNA. This assay has the potential to allow identification of novel gene signatures associated with clinical outcome using banked archival pathology specimen resources. ⋯ We performed quantitative reverse transcriptase polymerase chain reaction validation of 4 genes using Taqman assays and in situ protein detection of 1 gene by immunohistochemistry. Functional cluster analysis of genes up-regulated in tumors with aggressive pattern of invasion suggests presence of genes involved in cellular cytoarchitecture, some of which already associated with tumor invasion. Identification of these genes provides biologic rationale for our histologic classification, with regard to tumor invasion, and demonstrates that the whole-genome complementary DNA-mediated annealing, selection, extension and ligation assay is a powerful assay for profiling degraded RNA from archived specimens when combined with quantitative reverse transcriptase polymerase chain reaction validation.
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Intraductal papillary mucinous neoplasm of the pancreas is attracting attention as a precursor lesion of the invasive ductal adenocarcinoma, whereas it has been reported that some intraductal papillary mucinous neoplasms do not display progression to malignancy and remain almost unchanged in size and morphology. Recent studies have reported that oncogene-induced senescence has been observed in neoplasms, especially in premalignant lesions, and that it can play an important role in preventing malignant progression. To clarify the presence of senescence in intraductal papillary mucinous neoplasms, we analyzed the expression of several markers of senescence. ⋯ For all 4 markers, the percentages of positive cases reached a peak in intraductal papillary mucinous neoplasm with low-grade dysplasia and showed significant decreasing trends in the transition from intraductal papillary mucinous neoplasm with low-grade dysplasia to intraductal papillary mucinous neoplasm with an associated invasive carcinoma. Our results indicate that senescence is induced in the early stage of intraductal papillary mucinous neoplasm and gradually attenuated according to the progression. It is suggested that senescence plays a role in preventing malignant progression of intraductal papillary mucinous neoplasm.