BackgroundPaxillin is a modular protein that localises to cell adhesion sites where it facilitates bidirectional communication between the intracellular actin cytoskeleton and the extracellular ...matrix. These complex and dynamic interactions are essential for cell adhesion, cell migration and cell survival. The authors have previously demonstrated that paxillin is overexpressed in lung cancer tissues and identified somatic paxillin mutations in 9% of lung cancers. A murine in vivo xenograft model of the most common paxillin mutation (A127T) showed increased cell proliferation and invasive tumour growth, establishing an important role for paxillin in the development of lung cancer.MethodsThe authors analysed 279 bronchoscopy-aided biopsy specimens from 92 high-risk patients. Adenocarcinoma with bronchioloalveolar features and pure bronchioloalveolar carcinoma (BAC) were analysed with fluorescence in situ hybridisation (FISH) and immunohistochemistry (IHC).ResultsPaxillin is overexpressed in premalignant areas of hyperplasia, squamous metaplasia and goblet cell metaplasia, as well as dysplastic lesions and carcinoma in high-risk patients. Concordance between increased paxillin gene copy number and paxillin overexpression was observed in cases of adenocarcinoma eusomic for chromosome 12.ConclusionsPaxillin overexpression occurs during the earliest stages of lung cancer development. FISH and IHC analysis of lung adenocarcinoma suggests that relatively small-scale genomic rearrangements of chromosome 12 are associated with paxillin overexpression in lung adenocarcinoma.
Abstract Objective: Toll-like receptor signaling activated by bacterial otitis media pathogens in the middle ear has been shown to play a key role in OM susceptibility, pathogenesis and recovery. ...Recent studies implicate microRNA 146 (miR-146) in regulation of inflammation via negative feedback of toll-like receptor signaling (TLR) in a wide variety of tissues, however its involvement in otitis media is unknown. Methods: Human middle ear epithelial cells were stimulated with proinflammatory cytokines, interluekin 1 beta or tumor necrosis factor alpha, for two to twenty-four hours. Middle ear biopsies were collected from children with otitis media with effusion (n=20), recurrent otitis media (n=9), and control subjects undergoing cochlear implantation (n=10). miR-146a, miR-146b expression was assayed by quantitative PCR (qPCR). Expression of miR-146 targets involved in TLR signaling, IRAK1 and TRAF6, was assayed by qPCR in middle ear biopsies. Middle ear biopsies were cryosectioned and epithelial thickness measured by a certified pathologist. Results:Proinflammatory cytokines induced expression of miR-146 in middle ear epithelial cells in vitro . Middle ear miR-146a and miR-146b expression was elevated in otitis media patients relative to control subjects and correlated with middle ear epithelial thickness. A trend towards inverse correlation was observed between miR-146 and TRAF6 expression in the clinical population. Conclusions:This report is the first to assess miRNA expression in a clinical population with OM. Findings herein suggest miR-146 may play a role in OM.
Abstract Chronic inflammation and infection are major risk factors for gastric carcinogenesis in adults. As chronic gastritis is common in Mexican children, diagnosis of Helicobacter pylori and other ...causes of gastritis are critical for the identification of children who would benefit from closer surveillance. Antral biopsies from 82 Mexican children (mean age, 8.3 ± 4.8 years) with chronic gastritis (36 H pylori +, 46 H pylori −) were examined for gastritis activity, atrophy, intestinal metaplasia (IM), and immunohistochemical expression of gastric carcinogenesis biomarkers caudal type homeobox 2 (CDX2), ephrin type-B receptor 4 (EphB4), matrix metalloproteinase 3 (MMP3), macrophage migration inhibitory factor (MIF), p53, β -catenin, and E-cadherin. Atrophy was diagnosed in 7 (9%) of 82, and IM, in 5 (6%) of 82 by routine histology, whereas 6 additional children (7%) (3 H pylori +) exhibited aberrant CDX2 expression without IM. Significant positive correlations were seen between EphB4, MMP3, and MIF ( P < .0001). Atrophy and follicular pathology were more frequent in H pylori + biopsies ( P < .0001), whereas IM and CDX2 expression showed no significant correlation with H pylori status. Antral biopsies demonstrating atrophy, IM, and/or aberrant CDX2 expression were seen in 21.95% (18/82) of the children, potentially identifying those who would benefit from closer surveillance and preventive dietary strategies. Biomarkers CDX2, EphB4, MMP3, and MIF may be useful in the workup of pediatric gastritis.
Thyroid nodules with longitudinal nuclear grooves have been widely regarded as synonymous with papillary thyroid carcinoma (PTC).
To study a series of cases of thyroid nodules that exhibited ...oncocytic (Hürthle cell) features and contained longitudinal nuclear grooves yet failed to display aggressive behavior or the full features of papillary thyroid carcinoma.
The clinicopathologic, immunohistochemical, and molecular genetic features of 15 patients with these features were studied. Next-generation sequencing was performed to examine 161 genes for oncogenic driver alterations associated with thyroid neoplasia.
The lesions occurred in 11 women and 4 men aged 27 to 80 years and measured 0.2 to 2.3 cm in diameter (mean, 1.1 cm). The tumors were well circumscribed and noninvasive and showed a proliferation of large cells with abundant granular cytoplasm and centrally placed nuclei displaying scattered longitudinal nuclear grooves. Immunohistochemical stains were negative for HBME-1, galectin-3, and CK19 in all cases. NRAS pQ61R was detected in 6 cases, KRAS p.Q61E in 1 case, and AKT2 p.E17K in 1 case. None of the genetic changes classically associated with conventional PTC or with high-grade thyroid malignant neoplasms were identified. Clinical follow-up in 9 patients showed no evidence of recurrence or metastases between 2 and 13 years (mean, 5.7 years).
Longitudinal nuclear grooves can be occasionally encountered in oncocytic (Hürthle cell) tumors and should not lead to a diagnosis of PTC in the absence of other features supporting that diagnosis.
The past 25 years have witnessed the field of molecular pathology evolving from an imprecisely defined discipline to a firmly established medical subspecialty that plays an essential role in patient ...care. During this time, the training, certification, and licensure requirements for directing and performing testing in a molecular pathology or molecular diagnostics laboratory have become better defined. The purpose of this document is to describe the various board certifications available to individuals seeking certification in molecular diagnostics at the level of laboratory director, supervisor, or technologist. Several national organizations offer certification in molecular pathology or molecular diagnostics for doctoral-level clinical scientists to function as the director of a molecular diagnostics laboratory. Furthermore, 12 states and Puerto Rico require licensing of medical technologists, including those working in molecular diagnostic laboratories. The information provided here updates a 2002 document by the Training and Education Committee of the Association for Molecular Pathology and has been expanded to include certification and licensing requirements for laboratory technologists.
Pediatric Neoplasia Jr, Alexander Craig Mackinnon
2012, 20120912, 2012-10-31
eBook
Pediatric Neoplasia: Advances in Molecular Pathology and Translational Medicine presents many of the major, relevant advances in molecular pathology that are occurring in the field of pediatric ...oncology and will serve as a useful overview for resident and attending physicians as well as scientists interested in understanding the molecular pathology of pediatric cancer in the context of clinical medicine. Chapters are based upon organ systems, and each is written by an expert or pair of experts in their field with subspecialty training and extensive clinical experience. Each chapter describes a variable number of tumors and includes an overview of the classification system and clinicopathological characteristics of each tumor. This is followed by a discussion of the molecular pathology relevant to a specific tumor, including specific molecular markers of the tumors, methods used for diagnosis or clinical management, clinical significance of the markers, and if appropriate, a description or discussion of current activities in translational research or issues that need to be addressed in the future. Pediatric Neoplasia: Advances in Molecular Pathology and Translational Medicine will be of great value to pathologists, oncologists, hematologists, internal medicine and pediatric specialists, as well as pharmaceutical professionals and translational and clinical researchers.
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