The Role Of P501s And Psa In The Diagnosis Of Metastatic Adenocarcinoma Of The Prostate

[No abstract available]335723724Xu, J., Kalos, M., Stolk, J.A., Zasloff, E.J., Zhang, X., Houghton, R.I., Identification and characterization of prostein, a novel prostate-specific protein (2001) Cancer Res, 61, pp. 1563-1568Xu, J., Stolk, J.A., Zhang, X., Silva, S.J., Houghton, R.I., Matsumura, M., Identification of differentially expressed genes in human prostate cancer using subtraction and microarray (2000) Cancer Res, 60, pp. 1677-1682Zhou, M., Chinnaiyan, A.M., Kleer, C.G., Lucas, P.C., Rubin, M.A., Alpha-Methylacyl-CoA racemase: A novel tumor marker over-expressed in several human cancers and their precursor lesions (2002) Am J Surg Pathol, 26, pp. 926-93

Constrictive pleuropericarditis: a dominant clinical manifestation in Whipple’s disease

Background: Whipple’s disease is a rare, multisystemic, chronic infectious disease which classically presents as a wasting illness characterized by polyarthralgia, diarrhea, fever, and lymphadenopathy. Pleuropericardial involvement is a common pathologic finding in patients with Whipple’s disease, but rarely causes clinical symptoms. We report the first case of severe fibrosing pleuropericarditis necessitating pleural decortication in a patient with Whipple’s disease. Case presentation: Our patient, an elderly gentleman, had a chronic inflammatory illness dominated by constrictive pericarditis and later severe fibrosing pleuritis associated with a mildly elevated serum IgG4 level. A pericardial biopsy showed dense fibrosis without IgG4 plasmacytic infiltration. The patient received immunosuppressive therapy for possible IgG4-related disease. His poor response to this therapy prompted a re-examination of the diagnosis, including a request for the pericardial biopsy tissue to be stained for Tropheryma whipplei. Conclusions: Despite a high prevalence of pleuropericardial involvement in Whipple’s disease, constrictive pleuropericarditis is rare, particularly as the dominant disease manifestation. The diagnosis of Whipple’s disease is often delayed in such atypical presentations since the etiologic agent, Tropheryma whipplei, is not routinely sought in histopathology specimens of pleura or pericardium. A diagnosis of Whipple’s disease should be considered in middle-aged or elderly men with polyarthralgia and constrictive pericarditis, even in the absence of gastrointestinal symptoms. Although Tropheryma whipplei PCR has limited sensitivity and specificity, especially in the analysis of peripheral blood samples, it may have diagnostic value in inflammatory disorders of uncertain etiology, including cases of polyserositis. The optimal approach to managing constrictive pericarditis in patients with Whipple’s disease is uncertain, but limited clinical experience suggests that a combination of pericardiectomy and antibiotic therapy is of benefit

Molecular testing in stage I–III non-small cell lung cancer : approaches and challenges

Precision medicine in non-small cell lung cancer (NSCLC) is a rapidly evolving area, with the development of targeted therapies for advanced disease and concomitant molecular testing to inform clinical decision-making. In contrast, routine molecular testing in stage I–III disease has not been required, where standard of care comprises surgery with or without adjuvant or neoadjuvant chemotherapy, or concurrent chemoradiotherapy for unresectable stage III disease, without the integration of targeted therapy. However, the phase 3 ADAURA trial has recently shown that the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), osimertinib, reduces the risk of disease recurrence by 80% versus placebo in the adjuvant setting for patients with stage IB–IIIA EGFR mutation-positive NSCLC following complete tumor resection with or without adjuvant chemotherapy, according to physician and patient choice. Treatment with adjuvant osimertinib requires selection of patients based on the presence of an EGFR-TKI sensitizing mutation. Other targeted agents are currently being evaluated in the adjuvant and neoadjuvant settings. Approval of at least some of these other agents is highly likely in the coming years, bringing with it in parallel, a requirement for comprehensive molecular testing for stage I–III disease. In this review, we consider the implications of integrating molecular testing into practice when managing patients with stage I–III non-squamous NSCLC. We discuss best practices, approaches and challenges from pathology, surgical and oncology perspectives

Bronchus-associated lymphoid tissue in kabuki syndrome with associated hyper-IgM syndrome/common variable immunodeficiency

A 28-year-old woman with a medical history significant for Kabuki syndrome with associated hyper-IgM syndrome/common variable immunodeficiency presented with a 3-month history of dyspnea, pleuritic pain, and nonproductive cough. Imaging demonstrated nodular infiltrates increasing toward the lung bases (Figure 1A). Bronchoscopy with lavage and transbronchial biopsies was performed to evaluate for an infectious or inflammatory etiology; however, results were unrevealing, and no infectious etiology was identified. Therefore, she underwent a video-assisted thoracic surgery biopsy that demonstrated nodular lymphoid hyperplasia with follicles centered on small airways and areas of organizing pneumonia (Figure 1B). Immunostains demonstrated follicles composed of CD31 T cells and CD201 B cells (Figure 1B) and no morphologic evidence of lymphoma or plasma cell neoplasm. Results were consistent with bronchus-associated lymphoid tissue (BALT). High-dose steroids were administered without resolution of symptoms or radiographic findings. A report of effective responses with rituximab and azathioprine in patients with common variable immunodeficiency who had a similar inflammatory lung process containing tertiary lymphoid structures, granulomas, and organizing pneumonia has been published (1). After four doses of rituximab (weekly), together with the initiation of azathioprine, her symptoms and radiographic findings improved (Figure 1C)

Tyrosine 23 Phosphorylation-Dependent Cell-Surface Localization of Annexin A2 Is Required for Invasion and Metastases of Pancreatic Cancer

The aggressiveness of pancreatic ductal adenocarcinoma (PDA) is characterized by its high metastatic potential and lack of effective therapies, which is the result of a lack of understanding of the mechanisms involved in promoting PDA metastases. We identified Annexin A2 (ANXA2), a member of the Annexin family of calcium-dependent phospholipid binding proteins, as a new molecule that promotes PDA invasion and metastases. We found ANXA2 to be a PDA-associated antigen recognized by post-treatment sera of patients who demonstrated prolonged survival following treatment with a PDA-specific vaccine. Cell surface ANXA2 increases with PDA development and progression. Knockdown of ANXA2 expression by RNA interference or blocking with anti-ANXA2 antibodies inhibits in vitro invasion of PDA cells. In addition, post-vaccination patient sera inhibits in vitro invasion of PDA cells, suggesting that therapeutic anti-ANXA2 antibodies are induced by the vaccine. Furthermore, cell-surface localization of ANXA2 is tyrosine 23 phosphorylation-dependent; and tyrosine 23 phosphorylation is required for PDA invasion. We demonstrated that tyrosine 23 phosphorylation resulting in surface expression of ANXA2 is required for TGFβ-induced, Rho-mediated epithelial-mesenchymal transition (EMT), linking the cellular function of ANXA2 which was previously shown to be associated with small GTPase-regulated cytoskeletal rearrangements, to the EMT process in PDA. Finally, using mouse PDA models, we showed that shRNA knock-down of ANXA2, a mutation at tyrosine 23, or anti-ANXA2 antibodies, inhibit PDA metastases and prolong mouse survival. Thus, ANXA2 is part of a novel molecular pathway underlying PDA metastases and a new target for development of PDA therapeutics

The Majority of MicroRNAs Detectable in Serum and Saliva Is Concentrated in Exosomes

There is an increasing interest in using microRNAs (miRNA) as biomarkers in autoimmune diseases. They are easily accessible in many body fluids but it is controversial if they are circulating freely or are encapsulated in microvesicles, particularly exosomes. We investigated if the majority of miRNas in serum and saliva are free-circulating or concentrated in exosomes. Exosomes were isolated by ultracentrifugation from fresh and frozen human serum and saliva. The amount of selected miRNAs extracted from the exosomal pellet and the exosome-depleted serum and saliva was compared by quantitative RT-PCR. Some miRNAs tested are ubiquitously expressed, others were previously reported as biomarkers. We included miRNAs previously reported to be free circulating and some thought to be exosome specific. The purity of exosome fraction was confirmed by electronmicroscopy and western blot. The concentration of miRNAs was consistently higher in the exosome pellet compared to the exosome-depleted supernatant. We obtained the same results using an equal volume or equal amount of total RNA as input of the RT-qPCR. The concentration of miRNA in whole, unfractionated serum, was between the exosomal pellet and the exosome-depleted supernatant. Selected miRNAs, which were detectable in exosomes, were undetectable in whole serum and the exosome-depleted supernantant. Exosome isolation improves the sensitivity of miRNA amplification from human biologic fluids. Exosomal miRNA should be the starting point for early biomarker studies to reduce the probability of false negative results involving low abundance miRNAs that may be missed by using unfractionated serum or saliva