Pathology and Laboratory Medicine Institute

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Pathology and Laboratory Medicine Institute

and Laboratory, United States
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Szoko N.,Case Western Reserve University | Mcshane A.J.,Pathology and Laboratory Medicine Institute | Natowicz M.R.,Case Western Reserve University
Autism Research | Year: 2017

Proteomics, the large-scale study of protein expression in cells and tissues, is a powerful tool to study the biology of clinical conditions and has provided significant insights in many experimental systems. Herein, we review the basics of proteomic methodology and discuss challenges in using proteomic approaches to study autism. Unlike other experimental approaches, such as genomic approaches, there have been few large-scale studies of proteins in tissues from persons with autism. Most of the proteomic studies on autism used blood or other peripheral tissues; few studies used brain tissue. Some studies found dysregulation of aspects of the immune system or of aspects of lipid metabolism, but no consistent findings were noted. Based on the challenges in using proteomics to study autism, we discuss considerations for future studies. Apart from the complex technical considerations implicit in any proteomic analysis, key nontechnical matters include attention to subject and specimen inclusion/exclusion criteria, having adequate sample size to ensure appropriate powering of the study, attention to the state of specimens prior to proteomic analysis, and the use of a replicate set of specimens, when possible. We conclude by discussing some potentially productive uses of proteomics, potentially coupled with other approaches, for future autism research including: (1) proteomic analysis of banked human brain specimens; (2) proteomic analysis of tissues from animal models of autism; and (3) proteomic analysis of induced pluripotent stem cells that are differentiated into various types of brain cells and neural organoids. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

Samplaski M.K.,Glickman Urological and Kidney Institute | Zhou M.,Pathology and Laboratory Medicine Institute | Lane B.R.,Spectrum Health Hospital System | Herts B.,Cleveland Clinic | Campbell S.C.,Glickman Urological and Kidney Institute
International Journal of Urology | Year: 2011

Renal mass sampling (RMS) can be carried out by core biopsy or fine needle aspiration with each presenting potential advantages and limitations. The literature about RMS is confounded by a lack of standardized techniques, ambiguous terminology, imprecise definitions of accuracy, substantial rates of non-informative biopsies, and recurrent diagnostic challenges with respect to eosinophilic neoplasms. Despite these concerns, RMS has an expanding role in the evaluation and treatment of renal masses, in order to stratify biological aggressiveness and guide management that can range from surgery to active surveillance. Non-informative biopsies can be managed with surgical excision or repeat biopsy, with the latter showing encouraging results in recent studies. We propose a new classification in which all biopsies are categorized as non-informative versus informative, with the latter being subclassified as confirmed accurate, presumed accurate or confirmed inaccurate. This terminology will facilitate the comparison of results from various studies and stimulate progress. Incorporation of novel biomarkers and molecular fingerprinting into RMS protocols will likely allow for more rational management of patients with renal masses in the near future. © 2010 The Japanese Urological Association.

Kottke-Marchant K.,Pathology and Laboratory Medicine Institute | Kottke-Marchant K.,Cleveland Clinic | Davis B.H.,Trillium Diagnostics LLC
Laboratory Hematology Practice | Year: 2012

Expertly edited and endorsed by the International Society for Laboratory Hematology, this is the newest international textbook on all aspects of laboratory hematology. Covering both traditional and cutting-edge hematology laboratory technology this book emphasizes international recommendations for testing practices. Illustrative case studies on how technology can be used in patient diagnosis are included. Laboratory Hematology Practice is an invaluable resource for all those working in the field. © 2012 Blackwell Publishing Ltd.

Zein N.N.,Digestive Disease Institute | Hanouneh I.A.,Digestive Disease Institute | Bishop P.D.,Heart and Vascular Institute | Samaan M.,Digestive Disease Institute | And 5 more authors.
Liver Transplantation | Year: 2013

The growing demand for liver transplantation and the concomitant scarcity of cadaveric livers have increased the need for living donor liver transplantation (LDLT). Ensuring the safety of donors and recipients is critical. The preoperative identification of the vascular and biliary tract anatomy with 3-dimensional (3D) printing may allow better preoperative surgical planning, avert unnecessary surgery in patients with potentially unsuitable anatomy, and thereby decrease the complications of liver transplant surgery. We developed a protocol and successfully 3D-printed synthetic livers (along with their complex networks of vascular and biliary structures) replicating the native livers of 6 patients: 3 living donors and 3 respective recipients who underwent LDLT. To our knowledge, these are the first complete 3D-printed livers. Using standardized preoperative, intraoperative, and postoperative assessments, we demonstrated identical anatomical and geometrical landmarks in the 3D-printed models and native livers. © 2013 American Association for the Study of Liver Diseases.

Bonkhoff H.,Pathology Laboratory | Wheeler T.M.,Baylor College of Medicine | Magi-Galluzzi C.,Pathology and Laboratory Medicine Institute | Montironi R.,Marche Polytechnic University | And 2 more authors.
Prostate | Year: 2013

BACKGROUND Although the term "intraductal carcinoma of the prostate" (IDC-P) was introduced almost 40 years ago, there is still the lack of appreciation that this entity represents a clinically aggressive disease that continues to be misreported under the diagnostic category of high grade prostatic intraepithelial neoplasia (HGPIN). METHODS Recent data obtained from histological, molecular, and clinical studies were reviewed to demonstrate that IDC-P significantly differs from HGPIN, and has a major impact in terms of diagnosis, prognosis and therapy of prostate cancer (PCa). RESULTS HGPIN is the only accepted precursor of PCa. Its diagnosis in prostate biopsies has no prognostic implications, and does not dictate therapeutic decisions. By contrast, IDC-P correlates with a worse pathological and clinical outcome. IDC-P differs from HGPIN by distinct histological and molecular features. Recent clinical studies report that IDC-P is associated with neoadjuvant androgen deprivation therapy (ADT) and, chemotherapy (CT) failure as well as early disease recurrence after external beam radiation. Finally, IDC-P is associated with TMPRSS2-ERG gene fusion, which was reported to be regulated by estrogens and their receptors. CONCLUSIONS IDC-P is an aggressive phenotype of prostate cancer and predicts poor response to ADT, CT, and external beam radiation. IDC-P should be separated from HGPIN and should be reported in prostate biopsies and prostatectomy specimens. Prostate 73: 442-448, 2013. © 2012 Wiley Periodicals, Inc. Copyright © 2012 Wiley Periodicals, Inc.

Abd El-Latif A.,Glickman Urological and Kidney Institute | Watts K.E.,Pathology and Laboratory Medicine Institute | Elson P.,Taussig Cancer Institute | Fergany A.,Glickman Urological and Kidney Institute | Hansel D.E.,Cleveland Clinic
Journal of Urology | Year: 2013

Purpose: We determined the ability of bladder biopsy and transurethral resection of the bladder to accurately predict bladder cancer variants on radical cystectomy since certain variants may affect prognosis and treatment. Materials and Methods: We retrospectively evaluated the records of 302 patients who underwent biopsy and/or transurethral resection of the bladder followed by radical cystectomy from 2008 to 2010. The frequency of variant morphology and the sensitivity of the precystectomy material was determined using pathological findings at radical cystectomy as the final result. Results: Bladder cancer variants were identified in 159 patients (53%) on initial biopsy/transurethral resection and/or final pathological evaluation at radical cystectomy. The most common variant was urothelial carcinoma with squamous differentiation in 72 of 159 patients (45%), followed by micropapillary urothelial carcinoma in 41 (26%). In 9 patients (6%) variant morphology was identified only on biopsy/transurethral resection bladder and not on final radical cystectomy pathological assessment. The remaining 150 patients (94%) showed variant morphology on radical cystectomy with (79 or 53%) or without (71 or 47%) variant morphology on the preceding biopsy/transurethral resection. The sensitivity of variant detection showed a broad range by variant subtype. Overall, initial biopsy/transurethral resection sensitivity was 39% for predicting variant morphology on radical cystectomy. Conclusions: Overall sensitivity for predicting bladder cancer variants from biopsy/transurethral resection of the bladder sampling is relatively low. This is likely due to sampling and tumor heterogeneity rather than to an inaccurate pathological diagnosis. Additional predictive markers of variant morphology may be useful to determine which tumors contain aggressive variants that may alter outcomes or therapy. © 2013 American Urological Association Education and Research, Inc.

Zhang W.-M.,Pathology and Laboratory Medicine Institute | Natowicz M.R.,Pathology and Laboratory Medicine Institute | Natowicz M.R.,Cleveland Clinic | Natowicz M.R.,Genomic Medicine Institute | Natowicz M.R.,Pediatrics Institute
Clinical Biochemistry | Year: 2013

Objectives: Determinations of cerebrospinal fluid (CSF) lactate and pyruvate concentrations and CSF lactate:pyruvate (L/P) ratios are important in several clinical settings, yet published normative data have significant limitations. We sought to determine a large dataset of stringently-defined normative data for CSF lactate and pyruvate concentrations and CSF L/P ratios. Design and methods: We evaluated data from 627 patients who had determinations of CSF lactate and/or CSF pyruvate from 2001 to 2011 at the Cleveland Clinic. Inclusion in the normal reference population required normal CSF cell counts, glucose and protein and routine serum chemistries and absence of progressive brain disorder, epilepsy, or seizure within 24. h. Brain MRI, if done, showed no evidence of tumor, acute changes or basal ganglia abnormality. CSF cytology, CSF alanine and immunoglobulin levels, and oligoclonal band analysis were required to be normal, if done. Various inclusion/exclusion criteria were compared. Results: 92 patients fulfilled inclusion/exclusion criteria for a reference population. The 95% central intervals (2.5%-97.5%) for CSF lactate and pyruvate levels were 1.01-2.09. mM and 0.03-0.15. mM, respectively, and 9.05-26.37 for CSF L/P. There were no significant gender-related differences of CSF lactate or pyruvate concentrations or of CSF L/P. Weak positive correlations between the concentration of CSF lactate or pyruvate and age were noted. Conclusions: Using stringent inclusion/exclusion criteria, we determined normative data for CSF lactate and pyruvate concentrations and CSF L/P ratios in a large, well-characterized reference population. Normalcy of routine CSF and blood analytes are the most important parameters in determining reference intervals for CSF lactate and pyruvate. © 2012 The Canadian Society of Clinical Chemists.

Gruver A.M.,Pathology and Laboratory Medicine Institute | Peerwani Z.,Pathology and Laboratory Medicine Institute | Tubbs R.R.,Pathology and Laboratory Medicine Institute
Journal of Clinical Pathology | Year: 2010

Assessment of ERBB2 (HER2) status in breast carcinomas has become critical in determining response to the humanised monoclonal antibody trastuzumab. The current joint College of American Pathologists and the American Society of Clinical Oncology guidelines for the evaluation of HER2 status in breast carcinoma involve testing by immunohistochemistry and fluorescence in situ hybridisation (FISH). However, neither of these modalities is without limitations. Novel bright field in situ hybridisation techniques continue to provide viable alternatives to FISH testing. While these techniques are not limited to evaluation of the HER2 gene, the extensive number of studies comparing bright field in situ techniques with other methods of assessing HER2 status allow a robust evaluation of this approach. Analysis of the literature demonstrates that, when used to assess HER2 gene status, bright field in situ hybridisation demonstrates excellent concordance with FISH results. The average percentage agreement in an informal analysis of studies comparing HER2 amplification by chromogenic in situ hybridisation with FISH was 96% (SD 4%); κ coefficients ranged from 0.76 to 1.0. Although a much smaller number of studies are available for review, similar levels of concordance have been reported in studies comparing HER2 amplification by methods employing metallography (silver in situ hybridisation) with FISH. A summary of the advancements in bright field in situ hybridisation, with focus on those techniques with clinical applications of interest to the practicing pathologist, is presented.

Minca E.C.,Pathology and Laboratory Medicine Institute | Portier B.P.,Pathology and Laboratory Medicine Institute | Wang Z.,Pathology and Laboratory Medicine Institute | Lanigan C.,Pathology and Laboratory Medicine Institute | And 6 more authors.
Journal of Molecular Diagnostics | Year: 2013

ALK gene rearrangements in advanced non-small cell lung carcinomas (NSCLC) are an indication for targeted therapy with crizotinib. Fluorescence in situ hybridization (FISH) using a recently approved companion in vitro diagnostic class FISH system commonly assesses ALK status. More accessible IHC is challenged by low expression of ALK-fusion transcripts in NSCLC. We compared ultrasensitive automated IHC with FISH for detecting ALK status on 318 FFPE and 40 matched ThinPrep specimens from 296 patients with advanced NSCLC. IHC was concordant with FFPE-FISH on 229 of 231 dual-informative samples (31 positive and 198 negative) and with ThinPrep-FISH on 34 of 34 samples (5 positive and 29 negative). Two cases with negative IHC and borderline-positive FFPE-FISH (15% and 18%, respectively) were reclassified as concordant based on negative matched ThinPrep-FISH and clinical data consistent with ALK-negative status. Overall, after including ThinPrep-FISH and amending the false-positive FFPE-FISH results, IHC demonstrated 100% sensitivity and specificity (95% CI, 0.86 to 1.00 and 0.97 to 1.00, respectively) for ALK detection on 249 dual-informative NSCLC samples. IHC was informative on significantly more samples than FFPE-FISH, revealing additional ALK-positive cases. The high concordance with FISH warrants IHC's routine use as the initial component of an algorithmic approach to clinical ALK testing in NSCLC, followed by reflex FISH confirmation of IHC-positive cases. Copyright © 2013 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Gruver A.M.,Pathology and Laboratory Medicine Institute | Portier B.P.,Pathology and Laboratory Medicine Institute | Tubbs R.R.,Pathology and Laboratory Medicine Institute
Archives of Pathology and Laboratory Medicine | Year: 2011

Context.-Adenocarcinoma of the breast is the most frequent cancer affecting women in both developed and developing regions of the world. From the moment of clinical presentation until the time of pathologic diagnosis, patients affected by this disease will face daunting questions related to prognosis and treatment options. While improvements in targeted therapies have led to increased patient survival, these same advances have created the imperative to accurately stratify patients to achieve maximum therapeutic efficacy while minimizing side effects. In this evolving era of personalized medicine, there is an ever-increasing need to overcome the limitations of traditional diagnostic practice. Objective.-To summarize the molecular diagnostics traditionally used to guide prognostication and treatment of breast carcinomas, to highlight published data on the molecular classification of these tumors, and to showcase molecular assays that will supplement traditional methods of categorizing the disease. Dafa Sources. - A review of the literature covering the molecular diagnostics of breast carcinomas with a focus on the gene expression and array studies used to characterize the molecular signatures of the disease. Special emphasis is placed on summarizing evolving technologies useful in the diagnosis and characterization of breast carcinoma. Conclusions.-Available and emerging molecular resources will allow pathologists to provide superior diagnostic, prognostic, and predictive information about individual breast carcinomas. These advances should translate into earlier identification and tailored therapy and should ultimately improve outcome for patients affected bv this disease.

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