Medical Pathology Commons^™

Comparative Analysis Of Tumor Capsule Thickness And Other Histologic Features In Encapsulated Follicular Variant Of Papillary Thyroid Carcinoma (Efvptc) And Noninvasive Follicular Thyroid Neoplasm With Papillary-Like Nuclear Features (Niftp), Brenda French, Stacey K. Mardekian, Md

Department of Pathology Honors Program Student Research Symposium

Recent reclassification of a subset of non-invasive encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) tumors as non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) has led to important changes in the clinical management of patients with these indolent lesions. Although there are established diagnostic criteria to differentiate NIFTP from EFVPTC, our objective was to determine further differences in histological characteristics between NIFTP and noninvasive EFVPTC. Additionally, we sought to identify histological differences between non-invasive and invasive EFVPTC lesions beyond the key finding of invasion. 68 encapsulated follicular lesions with papillary-like nuclear features from patients treated at Thomas Jefferson …

Implications Of Hobnail Features In Anaplastic Thyroid Carcinoma And Precursor Lesions, Caroline Dunne, Ba, Stacey K. Mardekian, Md

Department of Pathology Honors Program Student Research Symposium

Anaplastic thyroid carcinoma (ATC) has the poorest prognosis of all thyroid cancers. Morphologically, it is characterized by pleomorphic undifferentiated cells. In some cases, a differentiated precursor lesion, either papillary thyroid carcinoma (PTC) or follicular thyroid carcinoma, can be identified adjacent to the anaplastic component. There are certain morphological variants of PTC that are known to be associated with more aggressive behavior, but a recently described, understudied variant is the hobnail variant. It is characterized histologically by micropapillary structures lined by cells with abundant eosinophilic cytoplasm and apically-placed bulging nuclei. The aim of this study was to evaluate the frequency of …

Atypical Presentation Of Upshaw Schulman Syndrome: A Case Report, Goutham Ravipati, Bs, David Strayer, Md, Phd, Douglas Drelich, Md

Department of Pathology Honors Program Student Research Symposium

Thrombotic thrombocytopenic purpura (TTP) is a rare coagulation disorder with a typical clinical presentation of low platelets and excessive clotting. Mortality for this disorder may be high if untreated and therefore necessitates a high clinical suspicion. Here we describe a 46-year-old African American woman with a past medical history of multiple cerebrovascular accidents presenting to hematology after a suspected diagnosis of TTP. Presumptive diagnosis of acquired TTP called for treatment with IVIg, but a diagnosis of congenital TTP (Upshaw Schulman syndrome) was made after testing showed a lack of ADAMTS13 antibodies. Treatment with fresh frozen plasma (FFP) showed increase in …

Determining The Role Of Point-Of-Care Hemoglobin Testing In The Resuscitation Of Acutely Hemorrhaging Patients, Eugene P. Warnick, Alexis R. Peedin, Md

Department of Pathology Honors Program Student Research Symposium

Point-of-care hemoglobin (Hb) testing has not been evaluated in the resuscitation of acutely hemorrhaging patients to guide transfusion therapy. This study assessed the correlation of Hb values determined by point-of-care (EPOC) and traditional laboratory (CBC) methods in patients undergoing massive transfusion. All patients transfused per the massive transfusion protocol (MTP) between February 2013 and October 2017 were identified. The EPOC result was most often within 1 g/dL of the CBC result when EPOC resulted in a Hb between 7-10 g/dL and when drawn within 15 minutes of the CBC specimen. In patients on MTP with an EPOC Hb between 7-10 …

Metastatic Lobular Breast Carcinoma In A Meningioma: A Case Study, Sara Chapin, Msii, Lawrence C. Kenyon, Md, Phd

Department of Pathology Honors Program Student Research Symposium

Hormonal relationships between breast carcinoma and meningioma have long been reported in the literature. This association may be related to the widespread expression of progesterone receptors in meningiomas. Indeed, meningiomas are more common in women and may demonstrate increased growth during pregnancy. Women have an increased risk of meningioma following breast carcinoma diagnosis and vice versa. However, much more uncommon is a tumor to tumor metastases of breast carcinoma into a meningioma. We report a case of a 56 year old female with a past medical history of breast cancer, found to have a right sphenoorbital meningioma with metastatic lobular …

Credibility, Replicability, And Reproducibility In Simulation For Biomedicine And Clinical Applications In Neuroscience., Lealem Mulugeta, Andrew Drach, Ahmet Erdemir, C A Hunt, Marc Horner, Joy P. Ku, Jerry G Myers, Rajanikanth Vadigepalli, William W. Lytton

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Modeling and simulation in computational neuroscience is currently a research enterprise to better understand neural systems. It is not yet directly applicable to the problems of patients with brain disease. To be used for clinical applications, there must not only be considerable progress in the field but also a concerted effort to use best practices in order to demonstrate model credibility to regulatory bodies, to clinics and hospitals, to doctors, and to patients. In doing this for neuroscience, we can learn lessons from long-standing practices in other areas of simulation (aircraft, computer chips), from software engineering, and from other biomedical …

Puma Amplifies Necroptosis Signaling By Activating Cytosolic Dna Sensors., Dongshi Chen, Jingshan Tong, Liheng Yang, Liang Wei, Donna B. Stolz, Jian Yu, Jianke Zhang, Lin Zhang

Department of Microbiology and Immunology Faculty Papers

Necroptosis, a form of regulated necrotic cell death, is governed by RIP1/RIP3-mediated activation of MLKL. However, the signaling process leading to necroptotic death remains to be elucidated. In this study, we found that PUMA, a proapoptotic BH3-only Bcl-2 family member, is transcriptionally activated in an RIP3/MLKL-dependent manner following induction of necroptosis. The induction of PUMA, which is mediated by autocrine TNF-α and enhanced NF-κB activity, contributes to necroptotic death in RIP3-expressing cells with caspases inhibited. On induction, PUMA promotes the cytosolic release of mitochondrial DNA and activation of the DNA sensors DAI/Zbp1 and STING, leading to enhanced RIP3 and MLKL …

Self-Directed Learning Modules Enhance Mastery Of Diagnostic Imaging In Dissection-Based Anatomy Course For Physician Assistant Students, Guiyan Zhang, Bruce Fenderson, Xuan Zuo

Department of Pathology, Anatomy, and Cell Biology Posters

Abstract

The virtues of using computer-based learning modules as an alternative to traditional didactic lectures were tested in a human anatomy course for Physician Assistant (PA) students. Self-directed learning modules on diagnostic imaging were created using ArticulateTM software and provided online as homework assignments for PA students taking a human anatomy lecture and dissection laboratory course. These interactive self-learning modules replaced the content of traditional didactic lectures on the same topics that had been given in previous years. For the PA class of 2016 (n=103), diagnostic imaging was taught via traditional lectures, whereas for the PA class of 2017 (n=100), …

Induction Of Immune Surveillance Of The Dysmorphogenic Lens., Caitlin M. Logan, Caitlin J. Bowen, A. Sue Menko

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The lens has been considered to be an immune privileged site not susceptible to the immune processes normally associated with tissue injury and wound repair. However, as greater insight into the immune surveillance process is gained, we have reevaluated the concept of immune privilege. Our studies using an N-cadherin lens-specific conditional knockout mouse, N-cadΔlens, show that loss of this cell-cell junctional protein leads to lens degeneration, necrosis and fibrotic change, postnatally. The degeneration of this tissue induces an immune response resulting in immune cells populating the lens that contribute to the development of fibrosis. Additionally, we demonstrate that the lens …

Ros Control Mitochondrial Motility Through P38 And The Motor Adaptor Miro/Trak., Valentina Debattisti, Akos A. Gerencser, Masao Saotome, Sudipto Das, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Mitochondrial distribution and motility are recognized as central to many cellular functions, but their regulation by signaling mechanisms remains to be elucidated. Here, we report that reactive oxygen species (ROS), either derived from an extracellular source or intracellularly generated, control mitochondrial distribution and function by dose-dependently, specifically, and reversibly decreasing mitochondrial motility in both rat hippocampal primary cultured neurons and cell lines. ROS decrease motility independently of cytoplasmic [Ca2+], mitochondrial membrane potential, or permeability transition pore opening, known effectors of oxidative stress. However, multiple lines of genetic and pharmacological evidence support that a ROS-activated mitogen-activated protein kinase (MAPK), p38α, is …

Integration Of Metabolomics, Transcriptomics, And Microrna Expression Profiling Reveals A Mir-143-Hk2-Glucose Network Underlying Zinc-Deficiency-Associated Esophageal Neoplasia, Louise Y. Fong, Ruiyan Jing, Karl Smalley, Cristian Taccioli, Johannes Fahrmann, Dinesh K. Barupal, Hansjuerg Alder, John L. Farber, Oliver Fiehn, Carlo M. Croce

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Esophageal squamous cell carcinoma (ESCC) in humans is a deadly disease associated with dietary zinc (Zn)-deficiency. In the rat esophagus, Zn-deficiency induces cell proliferation, alters mRNA and microRNA gene expression, and promotes ESCC. We investigated whether Zn-deficiency alters cell metabolism by evaluating metabolomic profiles of esophageal epithelia from Zn-deficient and replenished rats vs sufficient rats, using untargeted gas chromatography time-of-flight mass spectrometry (n = 8/group). The Zn-deficient proliferative esophagus exhibits a distinct metabolic profile with glucose down 153-fold and lactic acid up 1.7-fold (P < 0.0001), indicating aerobic glycolysis (the "Warburg effect"), a hallmark of cancer cells. Zn-replenishment rapidly increases glucose content, restores deregulated metabolites to control levels, and reverses the hyperplastic phenotype. Integration of metabolomics and our reported transcriptomic data for this tissue unveils a link between glucose down-regulation and overexpression of HK2, an enzyme that catalyzes the first step of glycolysis and is overexpressed in cancer cells. Searching our published microRNA profile, we find that the tumor-suppressor miR-143, a negative regulator of HK2, is down-regulated in Zn-deficient esophagus. Using in situ hybridization and immunohistochemical analysis, the inverse correlation between miR-143 down-regulation and HK2 overexpression is documented in hyperplastic Zndeficient esophagus, archived ESCC-bearing Zn-deficient esophagus, and human ESCC tissues. Thus, to sustain uncontrolled cell proliferation, Zn-deficiency reprograms glucose metabolism by modulating expression of miR-143 and its target HK2. Our work provides new insight into critical roles of Zn in ESCC development and prevention. © Fong et al.

A Comparative Analysis Of The Paris System And Institutional Reporting System For Urine Cytology In Upper Tract Urothelial Specimens, Kim Hookim, Md, James P. Casey, Md, Rossitza Draganova-Tacheva, Md, Marluce Bibbo, Md, Charalambos C. Solomides, Md

Department of Pathology, Anatomy, and Cell Biology Posters

The authors of this abstract have no conflicts of interest

Introduction

Cytology is integral in the assessment of urothelial cell carcinoma (UCC). However, upper urinary tract (UUT) specimens are cytologically challenging due to limited tissue and reactive atypia. At our institution UUT biopsies are processed as cell blocks (CB). We compared our institution’s reporting system (IRS) with the recently proposed Paris System for Reporting Urine Cytology (PRS) (Table 1) in UUT specimens and correlated the findings with CB and follow-up resections.

Increased Density Of Axonal Spheroids In The Nucleus Gracilis Of The Lower Brainstem In Diabetic Versus Non-Diabetic Patients, Tiffany Morrison, Msiv, Lawrence C. Kenyon, Md, Phd

Department of Pathology, Anatomy, and Cell Biology Posters

Abstract

The presence of axonal spheroids is unusual in the absence of a clinical history of CNS injury. Nevertheless, increased numbers of axonal spheroids in the lower brainstem have been consistently observed in autopsied diabetic patients. A prospective comprehensive investigation of the density, size, and distribution of axonal spheroids in the brainstem and spinal cord was undertaken in 22 patients and correlated with comorbidities, age, and gender. In most cases, an increased density of axonal spheroids was identified within the nucleus gracilis of the lower brainstem. Moreover, the highest densities (p = 0.013) and circumferences (p = 0.002) of axonal …

Bcl-W Has A Fundamental Role In B Cell Survival And Lymphomagenesis., Clare M. Adams, Annette S. Kim, Ramkrishna Mitra, John K Choi, Jerald Z. Gong, Christine M. Eischen

Department of Cancer Biology Faculty Papers

Compromised apoptotic signaling is a prerequisite for tumorigenesis. The design of effective therapies for cancer treatment depends on a comprehensive understanding of the mechanisms that govern cell survival. The antiapoptotic proteins of the BCL-2 family are key regulators of cell survival and are frequently overexpressed in malignancies, leading to increased cancer cell survival. Unlike BCL-2 and BCL-XL, the closest antiapoptotic relative BCL-W is required for spermatogenesis, but was considered dispensable for all other cell types. Here, however, we have exposed a critical role for BCL-W in B cell survival and lymphomagenesis. Loss of Bcl-w conferred sensitivity to growth factor deprivation-induced …

Calcium Uptake Hotspots In The Mitochondria Of Cardiac Muscle At The Interface With Dyadic Sr, Sergio De La Fuente, Celia Fernandez-Sanz, Caitlin Vail, Elorm J. Agra, Kira Holmstrom, Junhui Sun, Jyotsna Mishra, Toren Finkel, Elizabeth Murphy, Suresh K. Joseph, Shey-Shing Sheu, György Csordás

Department of Pathology, Anatomy, and Cell Biology Posters

Introduction

• Control of the mitochondrial ATP production by SR-derived Ca2+ signals includes local, nanodomain Ca2+ transfer from ryanodine receptors (RyR2) to the mitochondrial matrix (excitation-bioenergetics coupling).

• Ca2+ crosses the inner mitochondrial membrane (IMM) via the mtCU, a low-affinity Ca2+-activated Ca2+ channel complex.

• The surface area of cardiac IMM is extensively enhanced by cristae folding; however, mitoplast patch clamp studies showed mtCU current density the lowest amongst a range of tissues (Fieni 2012. Nat Commun).

Activated Clotting Time (Act): Comparison Of The Hemochron Signature Elite And The Abbott I-Stat, Lilah Evans, Susanne Gallo, Joseph J. Leo, Barbara Goldsmith, Phd, Facb

Department of Pathology, Anatomy, and Cell Biology Posters

BACKGROUND

ACT is commonly used for heparin anticoagulation monitoring during procedures including cardiopulmonary bypass surgery, coronary angioplasty, and interventional radiology. To prevent thrombosis, moderate to high levels of heparin anticoagulation are required. The Hemochron Signature Elite (HSE, Accriva Diagnostics, formerly ITC, San Diego, CA) was implemented at TJUH as a replacement for the older model Hemochron Response (Accriva/ITC Model HRS.110, San Diego, CA). Operating room (OR) perfusionists reported irreproducible high results using HSE that could not be explained clinically. In consideration of use of i-STAT analyzers (Abbott Point of Care, Princeton, NJ) as an alternative to HSE, we performed a …

Performance Of Creatinine And Chloride On The Epoc Analyzer, Lilah Evans, Susanne Gallo, Stacey K. Mardekian, Barbara Goldsmith, Phd, Facb

Department of Pathology, Anatomy, and Cell Biology Posters

BACKGROUND

The epoc Blood Analysis System (Alere, Orlando, FL) performs blood gases, electrolytes, and metabolites using a Blood Gas Electrolyte and Metabolite (BGEM) Test Card panel on 92 uL of whole blood. The BGEM test card uses potentiometric sensors to measure sodium, potassium, ionized calcium, pH, pCO2; amperometric sensors to measure pO2, glucose, and lactate; and a conductometric sensor to measure hematocrit. Results are available in 3-10 minutes, depending upon the time between calibration and patient testing. TJUH implemented the epoc in its ICUs in 2012 to provide Point of Care (POC) results. Alere recently added creatinine and chloride sensors …

Use Of Propensity Score Matching To Identify A Strong Association Between Strategic Concentration To Mitochondria-Sr Associations Of The Mitochondrial Ca2+ Uniporter: Ca2+ Uptake Hotspots In The Cardiac Mitochondria, Sergio De La Fuente, Caitlin Vail, Elorm J. Agra, Kira Holmstrom, Junhui Sun, Jyotsna Mishra, Toren Kinkel, Elizabeth Murphy, Suresh K. Joseph, Shey-Shing Shen, György Csordás

Department of Pathology, Anatomy, and Cell Biology Posters

Introduction:

• Control of the mitochondrial ATP production by SR-derived Ca²⁺ signals includes local, nanodomain Ca²⁺ transfer from ryanodine receptors (RyR2) to the mitochondrial matrix (excitation-bioenergetics coupling).
• Ca²⁺ crosses the inner mitochondrial membrane (IMM) via the mtCU, a low-affinity Ca²⁺-activated Ca²⁺ channel complex.
• The surface area of cardiac IMM is extensively enhanced by cristae folding; however, mitoplast patch clamp studies showed mtCU current density the lowest amongst a range of tissues (Fieni 2012. Nat Commun).

Gaining Competencies During Early Medical Training: Medical Students As Teaching Assistants In Dissection-Based Anatomy Course, Martin T. Brown, Bruce Fenderson, Guiyan Zhang

Department of Pathology, Anatomy, and Cell Biology Posters

Introduction and Objectives

• In 2002, ACGME identified six ACGME Core Competencies: patient care; medical knowledge; practice-based learning and improvement; interpersonal and communication skills; professionalism; and systems-based practice.
• AAMC recommended lists of similar competencies for the curricula of medical schools. Competency based curricula have been widely implemented in medical schools.
• Effective shifting in the graduate medical educational programs has been reported in various clinical specialties.
• There is a lack of reported efforts and development on competency training in early preclinical years of medical education.

Objectives:

• To explore methods for strengthening medical students’ competency training during preclinical undergraduate medical education.
• To measure …

Microcystic, Elongated, And Fragmented (Melf) Pattern Invasion In Ovarian Endometrioid Carcinoma: Immunohistochemical Profile And Prognostic Implications, Allison F. Goldberg, Md, Lauren Cooper, Md, D. De Cotiis, Norman G. Rosenblum, Md, Phd, Joanna Chan, Md

Department of Pathology, Anatomy, and Cell Biology Resident's Posters

BACKGROUND

•Microcystic, Elongated and Fragmented (MELF) is a well-recognized pattern of uterine endometrioid carcinoma (UEC) associated with lymphovascular space invasion and occult lymph node metastasis

•MELF in UEC may be seen with Lynch Syndrome

•MELF in UEC is hypothesized to be histologic evidence of an epithelial mesenchymal transition

•MELF pattern invasion in ovarian endometrioid carcinoma (OEC) was first described at USCAP 2015 •

Current study evaluates MELF in OEC for

•Prognostic implications

•Immunohistochemical (IHC) profile related to

•Lynch Syndrome

•Epithelial mesenchymal transition

DESIGN

•42 consecutive cases of OEC without concurrent UEC (1996-2014) evaluated by 2 pathologists

•MELF defined as at …

Two Separate Colorectal Granular Cell Tumors: A Case Report, Danica N. Giugliano, Md, Danielle Fortuna, Md, Scott D. Goldstein, Md, Benjamin Philllips, Md, Gerald A. Isenberg, Md

Department of Surgery Posters

Introduction, Case Report, Discussion, Conclusion and References.

Microrna Dysregulation And Esophageal Cancer Development Depend On The Extent Of Zinc Dietary Deficiency., Louise Fong, Cristian Taccioli, Ruiyan Jing, Karl Smalley, Hansjuerg Alder, Yubao Jiang, Paolo Fadda, John Farber, Carlo M Croce

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Zinc deficiency (ZD) increases the risk of esophageal squamous cell carcinoma (ESCC), and marginal ZD is prevalent in humans. In rats, marked-ZD (3 mg Zn/kg diet) induces a proliferative esophagus with a 5-microRNA signature (miR-31, -223, -21, -146b, -146a) and promotes ESCC. Here we report that moderate and mild-ZD (6 and 12 mg Zn/kg diet) also induced esophageal hyperplasia, albeit less pronounced than induced by marked-ZD, with a 2-microRNA signature (miR-31, -146a). On exposure to an environmental carcinogen, ~16% of moderate/mild-ZD rats developed ESCC, a cancer incidence significantly greater than for Zn-sufficient rats (0%) (P ≤ 0.05), but lower than …

In-Silico Identification Of Prognostically Inversely Correlated Mirnas And Mrnas (Pic’S) In Multiple Cancers, Chirayu Pankaj Goswami, Zi-Xuan Wang

Department of Pathology, Anatomy, and Cell Biology Posters

Despite numerous methods available to identify potential mRNA targets for miRNAs, prognostic relationship of these molecules in diseases like cancers where deregulation of gene expression is a major pathogenic factor, has not yet been emphasized. We performed in-silico identification of prognostically inversely correlated miRNA - mRNA pairs (PIC’s) in multiple cancers using expression data from The Cancer Genome Atlas. Partners in a PIC show inverse correlation of expression and opposite hazard implication. Using a three step approach, we identified a total of 1,253,443 PIC’s from 23 cancer types, several of which have previously been shown to have a predicted or …

Turn-Around-Time Improvements For Positive Blood Cultures From Incorporation Of Workflow Modifications, Brent Bobik, Allison F. Goldberg, Md, P. Prior, Amity L. Roberts, Phd, D(Abmm)

Department of Pathology, Anatomy, and Cell Biology Resident's Posters

Background:

Emergence of direct from positive blood culture bottle identification (ID) methods reveal opportunities for improving bacterial ID and select resistance marker detection turn-around-times. Each system has various advantages and disadvantages; each institution must select the method/s that best fit the laboratory and patient needs. Here we elucidate improvements in 24 hour workflow through incorporating multiple rapid technologies for positive blood culture ID into a 24 hour algorithm.

Methods:

MALDI-TOF (Bruker) analysis with sepsityper extraction (aerobic Gram-positive and anaerobic bacteria); MALDI-TOF analysis with serum separator tube concentration (Gram-negative bacteria); and a FilmArray Blood Culture Panel (Biofire) were utilized. MALDI was …

Gliopathy Of Demyelinating And Non-Demyelinating Strains Of Mouse Hepatitis Virus., Lawrence C. Kenyon, Kaushiki Biswas, Kenneth S Shindler, Manasi Nabar, Marjorie Stout, Susan T Hingley, Judith B Grinspan, Jayasri Das Sarma

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Demyelination in the central nervous system induced by neurovirulent strains of Mouse Hepatitis Virus (MHV) is mediated by the viral spike glycoprotein, but it is not clear whether the mechanism of this disease pathology involves direct viral infection of oligodendrocytes. Detailed studies of glial cell tropism of MHV are presented, demonstrating that direct MHV infection of oligodendrocytes differs between demyelinating (RSA59) and non-demyelinating (RSMHV2) viral strains both in vitro and in vivo. Our results indicate that direct injury of mature oligodendrocytes is an important mechanism of virus-induced demyelination. In vivo, RSA59 infection was identified in spinal cord gray and white …

Progtar: A Database Of Prognostically Inversely Correlated Mirnas And Genes (Pics) In Multiple Cancers, Chirayu Pankaj Goswami

Department of Pathology, Anatomy, and Cell Biology Posters

ABSTRACT

PROGTar is a database of Prognostically Inversely Correlated miRNA-mRNA pairs (PIC’s) in 23 cancer types. Partner miRNA and mRNA in a PIC show inverse correlation of expression and opposite hazards. We analyzed miRNA and mRNA expression data downloaded from The Cancer Genome Atlas (TCGA) in a 3 step approach to identify PICs in different cancer types. In first step we performed correlation analysis between miRNAs and mRNAs for each cancer type. This was followed by performing hazard analysis separately for miRNAs and mRNAs using expression data and survival related clinical variables. In the third step we merged the correlation …

Comprehensive Profiling Of Metaplastic Breast Carcinoma Reveals Frequent Over-Expression Of Pd-L1, Zoran Gatalica, Upasana Joneja, Md, Anatole Ghazalpour, Jeffrey Swensen, Rebecca Feldman, Fred Cai, Sting Chen, Nick Xiao, Sandeep Reddy, Semir Vranić

Department of Pathology, Anatomy, and Cell Biology Resident's Posters

Background:

Metaplastic breast carcinoma (MBC) is a rare subtype of breast carcinoma less responsive to conventional chemotherapy relative to usual breast carcinomas such as ductal and lobular subtype. In molecular terms, MBC usually clusters with triple negative breast cancers (TNBC), but MBCs portray a worse prognosis in comparison with TNBC. Published studies investigating MBCs for specific biomarkers of therapy response are rare and limited by the methodological approaches.

Methods:

297 samples [MBC (n=75), triple-negative breast cancer of no-special-type (TNBC-NOS, n=106), HER2-positive breast cancers (n=32) and luminal breast cancers (n=84)] were profiled using direct sequencing analysis [Illumina MiSeq Next Generation Sequencing …

T(3;8)(Q26;Q24) With Myc Rearrangement In Acute Myeloid Leukemia: A Case Report, Vandi Ly, Md, Renu Bajaj, Phd, Jerald Z. Gong, Md, Zi-Xuan Wang, Phd, Stephen C Peiper, Md, Guldeep Uppal, Md

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Rearrangements of 3q26 have been described in 5% of de novo or therapy related acute myeloid leukemia, myelodysplastic syndrome (MDS), and blast phase of chronic myeloid leukemia. The most common translocations involving 3q26 are t(3;12)(q26;p13), t(3;21)(q26;q22), t(3;3)(q21;q26), t(2;3)(p15∼23;q26∼27) and rarely t(3;7)(q26;q21). However, t(3;8)(q26;q24) with or without monosomy 7 is a rare phenomenon and has been reported in only 10 patients so far. Hereby, we describe a 58 year old patient who was diagnosed with refractory anemia with multilineage dysplasia. Cytogenetic studies revealed monosomy 7. He was then lost to follow-up. A year later he was found to have worsening cytopenias …

The Role Of Perlecan And Endorepellin In The Control Of Tumor Angiogenesis And Endothelial Cell Autophagy., Stephen Douglass, Atul Goyal, Renato V. Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

During tumor growth and angiogenesis there is a dynamic remodeling of tissue architecture often accompanied by the release of extracellular matrix constituents full of biological activity. One of the key constituents of the tumor microenvironment is the large heparan sulfate proteoglycan perlecan. This proteoglycan, strategically located at cell surfaces and within basement membranes, is a well-defined pro-angiogenic molecule when intact. However, when partially processed by proteases released during cancer remodeling and invasion, the C-terminal fragment of perlecan, known as endorepellin, has opposite effects than its parent molecule. Endorepellin is a potent inhibitor of angiogenesis by exerting a dual receptor antagonism …

Strategic Distribution Of The Mitochondrial Ca2+ Uniporter In Cardiac Mitochondria, Sergio De La Fuente, Caitlin Vail, Elorm J. Agra, Kira Holmstrom, Junhui Sun, Jyotsna Mishra, Toren Finkel, Elizabeth Murphy, Shey-Shing Sheu, György Csordás

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background:

1) Control of the mitochondrial ATP production by SR-derived Ca²⁺ signals includes local, nanodomain Ca²⁺ transfer from ryanodine receptors (RyR2) to the mitochondrial matrix (excitation-bioenergetics coupling).

2) Ca²⁺ crosses the inner mitochondrial membrane (IMM) via the mtCU, a low-affinity Ca²⁺-activated Ca²⁺ channel complex.

3) The surface area of cardiac IMM is extensively enhanced by cristae folding; however, mitoplast patch clamp studies showed mtCU current density the lowest amongst a range of tissues (Fieni 2012. Nat Commun).