DOCSLIB.ORG

Non-Blood Sources of Cell-Free DNA for Cancer Molecular Profiling In

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

Critical Reviews in Oncology / Hematology 141 (2019) 36–42 Contents lists available at ScienceDirect Critical Reviews in Oncology / Hematology journal homepage: www.elsevier.com/locate/critrevonc Non-blood sources of cell-free DNA for cancer molecular profiling in clinical pathology and oncology T Giovanni Pontia, Marco Manfredinib, Aldo Tomasia a Department of Surgical, Medical, Dental & Morphological Sciences with Interest Transplant, Oncological & Regenerative Medicine, Division of Clinical Pathology, University of Modena & Reggio Emilia, Modena, Italy b Department of Surgical, Medical, Dental & Morphological Sciences with Interest Transplant, Oncological & Regenerative Medicine, Dermatology Unit, University of Modena & Reggio Emilia, Modena, Italy ARTICLE INFO ABSTRACT Keywords: Liquid biopsy can quantify and qualify cell-free (cfDNA) and tumour-derived (ctDNA) DNA fragments in the Cell-free DNA bloodstream. CfDNA quantification and mutation analysis can be applied to diagnosis, follow-up and therapeutic Non blood cfDNA management as novel oncologic biomarkers. However, some tumor-types release a low amount of DNA into the Liquid biopsy bloodstream, hampering diagnosis through standard liquid biopsy procedures. Several tumors, as such as brain, Biomarkers kidney, prostate, and thyroid cancer, are in direct contact with other body fluids and may be alternative sources Cancer diagnosis for cfDNA and ctDNA. Non-blood sources of cfDNA/ctDNA useful as novel oncologic biomarkers include cere- Cancer management brospinal fluids, urine, sputum, saliva, pleural effusion, stool and seminal fluid. Seminal plasma cfDNA, which can be analyzed with cost-effective procedures, may provide powerful information capable to revolutionize prostate cancer (PCa) patient diagnosis and management. In the near future, cfDNA analysis from non-blood biological liquids will become routine clinical practice for cancer patient diagnosis and management. 1. Introduction humoral balance for that individual. The most extensively studied body fluids are blood and urine, but many other liquids, such as cere- Over recent decades there has been a rapid expansion of knowledge brospinal fluid, saliva and seminal fluids have been analyzed in order to in the field of molecular biology and biochemistry, leading to the de- determine their diagnostic and prognostic potential. velopment of precision medicine and tailored therapies.(Lu and Liang, An example of a routinely applied liquid biopsy for patient man- 2016) The understanding of oncogenic pathways and neoplastic genetic agement is the dosage of prostate specific antigen (PSA) in the blood- signatures shed the conceptual basis for the development of liquid stream. However, the PSA protein is present both in healthy and in biopsy procedures and oncological-targeted therapies. Today, im- neoplastic prostate cells and therefore has a low sensitivity and speci- munohistochemical and biochemical tumor characterization are part of ficity for prostate cancer (PCa) diagnosis. In contrast, tumor-derived the routine process to define patient diagnosis and prognosis.(Ponti cell-free DNA (ctDNA) based techniques are more specific and can be et al., 2016; Hofman et al., 2018; Ponti et al., 2018d) applied to many body fluids in order to identify novel oncologic bio- The identification of new diagnostic and prognostic markers from markers for diagnosis, prognosis and monitoring of tumor therapeutic non-tumoral biological samples is an interesting field in continuous response. evolution. Liquid biopsy procedures have been developed to identify The presence of DNA within the non-cellular fraction of peripheral oncologic biomarkers in several body fluids such as blood, plasma, blood, termed cell-free DNA (cfDNA), was initially identified more than cerebrospinal liquid, seminal fluid, saliva and urine.(Ulrich and 50 years ago.(Ulrich and Paweletz, 2018; Stewart et al., 2018; Burgener Paweletz, 2018; Stewart et al., 2018; Burgener et al., 2017) The concept et al., 2017) Decades passed before cfDNA levels were found to be that body fluids may reveal the presence of several systemic diseases elevated within the serum of cancer patients, with at least a portion of dates back to ancient Greek and Indian history. The development of the cfDNA being tumor-derived (ctDNA). The advantage of ctDNA humoral theory was attributed to Hippocrates (ca. 460–370 BCE), and analysis from liquids other than blood is the collection of targeted in- its concepts were the base of Western medicine from antiquity through formation from a body fluid directly in contact with the tumor source to the 19th century. “Humoral” derives from the word “humor,” which (eg. cerebrospinal fluid for central nervous system neoplasm). Fur- in ancient greek means “fluid”, and health was defined as the proper thermore, contrary to what occurs with ctDNA in the bloodstream, E-mail address: [email protected] (G. Ponti). https://doi.org/10.1016/j.critrevonc.2019.06.005 Received 24 July 2018; Received in revised form 19 September 2018; Accepted 4 June 2019 1040-8428/ © 2019 Elsevier B.V. All rights reserved. G. Ponti, et al. Critical Reviews in Oncology / Hematology 141 (2019) 36–42 ctDNA in other bodily fluids are not diluted and higher concentrations complexes. of ctDNA are derived from active secretion and/or necrotic phenomena. In cancer, a portion of cfDNA originates from tumor cells, referred ctDNA harbors cancer-specific genetic and epigenetic alterations to as circulating-tumor DNA (ctDNA), and can harbor specific muta- that allow its detection and quantification using a variety of emerging tions corresponding to the patient's tumor. ctDNA profiling has recently techniques. The promise of convenient non-invasive access to the become an area of increasing clinical relevance in oncology, in parti- complex and dynamic molecular features of cancer through peripheral cular due to advances in the sensitivity of sequencing technologies, blood has galvanized translational researchers around this topic with allowing a reliable identification of cancer mutations. Several studies compelling routes to clinical implementation, particularly in the post showed high concordance between individual mutations found in -treatment surveillance setting. (Ulrich and Paweletz, 2018; Stewart ctDNA samples and tumor tissue.(Bettegowda et al., 2014) Cancer pa- et al., 2018; Burgener et al., 2017) Although analysis methods must tients have much higher cfDNA concentrations (0 to > 1000 mg/mL) contend with small quantities of ctDNA present in most patients and the than healthy individuals (0–100 ng/mL) and the total amount varies relative over-abundance of background cfDNA derived from normal among patients with comparable cancer type and stage.(Bettegowda tissues, recent technical innovations have led to dramatic improve- et al., 2014) Direct correlations between ctDNA level and tumor ments in the sensitivity of ctDNA detection. The collection of biologic burden, stage, vascularity and therapy response have been described for samples to isolate cfDNA is often repeatable, allowing for real-time and several cancers. dynamic monitoring of molecular changes.(Zeng et al., 2018) As a re- cfDNA can be found in plasma as well as other body fluids such as sult, ever more studies are investigating the clinical utility of ctDNA for urine, cerebral spinal fluid (CSF), pleural fluid, and saliva, among applications in treatment response assessment,(Dawson et al., 2013) others.(Stewart and Tsui, 2018) Depending on tumor type, different identification of emerging resistance mechanisms,(Mok et al., 2015; rates of cfDNA/ctDNA have been reported in blood samples. CtDNA was Tabernero et al., 2015) and minimal residual disease detection.(Guo detected in over 75% of patients with advanced pancreatic, ovarian, et al., 2016) In addition, ctDNA is released from multiple tumor regions, colorectal, bladder, gastroesophageal, breast, melanoma, hepatocel- and may thereby represent the whole molecular picture of a patient's lular, and head and neck cancers. However, levels below 50% were malignancy, potentially solving the problem of intra-tumor hetero- found in primary brain tumors, in kidney, prostate, and thyroid cancers, geneity,(L De Mattos-Arruda et al., 2014; Leticia De Mattos-Arruda (Bettegowda et al., 2014) and may be due to the influence other factors, et al., 2015; Jamal-Hanjani et al., 2016) which may lead to false-ne- such as blood-brain barrier restriction mechanisms, inflammatory or gative results and suboptimal therapy selection, and characterization of autoimmune processes that increase non-tumor cfDNA fraction, effec- clonal heterogeneity and selection. (Ulrich and Paweletz, 2018; Stewart tively diluting the ctDNA amount. The identification of ctDNA from et al., 2018; Burgener et al., 2017). biologic fluids other than blood, enables prompt diagnosis and a reli- In this review we explore the application of non-blood derived able genetic identification of cancer types, characterized by shedding ctDNA and cfDNA in the discovery of novel oncological biomarkers, low concentrations of ctDNA into the blood stream. These tumors are describing the existing evidence and focusing on the recent develop- often in direct contact with other body fluids, such as urine, saliva, ment of seminal plasma analysis. cerebrospinal fluid, pleural effusion or seminal liquid, releasing a considerable amount of ctDNA and creating a privileged source for non- 2. Biology of cell free DNA and cell tumoral DNA invasive ctDNA quantification and characterization. Cell-free DNA
Recommended publications
  • Lung, Epithelium, Alveolus – Hyperplasia

    Lung, Epithelium, Alveolus – Hyperplasia

    Lung, Epithelium, Alveolus – Hyperplasia 1 Lung, Epithelium, Alveolus – Hyperplasia Figure Legend: Figure 1 Lung, Epithelium, Alveolus - Hyperplasia in a male B6C3F1/N mouse from a chronic study. There is a small proliferation of alveolar epithelial cells with no inflammation. Figure 2 Lung, Epithelium, Alveolus - Hyperplasia in a male F344/N rat from a chronic study. There is no change in the normal alveolar architecture in this focus of alveolar epithelial hyperplasia. Figure 3 Lung, Epithelium, Alveolus - Hyperplasia in a male F344/N rat from a chronic study (higher magnification of Figure 2). The hyperplastic epithelial cells are cuboidal. Figure 4 Lung, Epithelium, Alveolus - Hyperplasia in a male B6C3F1/N mouse from a chronic study. The hyperplastic epithelial cells line slightly thickened alveolar septa. Figure 5 Lung, Epithelium, Alveolus - Hyperplasia in a male F344/N rat from a subchronic study. Alveolar epithelial hyperplasia secondary to inflammation is associated with numerous alveolar macrophages and minimal hemorrhage. Figure 6 Lung, Epithelium, Alveolus - Hyperplasia, Atypical from a male F344/N rat in a chronic study. Atypical cells (arrows) are enlarged with enlarged nuclei. Comment: Alveolar epithelial hyperplasia is a proliferation of type II pneumocytes and may be primary (Figure 1, Figure 2, Figure 3, and Figure 4) or secondary to type I pneumocyte injury or inflammation (Figure 5). Type II pneumocytes are thought to be the progenitors of type I cells. Type I pneumocytes are especially vulnerable to oxidant injury, and proliferation of type II pneumocytes is often seen following injury and loss of type I cells. When alveolar epithelial hyperplasia is secondary to type I pneumocyte damage, it is usually associated with inflammation, as opposed to primary alveolar epithelial hyperplasia, which is typically not associated with inflammation.
  • INTRINSIC FACTORS in the ETIOLOGY of NEOPLASMS' It Is

    INTRINSIC FACTORS in the ETIOLOGY of NEOPLASMS' It Is

    INTRINSIC FACTORS IN THE ETIOLOGY OF NEOPLASMS' CARL V. WELLER, MS., M.D. (From the Department of Pathology, University of Michigan) It is as true as it is trite that the cause of disease is never a single factor. Two elements always enter into etiology. One of these is inherent in the germ plasm of the individual; the other brought to bear upon the organism from beyond the confines of the germinal elements from which it has devel- oped. Better than internal and external, endogenous and exogenous, or con- stitutional and environmental, to designate these two groups of factors, are the terms intrinsic and extrinsic. Practical experience directs us to seek the relative importance of intrinsic and extrinsic factors whenever the causation of disease is studied, and we find that the two ingredients may be combined in every possible proportion. At one end of the series are diseases such as deaf mutism, transmitted as a simple recessive, in which the intrinsic element almost crowds out all other considerations. In the recessively sex-linked hemophilia, again the intrinsic element is so prominent that we see at once the mendelian significance of the process, although the bleeder may not be made known until the extrinsic factor, trauma, opens his blood vessels. The asthenic, dolichomorphic bodily configuration, which marks the phthisical habitus, is a familial character and therefore intrinsic, but it conditions infection by the tubercle bacillus in such a way as to give it serious or even lethal possibilities. When we consider syphilis, we find that the Treponema is no respecter of genetic constitution, yet sex and race may modify the character of the disease.
  • Absolute Measurement of the Tissue Origins of Cell-Free DNA in the Healthy State and Following Paracetamol Overdose Danny Laurent1, Fiona Semple1, Philip J

    Absolute Measurement of the Tissue Origins of Cell-Free DNA in the Healthy State and Following Paracetamol Overdose Danny Laurent1, Fiona Semple1, Philip J

    Laurent et al. BMC Medical Genomics (2020) 13:60 https://doi.org/10.1186/s12920-020-0705-2 RESEARCH ARTICLE Open Access Absolute measurement of the tissue origins of cell-free DNA in the healthy state and following paracetamol overdose Danny Laurent1, Fiona Semple1, Philip J. Starkey Lewis2, Elaine Rose1, Holly A. Black1, Jennifer Coe1, Stuart J. Forbes2, Mark J. Arends3, James W. Dear4 and Timothy J. Aitman1* Abstract Background: Despite the emergence of cell-free DNA (cfDNA) as a clinical biomarker in cancer, the tissue origins of cfDNA in healthy individuals have to date been inferred only by indirect and relative measurement methods, such as tissue-specific methylation and nucleosomal profiling. Methods: We performed the first direct, absolute measurement of the tissue origins of cfDNA, using tissue-specific knockout mouse strains, in both healthy mice and following paracetamol (APAP) overdose. We then investigated the utility of total cfDNA and the percentage of liver-specific cfDNA as clinical biomarkers in patients presenting with APAP overdose. Results: Analysis of cfDNA from healthy tissue-specific knockout mice showed that cfDNA originates predominantly from white and red blood cell lineages, with minor contribution from hepatocytes, and no detectable contribution from skeletal and cardiac muscle. Following APAP overdose in mice, total plasma cfDNA and the percentage fraction originating from hepatocytes increased by ~ 100 and ~ 19-fold respectively. Total cfDNA increased by an average of more than 236-fold in clinical samples from APAP overdose patients with biochemical evidence of liver injury, and 18-fold in patients without biochemically apparent liver injury. Measurement of liver-specific cfDNA, using droplet digital PCR and methylation analysis, revealed that the contribution of liver to cfDNA was increased by an average of 175-fold in APAP overdose patients with biochemically apparent liver injury compared to healthy subjects, but was not increased in overdose patients with normal liver function tests.
  • Villous Atrophy with Crypt Hyperplasia in Malignant Histiocytosis of the Nose

    Villous Atrophy with Crypt Hyperplasia in Malignant Histiocytosis of the Nose

    J Clin Pathol: first published as 10.1136/jcp.35.6.606 on 1 June 1982. Downloaded from J Cliii Pathol 1982;35:606-610 Villous atrophy with crypt hyperplasia in malignant histiocytosis of the nose K AOZASA Fronm Osaka University, Faculty oJ Medicine, Departmentt of Pathology, Osaka, Japanl SUMMARY Intestinal changes, mainly in the jejunum, were investigated in 13 cases of malignant histiocytosis at necropsy and who had presented as lethal midline granuloma.Villous atrophy with crypt hyperplasia was observed in all cases, and a proliferation of atypical histiocytes was observed in seven cases. In the remaining cases, histiocytes with normal morphology increased in number. These findings showed that a prolonged abnormal proliferation of histiocytes was present in the smnall intestine of these cases concurrently with the nasal lesions. The term malignant histiocytosis was introduced by from the jejunum were available in all cases. In one Rappaport, for "a systemic, progressive, and case, material from the jejunum was also obtained invasive proliferation of morphologically atypical at operation. Adequate clinical data were available histiocytes and their precursors".' Malignant histio- in II cases. cytosis of the intestine has been described in con- nection with malabsorption and ulcerative jejunitis.2 Results In these cases, peroral jejunal biopsy and surgical resection specimens showed villous atrophy with CLINICAL FINDtNGS crypt hyperplasia even in the jejunum remote from The 13 cases showed progressive and destructive areas of ulceration or frank lymphoma. Villous lesions in the nose and adjacent structures, which atrophy with crypt hyperplasia was suggested as a presented as clinical lethal midline granuloma. Nasal http://jcp.bmj.com/ prolonged cryptic phase of malignant histiocytosis.
  • Updates in Molecular Pathology of Central Nervous System Gliomas in Adults

    Updates in Molecular Pathology of Central Nervous System Gliomas in Adults

    UPDATES IN ONCOLOGY: PART 2 Updates in Molecular Pathology of Central Nervous System Gliomas in Adults MICHAEL PUNSONI, MD; JOHN E. DONAHUE, MD; HEINRICH D. ELINZANO, MD; TIMOTHY KINSELLA, MD 17 19 EN ABSTRACT Epidemiology Central nervous system (CNS) tumors are a heteroge- The incidence of CNS malignancies has been increasing. neous group of neoplasms divided into two broad cate- Most commonly, CNS tumors arise from glial cells, partic- gories, glial and non-glial. Non-glial tumors are derived ularly astrocytes and oligodendrocytes. Gliomas account from such diverse structures as the pineal gland, menin- for approximately 77% of primary malignant brain tumors ges, germ cells, and hematopoietic cells, as well as metas- (3). Most patients present between the fifth and seventh tases. Primary glial neoplasms, or those which originate decade of life. High-grade tumors are more common than from astrocytes, oligodendrocytes, or ependymal cells, low-grade and present a high risk of morbidity and mortal- include astrocytomas, oligodendrogliomas, ependymo- ity. The World Health Organization (WHO) in 2000 formu- mas, and mixed gliomas. Each entity has a unique mor- lated a classification system based on histologic findings phology and pattern of biologic behavior which portends that is used to stratify brain tumors into prognostic grades. a distinct prognosis and outcome. Individual outcomes High-grade gliomas (WHO grade III and IV) are most com- show some variability based on tumor location and age of monly seen in middle-aged to older adults, while grade II symptom onset; however, the underlying aggressiveness astrocytomas mainly affect younger adults. Management for of the tumor often dictates the time course of the disease.
  • 797 Circulating Tumor DNA and Circulating Tumor Cells for Cancer

    797 Circulating Tumor DNA and Circulating Tumor Cells for Cancer

    Medical Policy Circulating Tumor DNA and Circulating Tumor Cells for Cancer Management (Liquid Biopsy) Table of Contents • Policy: Commercial • Coding Information • Information Pertaining to All Policies • Policy: Medicare • Description • References • Authorization Information • Policy History • Endnotes Policy Number: 797 BCBSA Reference Number: 2.04.141 Related Policies Biomarkers for the Diagnosis and Cancer Risk Assessment of Prostate Cancer, #336 Policy1 Commercial Members: Managed Care (HMO and POS), PPO, and Indemnity Plasma-based comprehensive somatic genomic profiling testing (CGP) using Guardant360® for patients with Stage IIIB/IV non-small cell lung cancer (NSCLC) is considered MEDICALLY NECESSARY when the following criteria have been met: Diagnosis: • When tissue-based CGP is infeasible (i.e., quantity not sufficient for tissue-based CGP or invasive biopsy is medically contraindicated), AND • When prior results for ALL of the following tests are not available: o EGFR single nucleotide variants (SNVs) and insertions and deletions (indels) o ALK and ROS1 rearrangements o PDL1 expression. Progression: • Patients progressing on or after chemotherapy or immunotherapy who have never been tested for EGFR SNVs and indels, and ALK and ROS1 rearrangements, and for whom tissue-based CGP is infeasible (i.e., quantity not sufficient for tissue-based CGP), OR • For patients progressing on EGFR tyrosine kinase inhibitors (TKIs). If no genetic alteration is detected by Guardant360®, or if circulating tumor DNA (ctDNA) is insufficient/not detected, tissue-based genotyping should be considered. Other plasma-based CGP tests are considered INVESTIGATIONAL. CGP and the use of circulating tumor DNA is considered INVESTIGATIONAL for all other indications. 1 The use of circulating tumor cells is considered INVESTIGATIONAL for all indications.
  • Connections Between Warburg's and Szentgyorgyi's Approach About The

    Connections Between Warburg's and Szentgyorgyi's Approach About The

    Research iMedPub Journals Journal of Neoplasm 2017 http://www.imedpub.com/ ISSN 2576-3903 Vol.1 No.2:8 DOI: 10.217672576-3903.100008 Connections between Warburg’s and Szentgyorgyi’s Approach about the Causes of Cancer Szigeti GP1, Szasz O2 and Hegyi G3 1Institute of Human Physiology and Clinical Experimental Research, Semmelweis University, Hungary 2Department of Biotechnics, St. Istvan University, Hungary 3Department of Complementary and Alternative Medicine, University of Pecs, Hungary Corresponding author: Gabriella Hegyi, Department of Complementary and Alternative Medicine, University of Pecs, Hungary, Tel: +36 30 922-5347; E-mail: [email protected] Rec date: November 30, 2016; Acc date: December 26, 2016; Pub date: December 30, 2016 Citation: Szigeti GP, Szasz O, Hegyi G. Connections Between Warburg’s and Szentgyorgyi’s Approach About Causes of Cancer. J Neoplasm. 2017, 1: 2. to the environmental, diet and habit origins of malignant Abstract diseases [21-23]. Most widely, cancer is believed to be an abnormal tissue Numerous theories and hypotheses are published about triggered by a gene mutation. However, the proto-oncogene the causes of cancer and its hallmarks. Two remarkable and the oncogene appear not only in cancerous cases [24], but principles were established and debated for a long time. with pregnancy [25], with embryogenesis [26,27], with the The first is the Warburg-effect, which based on healing of wounds [28] and with the synthesis of growth mitochondrial dysfunction, connected to the intensive factors [29]. Oncogenes show a great variety of anti-apoptotic metabolic activity of the malignancy. The other is the functions with the cells taking part in the wound-healing [30].
  • MLH1 Single-Nucleotide Variant in Circulating Tumor DNA

    MLH1 Single-Nucleotide Variant in Circulating Tumor DNA

    www.nature.com/scientificreports OPEN MLH1 single‑nucleotide variant in circulating tumor DNA predicts overall survival of patients with hepatocellular carcinoma Soon Sun Kim1,4, Jung Woo Eun1,4, Ji‑Hye Choi2, Hyun Goo Woo2, Hyo Jung Cho1, Hye Ri Ahn3, Chul Won Suh3, Geum Ok Baek1, Sung Won Cho1 & Jae Youn Cheong1* Liquid biopsy can provide a strong basis for precision medicine. We aimed to identify novel single‑ nucleotide variants (SNVs) in circulating tumor DNA (ctDNA) in patients with hepatocellular carcinoma (HCC). Deep sequencing of plasma‑derived ctDNA from 59 patients with HCC was performed using a panel of 2924 SNVs in 69 genes. In 55.9% of the patients, at least one somatic mutation was detected. Among 25 SNVs in 12 genes, four frequently observed SNVs, MLH1 (13%), STK11 (13%), PTEN (9%), and CTNNB1 (4%), were validated using droplet digital polymerase chain reaction with ctDNA from 62 patients with HCC. Three candidate SNVs were detected in 35.5% of the patients, with a frequency of 19% for MLH1 chr3:37025749T>A, 11% for STK11 chr19:1223126C>G, and 8% for PTEN chr10:87864461C>G. The MLH1 and STK11 SNVs were also confrmed in HCC tissues. The presence of the MLH1 SNV, in combination with an increased ctDNA level, predicted poor overall survival among 107 patients. MLH1 chr3:37025749T>A SNV detection in ctDNA is feasible, and thus, ctDNA can be used to detect somatic mutations in HCC. Furthermore, the presence or absence of the MLH1 SNV in ctDNA, combined with the ctDNA level, can predict the prognosis of patients with HCC.
  • Clinicopathological Characteristics and KRAS Mutation Status of Endometrial Mucinous Metaplasia and Carcinoma JI-YOUN SUNG 1, YOON YANG JUNG 2 and HYUN-SOO KIM 3

    Clinicopathological Characteristics and KRAS Mutation Status of Endometrial Mucinous Metaplasia and Carcinoma JI-YOUN SUNG 1, YOON YANG JUNG 2 and HYUN-SOO KIM 3

    ANTICANCER RESEARCH 38 : 2779-2786 (2018) doi:10.21873/anticanres.12521 Clinicopathological Characteristics and KRAS Mutation Status of Endometrial Mucinous Metaplasia and Carcinoma JI-YOUN SUNG 1, YOON YANG JUNG 2 and HYUN-SOO KIM 3 1Department of Pathology, Kyung Hee University School of Medicine, Seoul, Republic of Korea; 2Department of Pathology, Myongji Hospital, Goyang, Republic of Korea; 3Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea Abstract. Background/Aim: Mucinous metaplasia of the papillary mucinous metaplasia suggests that papillary endometrium occurs as a spectrum of epithelial alterations mucinous metaplasia may be a precancerous lesion of a ranging from the formation of simple, tubular glands to certain subset of mucinous carcinomas of the endometrium. architecturally complex glandular proliferation with intraglandular papillary projection and cellular tufts. Endometrial metaplasia is defined as epithelial differentiation Endometrial mucinous metaplasia often presents a diagnostic that differs from the conventional morphological appearance challenge in endometrial curettage. Materials and Methods: of the endometrial glandular epithelium (1). Endometrial We analyzed the clinicopathological characteristics and the mucinous metaplasia is particularly relevant as it is mutation status for V-Ki-ras2 Kirsten rat sarcoma viral frequently encountered in endometrial curettage specimens oncogene homolog (KRAS) of 11 cases of endometrial obtained from peri-menopausal or postmenopausal women mucinous metaplasia. Electronic medical record review and (2). Mucinous epithelial lesions of the endometrium present histopathological examination were performed. KRAS a frequent disparity between cytological atypia and mutation status was analyzed using a pyrosequencing architectural alteration, and often present significant technique. Results: Cases were classified histopathologically diagnostic challenges to pathologists.
  • Repair, Regeneration, and Fibrosis Gregory C

    Repair, Regeneration, and Fibrosis Gregory C

    91731_ch03 12/8/06 7:33 PM Page 71 3 Repair, Regeneration, and Fibrosis Gregory C. Sephel Stephen C. Woodward The Basic Processes of Healing Regeneration Migration of Cells Stem cells Extracellular Matrix Cell Proliferation Remodeling Conditions That Modify Repair Cell Proliferation Local Factors Repair Repair Patterns Repair and Regeneration Suboptimal Wound Repair Wound Healing bservations regarding the repair of wounds (i.e., wound architecture are unaltered. Thus, wounds that do not heal may re- healing) date to physicians in ancient Egypt and battle flect excess proteinase activity, decreased matrix accumulation, Osurgeons in classic Greece. The liver’s ability to regenerate or altered matrix assembly. Conversely, fibrosis and scarring forms the basis of the Greek myth involving Prometheus. The may result from reduced proteinase activity or increased matrix clotting of blood to prevent exsanguination was recognized as accumulation. Whereas the formation of new collagen during the first necessary event in wound healing. At the time of the repair is required for increased strength of the healing site, American Civil War, the development of “laudable pus” in chronic fibrosis is a major component of diseases that involve wounds was thought to be necessary, and its emergence was not chronic injury. appreciated as a symptom of infection but considered a positive sign in the healing process. Later studies of wound infection led The Basic Processes of Healing to the discovery that inflammatory cells are primary actors in the repair process. Although scurvy (see Chapter 8) was described in Many of the basic cellular and molecular mechanisms necessary the 16th century by the British navy, it was not until the 20th for wound healing are found in other processes involving dynamic century that vitamin C (ascorbic acid) was found to be necessary tissue changes, such as development and tumor growth.
  • Injury and Cancer

    Injury and Cancer

    Case Western Reserve Law Review Volume 5 Issue 2 Article 4 1954 Injury and Cancer Lester Adelson Follow this and additional works at: https://scholarlycommons.law.case.edu/caselrev Part of the Law Commons Recommended Citation Lester Adelson, Injury and Cancer, 5 W. Rsrv. L. Rev. 150 (1954) Available at: https://scholarlycommons.law.case.edu/caselrev/vol5/iss2/4 This Article is brought to you for free and open access by the Student Journals at Case Western Reserve University School of Law Scholarly Commons. It has been accepted for inclusion in Case Western Reserve Law Review by an authorized administrator of Case Western Reserve University School of Law Scholarly Commons. [Winter Injury and Cancer by Lester Adelson, M.D. WITH LEGAL ANNOTATIONS BY OLIVER SCHROEDER, JR.* INTRODUCTION THE WORD "cancer" is one which is charged with emotion and fear, carrying with it implications of prolonged disability and slow, certain and painful death.' In considering and discussing the subject of cancer, diffi- culties frequently arise, not because not enough is known, but because so much is known that-is incorrect and untrue. A vast fund of misinformation and false information mis- leads the unwary stranger THE AUTHOR (A.B., 1935, Harvard Univer- and the uncritical observer. sity; M.D., 1939, Tufts College Medical School) is Chief Deputy Coroner and Patholo- Cancer is the second gist at the Coroner's Office, Cuyahoga County, leading cause of death, and Ohio, and Assistant Professor of Legal Medi- problems which arise in cine at the School of Medicine of Western Reserve University. connection with it are seen frequently.
  • Hematopoietic and Lymphoid Neoplasm Coding Manual

    Hematopoietic and Lymphoid Neoplasm Coding Manual

    Hematopoietic and Lymphoid Neoplasm Coding Manual Effective with Cases Diagnosed 1/1/2010 and Forward Published August 2021 Editors: Jennifer Ruhl, MSHCA, RHIT, CCS, CTR, NCI SEER Margaret (Peggy) Adamo, BS, AAS, RHIT, CTR, NCI SEER Lois Dickie, CTR, NCI SEER Serban Negoita, MD, PhD, CTR, NCI SEER Suggested citation: Ruhl J, Adamo M, Dickie L., Negoita, S. (August 2021). Hematopoietic and Lymphoid Neoplasm Coding Manual. National Cancer Institute, Bethesda, MD, 2021. Hematopoietic and Lymphoid Neoplasm Coding Manual 1 In Appreciation NCI SEER gratefully acknowledges the dedicated work of Drs, Charles Platz and Graca Dores since the inception of the Hematopoietic project. They continue to provide support. We deeply appreciate their willingness to serve as advisors for the rules within this manual. The quality of this Hematopoietic project is directly related to their commitment. NCI SEER would also like to acknowledge the following individuals who provided input on the manual and/or the database. Their contributions are greatly appreciated. • Carolyn Callaghan, CTR (SEER Seattle Registry) • Tiffany Janes, CTR (SEER Seattle Registry) We would also like to give a special thanks to the following individuals at Information Management Services, Inc. (IMS) who provide us with document support and web development. • Suzanne Adams, BS, CTR • Ginger Carter, BA • Sean Brennan, BS • Paul Stephenson, BS • Jacob Tomlinson, BS Hematopoietic and Lymphoid Neoplasm Coding Manual 2 Dedication The Hematopoietic and Lymphoid Neoplasm Coding Manual (Heme manual) and the companion Hematopoietic and Lymphoid Neoplasm Database (Heme DB) are dedicated to the hard-working cancer registrars across the world who meticulously identify, abstract, and code cancer data.