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Book Details
Abstract
Molecular pathology has significantly matured over the past decade to establish itself as a discipline in its own right. Patient diagnosis, prognosis, management and care have been influenced by molecular pathology testing algorithms on a global scale. Whether it pertains to carrier status of deleterious genes, diagnosis by molecular techniques, assessment of appropriate remission post treatment, parentage or forensics testing – molecular pathology continues to increase its presence and influence in the diagnostic laboratory armamentarium. Furthermore, intellectualization and proprietization of molecular pathology with respect to the discovery of new genes and or new techniques continues to pose new challenges of test ownership, legalities, liabilities, widespread acceptance and utility. This issue of Laboratory Clinics seeks to provide selective state of the art understanding of molecular pathology with respect to its relationship to key pathology disciplines as well as the current challenges and promise for the future.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front Cover | Cover | ||
| Molecular Pathology | i | ||
| Copyright\r | ii | ||
| Contributors | iii | ||
| Contents | v | ||
| Clinics In Laboratory Medicine\r | ix | ||
| Preface\r | xi | ||
| Introduction: The Impact of Molecular Pathology on the Practice of Pathology | 749 | ||
| Key points | 749 | ||
| References | 751 | ||
| Molecular Pathology Techniques | 753 | ||
| Key points | 753 | ||
| Polymerase chain reaction | 753 | ||
| Reverse transcription PCR | 754 | ||
| Real-time PCR | 754 | ||
| Multiplex PCR | 755 | ||
| xTAG technology | 755 | ||
| Strand displacement amplification | 755 | ||
| Transcription-mediated amplification | 756 | ||
| DNA sequencing | 757 | ||
| Pyrosequencing | 759 | ||
| Denaturing gradient gel electrophoresis | 762 | ||
| High-resolution melting analysis | 763 | ||
| Southern and northern hybridizations | 763 | ||
| Restriction fragment length polymorphism analysis | 764 | ||
| Reverse line-blot hybridization | 764 | ||
| Hybrid capture | 766 | ||
| Branched DNA assays | 767 | ||
| In situ hybridization | 770 | ||
| Other Technologies | 770 | ||
| References | 770 | ||
| Clinical Implication of MicroRNAs in Molecular Pathology | 773 | ||
| Key points | 773 | ||
| Introduction | 774 | ||
| Clinical perspective | 775 | ||
| Use of molecular pathology practice | 776 | ||
| Role of miRNAs in clinical specimens | 777 | ||
| Methodology and clinical implications | 778 | ||
| Purification of miRNA from Human Plasma | 778 | ||
| RT Reaction | 779 | ||
| Polymerase Chain Reaction | 779 | ||
| Methodology using the main resources of formalin-fixed tissues | 779 | ||
| FNA Tissue Collection | 780 | ||
| RNA Isolation | 781 | ||
| Real-Time RT-PCR | 781 | ||
| MiRNA Profiling | 781 | ||
| Advances made in characterizing miRNA profiling | 782 | ||
| Diagnostic and prognostic implications of miRNAs | 782 | ||
| Summary | 782 | ||
| References | 783 | ||
| Diagnostic Molecular Microbiology | 787 | ||
| Key points | 787 | ||
| Introduction | 787 | ||
| Probe techniques | 788 | ||
| Hybridization-Protection Assays | 788 | ||
| Hybrid Capture Technique | 789 | ||
| bDNA | 790 | ||
| Peptide Nucleic Acid Fluorescence In Situ Hybridization | 790 | ||
| Affirm VPIII Microbial Identification Test | 791 | ||
| Qualitative NAATs | 792 | ||
| Sexually Transmitted Disease Testing | 792 | ||
| Other Qualitative Assays | 794 | ||
| Quantitative techniques | 795 | ||
| Highly multiplexed PCR panels | 796 | ||
| Next-generation sequencing | 797 | ||
| Mass spectroscopy in microbiology | 798 | ||
| Late breaker techniques | 799 | ||
| References | 799 | ||
| Molecular Pathology in Transfusion Medicine | 805 | ||
| Key points | 805 | ||
| Overview | 805 | ||
| Advantages of molecular testing | 806 | ||
| Limitations of molecular testing | 807 | ||
| Molecular techniques used in transfusion medicine | 807 | ||
| Terminology and notation | 809 | ||
| Red cell antigen expression | 809 | ||
| Platelet antigen expression | 812 | ||
| Cell free nucleic acid testing | 814 | ||
| References | 814 | ||
| Molecular Diagnosis of Hematopoietic Neoplasms | 817 | ||
| Key points | 817 | ||
| Introduction | 817 | ||
| Molecular tests used to identify clonal T- and B-cell populations | 818 | ||
| Immunoglobulin Gene Rearrangement | 818 | ||
| T-Cell Gene Rearrangement | 818 | ||
| Southern Blot Analysis for Rearrangement of Immunoglobulin and TCR | 819 | ||
| PCR Assay for Rearrangement of Immunoglobulin and TCRs | 819 | ||
| Other molecular tests used in non-Hodgkin B- and T-cell lymphomas | 820 | ||
| BCL-2 Translocation Assay | 820 | ||
| Cyclin-D1 Translocation Assay | 821 | ||
| BCL-6 Translocation Assay | 821 | ||
| Cellular Myelocytomatosis Translocation Assay | 821 | ||
| Mucosal-associated Lymphoid Tissue Translocation Assay | 822 | ||
| Anaplastic Lymphoma Kinase Translocation Assay | 823 | ||
| Molecular tests used to identify defining cytogenetic abnormalities of the leukemias | 824 | ||
| Acute Myeloid Leukemia with t(15;17)(q22;q21)/PML-RARA | 824 | ||
| AML with t(8;21)(q22;q22)/RUNX1-RUNX1T1 | 824 | ||
| AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22)/CBFB-MYH11 | 825 | ||
| Acute Leukemia with 11q23/Mixed Lineage Leukemia Translocation | 825 | ||
| Acute leukemia with other translocations | 826 | ||
| AML with t(6;9)(p23;q34)/DEK-NUP214 | 826 | ||
| AML with inv(3)(q21q26.2) or t(3;3)(q21;q26.2)/RPN1-EVI1 | 826 | ||
| AML (Megakaryoblastic) with t(1;22)(p13;q13)/RBM15-MKL1 | 826 | ||
| Acute leukemia with gene mutations | 826 | ||
| NPM1 Mutated AML | 826 | ||
| CCAAT Enhancer Binding Protein Alpha Mutated AML | 827 | ||
| Fms-related Tyrosine Kinase 3 Gene Mutated AML | 827 | ||
| KIT Mutated Leukemia | 827 | ||
| Wilms’ Tumor Gene Mutated Leukemia | 827 | ||
| Leukemia Associated with Isocitrate Dehydrogenase 1 and 2 or “Brain And Acute Leukemia, Cytoplasmic” | 828 | ||
| ALL with t(9;22)(q34;q11)/BCR-ABL | 828 | ||
| ALL with t(12;21)(p13;q22)/TEL/RUNX1 | 828 | ||
| ALL with t(1;19)(q23;p13)/TCF3-PBX1 | 828 | ||
| ALL with t(4;11)(q11;q23)/AF4-MLL | 828 | ||
| CML with t(9;22)(q34;q11)/BCR-ABL1 | 829 | ||
| Mutations associated with MPN | 829 | ||
| Cytogenetic abnormalities associated with MDS | 830 | ||
| The importance of chromosomal aberrations in hematopoietic malignancies | 831 | ||
| Summary | 832 | ||
| References | 832 | ||
| Molecular Diagnostics in Colorectal Carcinoma | 835 | ||
| Key points | 835 | ||
| Introduction | 835 | ||
| Epidemiology | 836 | ||
| Clinical Features | 836 | ||
| Pathophysiology and molecular genetics | 836 | ||
| Traditional Vogelstein model and APC gene pathway | 837 | ||
| APC Gene | 837 | ||
| Hereditary nonpolyposis colon cancer | 839 | ||
| Limitations of molecular classification and correlates | 843 | ||
| Serrated Polyp Pathway | 845 | ||
| Sporadic MSI colorectal carcinoma | 846 | ||
| Pathologic features of MSI-H colorectal carcinoma | 846 | ||
| Shared by Both Inherited and Sporadic Tumors | 846 | ||
| MMR Testing | 847 | ||
| Scientific rationale | 847 | ||
| Clinical rationale | 848 | ||
| Best method | 848 | ||
| Quality assurance | 848 | ||
| Pitfalls | 848 | ||
| Recommendations | 849 | ||
| MMR IHC | 849 | ||
| MSI testing | 849 | ||
| BRAF Mutation Testing | 850 | ||
| CIMP Testing | 851 | ||
| KRAS mutation testing | 851 | ||
| Reporting guidelines (College of American Pathologists) | 851 | ||
| Germline testing | 852 | ||
| HNPCC | 852 | ||
| APC Gene | 852 | ||
| Algorithmic strategies for management of MMR colorectal carcinoma | 852 | ||
| Molecular investigation of lymph nodes in patients with colon cancer using one-step nucleic acid amplification | 854 | ||
| Molecular staging individualizing cancer management | 854 | ||
| Novel molecular screening approaches in CRC | 854 | ||
| Predictive and prognostic markers | 854 | ||
| Quantitative Multigene Reverse Transcriptase PCR Assay | 854 | ||
| KRAS Mutation | 855 | ||
| BRAF Mutation | 855 | ||
| Treatment of colorectal carcinoma | 855 | ||
| Future trends | 855 | ||
| Other Gene Mutations Associated with Resistance to Anti-EGFR Therapy33 | 855 | ||
| MicroRNAs | 855 | ||
| Upregulated microRNAs in colorectal carcinoma | 855 | ||
| Downregulated miRNAs: | 856 | ||
| Limitation | 856 | ||
| Epigenetic inactivation of endothelin 2 and endothelin 3 in colon cancer | 856 | ||
| Acknowledgments | 856 | ||
| References | 856 | ||
| Molecular Diagnostics in the Neoplasms of Small Intestine and Appendix | 861 | ||
| Key points | 861 | ||
| Introduction | 861 | ||
| Epidemiology | 862 | ||
| Small intestinal adenocarcinoma associated with celiac disease | 862 | ||
| Appendiceal adenocarcinoma | 862 | ||
| Ampullary adenocarcinoma | 862 | ||
| Mutations | 863 | ||
| Mutations in appendiceal carcinoma | 863 | ||
| Management Guidelines | 863 | ||
| Molecular testing | 863 | ||
| MSI | 863 | ||
| Screening patients with small intestine cancer | 864 | ||
| Follow-up germline testing for HNPCC | 864 | ||
| Pitfalls | 864 | ||
| KRAS | 864 | ||
| BRAF | 864 | ||
| Quality assurance (College of American Pathologists [CAP] guidelines) | 864 | ||
| References | 865 | ||
| Molecular Diagnostics in Esophageal and Gastric Neoplasms | 867 | ||
| Key points | 867 | ||
| Introduction | 867 | ||
| Epidemiology | 868 | ||
| Clinical features | 868 | ||
| Pathophysiology and molecular genetics | 868 | ||
| H pylori | 868 | ||
| Chromosomal Instability | 868 | ||
| Microsatellite Instability | 869 | ||
| Vascular Endothelial Growth Factor | 869 | ||
| HER-2 | 869 | ||
| HER-2 testing | 869 | ||
| Immunohistochemistry and fluorescence in situ hybridization | 869 | ||
| SISH | 869 | ||
| Other Abnormalities | 870 | ||
| Treatment | 870 | ||
| Morphology | 870 | ||
| References | 870 | ||
| Molecular Diagnostics in the Neoplasms of the Pancreas, Liver, Gall Bladder, and Extrahepatic Biliary Tract | 875 | ||
| Key points | 875 | ||
| Pancreatic Neoplasms | 875 | ||
| Epidemiology | 875 | ||
| Clinical Features | 876 | ||
| Pathophysiology and Molecular Genetics | 876 | ||
| Ductal adenocarcinoma | 876 | ||
| Other pancreatic neoplasms | 876 | ||
| Treatment | 876 | ||
| Liver neoplasms | 876 | ||
| Hepatic Adenoma | 876 | ||
| Epidemiology | 876 | ||
| Current Applications of Molecular Genetic Technologies to the Diagnosis and Treatment of Cutaneous Melanocytic Neoplasms | 881 | ||
| Key points | 881 | ||
| Introduction | 882 | ||
| The genetics of melanocytic lesions | 883 | ||
| The use of fluorescence in situ hybridization in the diagnosis of melanocytic neoplasms | 883 | ||
| The next round of molecular genetic technologies for the analysis of melanocytic neoplasms | 885 | ||
| Therapeutic approaches for metastatic melanoma in the molecular age | 886 | ||
| Ipilimumab (Anti-CTLA-4 Antibody) | 886 | ||
| BRAF Mutation and Anti-BRAF Agents | 886 | ||
| Zelboraf (vemurafenib) | 886 | ||
| Dabrafenib | 887 | ||
| KIT Inhibitors | 887 | ||
| Imatinib | 887 | ||
| References | 888 | ||
| Breast Carcinoma | 891 | ||
| Key points | 891 | ||
| Luminal A | 892 | ||
| Luminal B | 894 | ||
| ERBB2-enriched (Her-2/neu–positive) subtype | 894 | ||
| Basal-like subtype | 895 | ||
| Claudin Low Subtype | 895 | ||
| Molecular Apocrine Subtype | 896 | ||
| Interferon-Related Group | 896 | ||
| Molecular correlates of histologic subtypes | 896 | ||
| Invasive Lobular Carcinoma | 897 | ||
| Tubular Carcinoma/Cribriform Carcinoma | 898 | ||
| Mucinous and Neuroendocrine Carcinoma | 899 | ||
| Invasive Papillary Carcinoma | 899 | ||
| Invasive Micropapillary Carcinoma | 900 | ||
| Apocrine Carcinoma | 900 | ||
| Metaplastic Carcinoma | 901 | ||
| Medullary Carcinoma | 901 | ||
| Secretory Carcinoma | 902 | ||
| Adenoid Cystic Carcinoma | 902 | ||
| Ductal carcinoma in situ | 902 | ||
| In situ to invasive carcinoma: molecular pathways? | 903 | ||
| Summary | 904 | ||
| References | 904 | ||
| Gynecologic Cancers | 911 | ||
| Key points | 911 | ||
| Molecular pathogenesis of epithelial ovarian cancer | 911 | ||
| Type I Tumors | 912 | ||
| Low-grade serous carcinoma | 912 | ||
| Clear cell carcinoma | 912 | ||
| Low-grade endometrioid carcinoma | 913 | ||
| Mucinous carcinoma | 913 | ||
| Type II Carcinomas | 913 | ||
| Serous carcinoma | 913 | ||
| High-grade endometrioid carcinomas | 914 | ||
| Clinical Implications of the Dualistic Model of Ovarian Carcinogenesis | 914 | ||
| Uterine carcinomas: molecular features and pathogenesis | 915 | ||
| Type I Uterine Carcinoma | 915 | ||
| MSI | 916 | ||
| PTEN | 916 | ||
| The RAS-RAF-MEK-ERK signaling pathway | 917 | ||
| PIK3CA | 917 | ||
| β-Catenin gene (CTNNB1) | 917 | ||
| Treatment modalities | 918 | ||
| Type II Uterine Carcinoma | 918 | ||
| Uterine serous carcinoma | 919 | ||
| TP53 | 919 | ||
| Her-2/neu | 919 | ||
| EGFR | 920 | ||
| Clear cell carcinoma | 920 | ||
| Carcinosarcoma (malignant mixed müllerian tumor) | 920 | ||
| Summary | 921 | ||
| References | 921 | ||
| Index | 927 |