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Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology

Mohammed A Aleskandarany, Michel E Vandenberghe, Caterina Marchiò, Ian O Ellis, Anna Sapino, Emad A Rakha
Breast cancer (BC) displays striking clinical, morphological, and behavioural diversity within a single tumour and between tumours. Currently, mounting evidence indicates that the morphological heterogeneity of BC reflects an underlying spectrum of genetic and epigenetic portraits that control BC behaviour. Further understanding of BC heterogeneity will have an impact, not only on the routine diagnostic practices but also on patients' management decisions. Phenomena like diagnostic inconsistencies and therapeutic resistance, both primary and acquired, could be attributed, at least in part, to tumour heterogeneity within the same cancer and between the primary disease and subsequent recurrences...
February 10, 2018: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
Eleni Orphanidou-Vlachou, Sarah E Kohe, Marie-Anne Brundler, Lesley MacPherson, Yu Sun, Nigel Davies, Martin Wilson, Xiaoyan Pan, Theodoros N Arvanitis, Richard G Grundy, Andrew C Peet
AIMS: Metabolite levels can be measured non-invasively using in vivo 1H magnetic resonance spectroscopy (MRS). These tumour metabolite profiles are highly characteristic for tumour type in childhood brain tumours; however, the relationship between metabolite values and conventional histopathological characteristics has not yet been fully established. This study systematically tests the relationship between metabolite levels detected by MRS and specific histological features in a range of paediatric brain tumours...
February 10, 2018: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
Xavier Sagaert, Arno Vanstapel, Sanne Verbeek
Colorectal cancer is not one disease but rather a collection of neoplastic diseases. Due to heterogeneity in the disease biology, therapy response, and prognosis, extensive disease stratification is required. Therefore, TNM stage, microsatellite status, tumor grade, lymphovascular invasion, and other parameters are assessed in the pathology report to indicate the extent and prognosis of the disease. The mutation status of KRAS, BRAF, and NRAS is also investigated in a metastatic context to predict the response to anti-EGFR therapy...
February 7, 2018: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
Ewa Chmielik, Dagmara Rusinek, Malgorzata Oczko-Wojciechowska, Michal Jarzab, Jolanta Krajewska, Agnieszka Czarniecka, Barbara Jarzab
There are 5 main histological types of thyroid cancers (TCs): papillary, follicular (also known as differentiated), poorly differentiated, anaplastic (the most aggressive form), and medullary TC, and only the latter arises from thyroid C cells. These different forms of TCs show significant variability, both among and within tumours. This great variation is particularly notable among the first 4 types, which all originate from thyroid follicular cells. Importantly, this heterogeneity is not limited to histopathological diversity only but is also manifested as variation in several genetic and/or epigenetic alterations, the numbers of interactions between the tumour and surrounding microenvironment, and interpatient differences, for example...
February 6, 2018: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
Yuri Tolkach, Glen Kristiansen
Prostate cancer is a paradigm tumor model for heterogeneity in almost every sense. Its clinical, spatial, and morphological heterogeneity divided by the high-level molecular genetic diversity outline the complexity of this disease in the clinical and research settings. In this review, we summarize the main aspects of prostate cancer heterogeneity at different levels, with special attention given to the spatial heterogeneity within the prostate, and to the standard morphological heterogeneity, with respect to tumor grading and modern classifications...
January 31, 2018: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
Sonja Dulic, Zsofia Vasarhelyi, Anna Bajnok, Balazs Szalay, Gergely Toldi, Laszlo Kovacs, Attila Balog
OBJECTIVES: Ankylosing spondylitis (AS) is a chronic, progressive immune-mediated inflammatory disease, driven primarily by Th1 and Th17 cells. Anti-TNF therapies are successfully used in AS to achieve and maintain remission. However, their influence on the composition of T-cell subsets is not clear. We aimed to characterize the changes in the T-cell repertoire after a long-term anti-TNF treatment in AS patients. METHODS: Twenty-two AS patients under long-term anti-TNF therapy were evaluated (15 anti-TNF responders and 7 nonresponders)...
December 6, 2017: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
Martina Heller, Elena-Sophie Prigge, Adam Kaczorowski, Magnus von Knebel Doeberitz, Markus Hohenfellner, Stefan Duensing
BACKGROUND: APOBECs (apolipoprotein B mRNA-editing catalytic polypeptides) are cytidine deaminases that have been implicated in the host defense against viruses by blocking viral replication. They have also been shown to play a role in genome hypermutation in several human cancers. An APOBEC3 hypermutation signature has been discovered in cervical cancer, which is intimately associated with infection by high-risk human papillomaviruses (HPVs). At the same time, HPV genomes themselves are subject to DNA editing by APOBECs...
November 23, 2017: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
Thierry Habyarimana, Mohammed Attaleb, Pacifique Mugenzi, Jean Baptiste Mazarati, Youssef Bakri, Mohammed El Mzibri
BACKGROUND AND AIMS: A common polymorphism in the tumor suppressor gene p53 at codon 72 has been suggested to play a role in the development of a number of cancers. This polymorphism has been studied in many populations worldwide, with conflicting results. The present study was planned to assess the association of p53 codon 72 polymorphism with breast cancer development in a Rwandese population. METHODS: In this study, the polymorphism was examined by allele-specific PCR analysis in 40 patients with breast cancer and 39 healthy controls...
November 1, 2017: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
Naohide Oue, Yuji Yamamoto, Takashi Oshima, Ryuichi Asai, Akira Ishikawa, Naohiro Uraoka, Naoya Sakamoto, Kazuhiro Sentani, Wataru Yasui
OBJECTIVE: Spheroid colony formation is a useful method of cancer stem cell (CSC) characterization. We previously showed that the IQ motif containing the GTPase-activating protein 3 gene (IQGAP3) is upregulated in spheroid body-forming gastric cancer (GC) cells compared with parental cells. We investigated IQGAP3 expression in GC. METHODS: IQGAP3 protein expression was analyzed by immunohistochemistry in 165 GC cases. RNA interference was used to inhibit IQGAP3 expression in GC cell lines...
November 1, 2017: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
Mohammad Ilyas
Interrogation of tissue informs on patient management through delivery of a diagnosis together with associated clinically relevant data. The diagnostic pathologist will usually evaluate the morphological appearances of a tissue sample and, occasionally, the pattern of expression of a limited number of biomarkers. Recent developments in sequencing technology mean that DNA and RNA from tissue samples can now be interrogated in great detail. These new technologies, collectively known as next-generation sequencing (NGS), generate huge amounts of data which can be used to support patient management...
October 31, 2017: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
Myriam Kossaï, Alexandra Leary, Jean-Yves Scoazec, Catherine Genestie
Ovarian cancer encompasses a collection of neoplasms with distinct clinicopathological and molecular features and prognosis. Despite there being a variety of ovarian cancer subtypes, these are treated as a single disease. Tremendous efforts have been made to characterize these subtypes and identify tumoral pathways and potential biomarkers for therapeutic strategies. As in other cancer types, tumor heterogeneity appears to be very high across subtypes and within a single tumor, representing a major cause of treatment failure...
October 12, 2017: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
Eszter Csoma, László Bidiga, Gábor Méhes, Melinda Katona, Lajos Gergely
BACKGROUND/AIMS: The pathogenesis of the human polyomavirus (PyV) KI, WU, MW, and STL has not been elucidated yet. Respiratory transmission is suggested, but the site of the replication, tissue, and cell tropism is not clarified. KIPyV and WUPyV DNA and/or antigen were detected in normal lung tissues previously by others. In fact, a KIPyV DNA sequence was found in lung cancer samples. Up to date, there is no publication about the DNA prevalence of MWPyV and STLPyV neither in normal nor in cancerous lung tissues...
September 29, 2017: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
Miguel Rito, Isabel Fonseca
Salivary gland tumor classification encompasses a vast list of benign and malignant neoplasms. Their morphological diversity is recognized not only between different entities but also within individual tumors. Tumor categories as described by the World Health Organization reflect, in part, a true genetic heterogeneity (e.g., translocations involving CRTC1 and CRTC3-MAML2 genes in mucoepidermoid carcinoma and MYB-NFIB fusion in adenoid cystic carcinoma). Carcinoma ex pleomorphic adenoma shows diversity in its histological appearance, but recurrent rearrangements on PLAG1 and HMGA2 are common to its benign precursor...
September 21, 2017: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
Kinga Szurian, Karl Kashofer, Bernadette Liegl-Atzwanger
Bone and soft-tissue tumors are in general rare. Diagnosing these tumors is challenging based on the significant number of different tumor entities, the rareness of these tumors, and the considerable morphological heterogeneity which can be found within a single tumor entity. Considering that more than half of the described soft-tissue tumors and approximately 25% of the bone tumors harbor recurrent genetic alterations, the use of auxiliary molecular examinations should be strongly considered. Molecular analyses are important to confirm the diagnosis, to guide treatment, to provide information about prognosis, and to allow patient recruitment for basket trials based on the molecular signature of a tumor...
August 18, 2017: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
Jerome Cros, Jerome Raffenne, Anne Couvelard, Nicolas Poté
Pancreatic adenocarcinoma is one of the deadliest malignancies worldwide, mainly due to frequent diagnosis at an advanced stage and its strong chemoresistance. Tumor heterogeneity is evident at the histological level, both between tumors and even within a tumor. Recent high-throughput analyses have confirmed that intertumor heterogeneity is greater than intratumor heterogeneity that is mostly driven by successive catastrophic genetic events in the early stage and by epigenetic modifications in the metastatic stage...
August 5, 2017: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
Giorgio Stanta, Serena Bonin
This Pathobiology issue tries to better define the complex phenomenon of intratumor heterogeneity (ITH), mostly from a practical point of view. This topic has been chosen because ITH is a central issue in tumor development and has to be investigated directly in patient tissue and immediately applied in the treatment of the presenting patient. Different types of ITH should be considered: clonal genetic and epigenetic evolution, morphological heterogeneity, and tumor sampling, heterogeneity resulting from microenvironmental autocrine and paracrine interaction, and stochastic plasticity related to different functional cell efficiencies...
July 28, 2017: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
Christian M Schürch, Birgit Federmann, Leticia Quintanilla-Martinez, Falko Fend
The facts that cancer represents tissues consisting of heterogeneous neoplastic, as well as reactive, cell populations and that cancers of the same histotype may show profound differences in clinical behavior have long been recognized. With the advent of new technologies and the demands of precision medicine, the investigation of tumor heterogeneity has gained much interest. An understanding of intertumoral heterogeneity in patients with the same disease entity is necessary to optimally guide personalized treatment...
July 19, 2017: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
Irene Gullo, Fátima Carneiro, Carla Oliveira, Gabriela M Almeida
Gastric cancer (GC) represents a global health concern. Despite advances in prevention, diagnosis, and therapy, GC is still the third leading cause of cancer mortality worldwide, with more than 720,000 estimated deaths in 2012. Overall survival for advanced disease is about 1 year, a dismal prognosis that is partly due to the high levels of biological heterogeneity found in GC. Indeed, GC is a highly heterogeneous disease from morphological and molecular standpoints. The numerous histological and molecular classifications currently available reflect such heterogeneity...
June 16, 2017: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
Tiziana Venesio, Giulia Siravegna, Alberto Bardelli, Anna Sapino
Cancer is a spatial and temporal dynamic disease where differently evolving genetic clones are responsible for progression. In this landscape, the genomic heterogeneity of the primary tumours can be captured by deep-sequencing representative spatial samples. However, the recognition of genetic alterations responsible for tumour evolution remains a challenging task. Recently, the "liquid biopsy" was recognized as a powerful real-time approach for the molecular monitoring of this dynamic disease. The term "liquid biopsy" generally refers to the use of circulating (cell-free) tumour DNA (ctDNA) and circulating tumour cells (CTCs) as non-invasive biomarkers for the early diagnosis, prognosis, monitoring of clinical progression, and response to treatment in different types of tumours, including the highly genomic heterogeneous breast cancer...
June 15, 2017: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
Sònia Gatius, Dolors Cuevas, Carlos Fernández, Berta Roman-Canal, Virginia Adamoli, Josep Maria Piulats, Núria Eritja, Mireia Martin-Satue, Gema Moreno-Bueno, Xavier Matias-Guiu
Endometrial carcinoma (EC) shows intertumor heterogeneity, with several different histologic types differing in their morphologic and molecular features. There is also intratumoral morphologic heterogeneity, with different neoplastic cell components within the same tumor, with different morphologic and molecular features. In this article, we discuss the consequences of tumor heterogeneity in EC at the morphologic and molecular levels, by describing some illustrative examples produced by the research team. They are (1) morphologic heterogeneity in conventional EC and mixed tumors, (2) EC with microsatellite instability, (3) branched evolution as shown by exome sequencing analysis, (4) morphologic, molecular, and metabolomic differences between the tumor surface and myometrial invasion front, (5) tumor heterogeneity at the microenviromental level, (6) the sensitivity of endometrial aspirates to detect tumor heterogeneity in EC, and (7) sampling strategies to detect tumor heterogeneity in hysterectomy specimens...
June 15, 2017: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
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