scholarly journals A Biphasic Pleural Tumor with Features of an Epithelioid and Small Cell Mesothelioma: Morphologic and Molecular Findings

2016 ◽  
Vol 2016 ◽  
pp. 1-10
Author(s):  
Sarah Hackman ◽  
Richard D. Hammer ◽  
Lester Layfield
Keyword(s):  
Abdominal Cavity ◽  
Molecular Genetic ◽  
Genetic Alterations ◽  
Small Cell ◽  
Comparative Genomic ◽  
Cell Nuclei ◽  
Pleural Tumor ◽  
Young Males ◽  
Round Cell Tumors

Malignant mesotheliomas are generally classified into epithelioid, sarcomatoid, desmoplastic, and biphasic types with rare reports of a small cell form. These small cell variants display some morphologic overlap with desmoplastic small round cell tumors (DSRCTs) which generally occur within the abdominal cavity of young males and are defined by a characteristic t(11;22)(p13;q12) translocation. However, there are rare reports of DSRCTs lacking this translocation. We present a 78-year-old man with a pleura-based biphasic neoplasm with features of both epithelioid mesothelioma and a small cell blastema-like neoplasm. The epithelioid portion showed IHC reactivity for pan cytokeratin, CK5/6, D2-40, and calretinin and the small cell portion marked with CD99, pan cytokeratin, WT1, FLI1, S100, CD200, MyoD1, and CD15. Fluorescence in situ hybridization testing for the t(11;22)(p13;q12) translocation disclosed loss of theEWSR1gene in 94% of tumor cell nuclei, but there was no evidence of the classic translocation. Array based-comparative genomic hybridization (a-CGH) confirmed the tumor had numerous chromosome copy number losses, including 11p15.5-p11.12 and 22q12.1-q13.33, with loss of theEWSR1andWT1gene regions. Herein, we report novel complex CGH findings in a biphasic tumor and review the molecular genetic alterations in both mesothelioma and DSRCTs.

Desmoplastic Small Round Cell Tumors With Atypical Presentations: A Report of 34 Cases

2018 ◽  
Vol 27 (3) ◽  
pp. 236-243 ◽  
Author(s):  
Alyaa Al-Ibraheemi ◽  
Cory Broehm ◽  
Munir R. Tanas ◽  
Andrew E. Horvai ◽  
Brian P. Rubin ◽  
...  
Keyword(s):  
Abdominal Cavity ◽  
Small Cell ◽  
Cell Tumor ◽  
Round Cell ◽  
Cell Sarcoma ◽  
Young Males ◽  
Small Round Cell ◽  
Atypical Presentations ◽  
Round Cell Tumors ◽  
Head Neck

Objectives. Desmoplastic small round cell tumor (DSRCT) is an aggressive round cell sarcoma that arises in the abdominal cavity/pelvis of young males. We sought to expand its clinicopathologic spectrum. Methods. Cases of DSRCT presenting in patients >30 years of age or tumors arising outside of the abdominal cavity/pelvis were retrieved. Results. Thirty-four cases were identified. Sixteen tumors arose at atypical sites (head/neck, intracranial, thigh, axilla/shoulder, inguinal/paratesticular, intraosseous, and uterine corpus). The remaining 18 patients were older than 30 years, and their tumors involved the abdomen or pelvis. The majority of cases showed areas with classic histology, while 6 cases exhibited solid growth and 5 showed macronodular architecture. Cytologic appearance included round cell, rhabdoid, epithelioid, and small cell. Conclusion. DSRCT may arise at nonabdominal locations in both pediatric and adult populations, as well as intra-abdominally in older adults, and these tumors exhibit high rates of metastasis and morbidity.

scholarly journals Biomarkers for ALK and ROS1 in Lung Cancer: Immunohistochemistry and Fluorescent In Situ Hybridization

2018 ◽  
Vol 142 (8) ◽  
pp. 922-928 ◽  
Author(s):  
Peter P. Luk ◽  
Christina I. Selinger ◽  
Annabelle Mahar ◽  
Wendy A. Cooper
Keyword(s):  
Lung Cancer ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Kinase Inhibitors ◽  
Screening Method ◽  
Genetic Alterations ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lung Cancers

Context.— A small proportion of non–small cell lung cancers harbor rearrangements of ALK or ROS1 genes, and these tumors are sensitive to targeted tyrosine kinase inhibitors. It is crucial for pathologists to accurately identify tumors with these genetic alterations to enable patients to access optimal treatments and avoid unnecessary side effects of less effective agents. Although a number of different techniques can be used to identify ALK- and ROS1-rearranged lung cancers, immunohistochemistry and fluorescence in situ hybridization are the mainstays. Objective.— To review the role of immunohistochemistry in assessment of ALK and ROS1 rearrangements in lung cancer, focusing on practical issues in comparison with other modalities such as fluorescence in situ hybridization. Data Sources.— This manuscript reviews the current literature on ALK and ROS1 detection using immunohistochemistry and fluorescence in situ hybridization as well as current recommendations. Conclusions.— Although fluorescence in situ hybridization remains the gold standard for detecting ALK and ROS1 rearrangement in non–small cell lung cancer, immunohistochemistry plays an important role and can be an effective screening method for detection of these genetic alterations, or a diagnostic test in the setting of ALK.

scholarly journals Detection and Correlation of Single and Concomitant TP53, PTEN, and CDKN2A Alterations in Gliomas

2019 ◽  
Vol 20 (11) ◽  
pp. 2658 ◽  
Author(s):  
Igor Andrade Pessôa ◽  
Carolina Koury Amorim ◽  
Wallax Augusto Silva Ferreira ◽  
Fernanda Sagica ◽  
José Reginaldo Brito ◽  
...  
Keyword(s):  
Tumor Suppressor Genes ◽  
Genetic Alterations ◽  
Comparative Genomic ◽  
Low Grade ◽  
Heterozygous Deletion ◽  
Single Strand Conformational Polymorphism ◽  
Primary Tumors ◽  
Tumor Subtypes ◽  
Frequent Event

Gliomas are the most frequent primary tumors of central nervous system and represent a heterogeneous group of tumors that originates from the glial cells. TP53, PTEN, and CDKN2A are important tumor suppressor genes that encode proteins involved in sustaining cellular homeostasis by different signaling pathways. Though genetic alterations in these genes play a significant role in tumorigenesis, few studies are available regarding the incidence and relation of concomitant TP53, PTEN, and CDKN2A alterations in gliomas. The purpose of this study was to evaluate the occurrence of mutation and deletion in these genes, through single-strand conformational polymorphism, array-comparative genomic hybridization, and fluorescence in situ hybridization techniques, in 69 gliomas samples. Molecular results demonstrated a significant higher prevalence of TP53, PTEN, and CDKN2A alterations in astrocytoma than other tumor subtypes, and heterozygous deletion was the most frequent event. In addition, a significant association was observed between TP53 and CDKN2A alterations (p = 0.0424), which tend to coexist in low grade astrocytomas (5/46 cases (10.9%)), suggesting that they are early events in development of these tumors, and PTEN and CDKN2A deletions (p = 0.0022), which occurred concomitantly in 9/50 (18%) patients, with CDKN2A changes preceding PTEN deletions, present preferably in high-grade gliomas.

scholarly journals Genetic Alterations in Presumptive Precursor Lesions of Breast Carcinomas

2002 ◽  
Vol 24 (2-3) ◽  
pp. 69-76 ◽  
Author(s):  
Michaela Aubele ◽  
Martin Werner ◽  
Heinz Höfler
Keyword(s):  
Ductal Carcinoma ◽  
Early Stage ◽  
Dna Amplification ◽  
Genetic Alterations ◽  
Molecular Genetic Analysis ◽  
Premalignant Lesions ◽  
Comparative Genomic ◽  
Precursor Lesions ◽  
Normal Epithelium

The hypothetical multistep model of breast carcinogenesis suggests a transition from normal epithelium to invasive carcinoma via intraductal hyperplasia (without and with atypia) andin situcarcinoma. These presumptive precursor lesions are currently defined by their histological features, and their prognosis is imprecisely estimated from indirect epidemiological evidence. Cytogenetic and molecular‐genetic analysis of these lesions give evidence for an accumulation of various genetic alterations during breast tumorigenesis. Using immuno‐histochemistry overexpression of the c‐erbB‐2 oncogene was found in ductal carcinomain situ(DCIS), but not in atypical intraductal hyperplasia (AIDH) and intraductal hyperplasia (IDH). An expression of mutant p53 tumor suppressor gene as well as expression of cyclin D1 was identified in DCIS. In IDH lesions loss of heterozygosity (LOH) at various loci could be identified, and comparative genomic hybridization (CGH) and fluorescencein situhybridization (FISH) studies delivered evidence for DNA amplification on chromosomal region 20q13 in the early stage of IDH. However, little is currently known about genetic alterations in those premalignant lesions, and the chronology of genetic alterations and histopathological changes during carcinogenesis is mainly undiscovered. Figure 1 can be viewed in colour onhttp://www.esacp.org/acp/2002/24‐23/aubele.htm

Genetic alterations in a papillary glioneuronal tumor

2008 ◽  
Vol 1 (1) ◽  
pp. 99-102 ◽  
Author(s):  
Claudia Faria ◽  
José Miguéns ◽  
João Lobo Antunes ◽  
Cândida Barroso ◽  
José Pimentel ◽  
...  
Keyword(s):  
Genetic Alterations ◽  
Point Of View ◽  
Chromosome 7 ◽  
Glioneuronal Tumor ◽  
Comparative Genomic ◽  
Low Grade ◽  
The Central Nervous System ◽  
High Level ◽  
Glioneuronal Tumors

✓Papillary glioneuronal tumors (PGNTs) are rare lesions of the central nervous system, and no information exists on the genetic alterations in these neoplasms. The authors report on such a case in a child. Genetic studies revealed that the tumor was characterized by gains and structural alterations involving only chromosome 7 with breakpoints at 7p22. By using comparative genomic hybridization, the authors observed a high-level amplification region at 7p14~q12. Fluorescence in situ hybridization with a probe for EGFR revealed that this gene was not amplified. Similar to other patients with PGNTs, the patient in the present case fared well. From a genetic point of view the data in the present case are in accordance with previous findings of EGFR amplifications as uncommon in low-grade gliomas and gangliogliomas. Recurrent rearrangements of chromosome 7 have been noted in other mixed glioneuronal tumors. The data in this case suggest that genes located at chromosome 7 can also be involved in the pathogenesis of PGNT. In clinical terms it will be especially important to corroborate, through the analysis of further cases, the involvement of the chromosome 7p22 locus, a region where glial and neuronal linked genes (RAC1 and NXPH1) are known to be located.

GENETIC ALTERATIONS IN CARCINOMAS IN SITU OF THE BLADDER BY COMPARATIVE GENOMIC HYBRIDIZATION

1999 ◽  
pp. 117
Author(s):  
Regina M. Hovey ◽  
Lynn Bjerke ◽  
Lucy Epstein ◽  
Michael Muscheck ◽  
Vivek Barghava ◽  
...  
Keyword(s):  
Comparative Genomic Hybridization ◽  
Genetic Alterations ◽  
Comparative Genomic ◽  
Genomic Hybridization

scholarly journals Alteredp16INK4and RB1 Expressions Are Associated with Poor Prognosis in Patients with Nonsmall Cell Lung Cancer

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Weiqiang Zhao ◽  
Cheng C. Huang ◽  
Gregory A. Otterson ◽  
Marino E. Leon ◽  
Yan Tang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Cells ◽  
Cell Lung Cancer ◽  
Molecular Genetic ◽  
Nonsmall Cell Lung Cancer ◽  
Genetic Alterations ◽  
Adverse Outcomes ◽  
Cell Cycle Regulators ◽  
Functional Inactivation

p16INK4and RB1 are two potent cell cycle regulators to control the G1/S transition by interacting with CDK4/6, E2F, and D-type cyclins, respectively. Depending on the tumour type, genetic alterations resulting in the functional inactivation have frequently been reported in both genes. By contrast, much less is known regarding the overexpression of these proteins in the tumor cells. In this study, expressions of p16INK4RB1, andCDKN2Acopy number variances (CNV) in the tumor cells were assessed by immunohistochemistry and fluorescence in situ hybridization (FISH), respectively, in 73 nonsmall cell lung cancer (NSCLC) with known 5-year survivals. The histologic type (P=0.01), p16INK4(P=0.004), and RB1 (P<0.001) were predictive of survivals. TheCDKN2ACNV (P<0.05) was also significant when compared to those cases without CNV. Therefore, among the molecular genetic prognostic factors, expressions of RB1 and p16INK4in the tumor cells were the most strongly predictive of adverse outcomes in stage I and II nonsquamous NSCLC.

High performance Nanogold™-in situ hybridzation and its use in the detection of hybridized and PCR-amplified microscopical preparations

1996 ◽  
Vol 54 ◽  
pp. 896-897
Author(s):  
G. W. Hacker ◽  
I. Zehbe ◽  
J. Hainfeld ◽  
A.-H. Graf ◽  
C. Hauser-Kronberger ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Messenger Rna ◽  
High Performance ◽  
Detection System ◽  
Direct Methods ◽  
Genetic Alterations ◽  
Chain Reaction ◽  
Protein Encoding ◽  
Polymerase Chain

In situ hybridization (ISH) with biotin-labeled probes is increasingly used in histology, histopathology and molecular biology, to detect genetic nucleic acid sequences of interest, such as viruses, genetic alterations and peptide-/protein-encoding messenger RNA (mRNA). In situ polymerase chain reaction (PCR) (PCR in situ hybridization = PISH) and the new in situ self-sustained sequence replication-based amplification (3SR) method even allow the detection of single copies of DNA or RNA in cytological and histological material. However, there is a number of considerable problems with the in situ PCR methods available today: False positives due to mis-priming of DNA breakdown products contained in several types of cells causing non-specific incorporation of label in direct methods, and re-diffusion artefacts of amplicons into previously negative cells have been observed. To avoid these problems, super-sensitive ISH procedures can be used, and it is well known that the sensitivity and outcome of these methods partially depend on the detection system used.

Molecular genetic markers for thyroid FNAB

2015 ◽  
Vol 54 (03) ◽  
pp. 94-100 ◽  
Author(s):  
P. B. Musholt ◽  
T. J. Musholt
Keyword(s):  
Genetic Markers ◽  
Thyroid Nodules ◽  
Molecular Genetic ◽  
Genetic Alterations ◽  
Diagnostic Tools ◽  
Ultrasound Screening ◽  
Thyroid Malignancy ◽  
Thyroid Carcinomas ◽  
Molecular Genetic Markers ◽  
The Impact

SummaryAim: Thyroid nodules > 1 cm are observed in about 12% of unselected adult employees aged 18–65 years screened by ultrasound scan (40). While intensive ultrasound screening leads to early detection of thyroid diseases, the determination of benign or malignant behaviour remains uncertain and may trigger anxieties in many patients and their physicians. A considerable number of thyroid resections are consecutively performed due to suspicion of malignancy in the detected nodes. Fine needle aspiration biopsy (FNAB) has been recommended for the assessment of thyroid nodules to facilitate detection of thyroid carcinomas but also to rule out malignancy and thereby avoid unnecessary thyroid resections. However, cytology results are dependent on experience of the respective cytologist and unfortunately inconclusive in many cases. Methods: Molecular genetic markers are already used nowadays to enhance sensitivity and specificity of FNAB cytology in some centers in Germany. The most clinically relevant molecular genetic markers as pre-operative diagnostic tools and the clinical implications for the intraoperative and postoperative management were reviewed. Results: Molecular genetic markers predominantly focus on the preoperative detection of thyroid malignancies rather than the exclusion of thyroid carcinomas. While some centers routinely assess FNABs, other centers concentrate on FNABs with cytology results of follicular neoplasia or suspicion of thyroid carcinoma. Predominantly mutations of BRAF, RET/PTC, RAS, and PAX8/PPARγ or expression of miRNAs are analyzed. However, only the detection of BRAF mutations predicts the presence of (papillary) thyroid malignancy with almost 98% probability, indicating necessity of oncologic thyroid resections irrespective of the cytology result. Other genetic alterations are associated with thyroid malignancy with varying frequency and achieve less impact on the clinical management. Conclusion: Molecular genetic analysis of FNABs is increasingly performed in Germany. Standardization, quality controls, and validation of various methods need to be implemented in the near future to be able to compare the results. With increasing knowledge about the impact of genetic alterations on the prognosis of thyroid carcinomas, recommendations have to be defined that may lead to individually optimized treatment strategies.

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