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  • 1
    Online Resource
    Online Resource
    "Spot 14" Protein: A Metabolic Integrator in Normal and Neoplastic Cells
    Mary Ann Liebert Inc ; 1998
    In:  Thyroid Vol. 8, No. 9 ( 1998-09), p. 815-825
    Details
    In: Thyroid, Mary Ann Liebert Inc, Vol. 8, No. 9 ( 1998-09), p. 815-825
    Type of Medium: Online Resource
    ISSN: 1050-7256 , 1557-9077
    URL: Article
    DOI: 10.1089/thy.1998.8.815
    Language: English
    Publisher: Mary Ann Liebert Inc
    Publication Date: 1998
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  • 2
    Online Resource
    Online Resource
    The “Spot 14” gene resides on the telomeric end of the 11q13 amplicon and is expressed in lipogenic breast cancers: Implications for control of tumor metabolism
    Proceedings of the National Academy of Sciences ; 1998
    In:  Proceedings of the National Academy of Sciences Vol. 95, No. 12 ( 1998-06-09), p. 6989-6994
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 95, No. 12 ( 1998-06-09), p. 6989-6994
    Abstract: Enhanced long chain fatty acid synthesis may occur in breast cancer, where it is necessary for tumor growth and predicts a poor prognosis. “Spot 14” (S14) is a carbohydrate- and thyroid hormone-inducible nuclear protein specific to liver, adipose, and lactating mammary tissues that functions to activate genes encoding the enzymes of fatty acid synthesis. Amplification of chromosome region 11q13, where the S14 gene ( THRSP ) resides, also predicts a poor prognosis in breast tumors. We localized the S14 gene between markers D11S906 and D11S937, at the telomeric end of the amplified region at 11q13, and found that it was amplified and expressed in breast cancer-derived cell lines. Moreover, concordant expression of S14 and a key lipogenic enzyme (acetyl-CoA carboxylase) in a panel of primary breast cancer specimens strongly supported a role for S14 as a determinant of tumor lipid metabolism. S14 expression provides a pathophysiological link between two prognostic indicators in breast cancer: enhanced lipogenesis and 11q13 amplification.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.95.12.6989
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 1998
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    SSG: 11
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    31. The PT alphabet soup: LDT, FDA, NGS, non-NGS, @#$!%
    Elsevier BV ; 2019
    In:  Cancer Genetics Vol. 233-234 ( 2019-04), p. S13-
    Details
    In: Cancer Genetics, Elsevier BV, Vol. 233-234 ( 2019-04), p. S13-
    Type of Medium: Online Resource
    ISSN: 2210-7762
    URL: Article
    DOI: 10.1016/j.cancergen.2019.04.037
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2019
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  • 4
    Online Resource
    Online Resource
    Abstract 797: Cancers of unknown primary: A descriptive study in the U.S. military health system
    American Association for Cancer Research (AACR) ; 2021
    In:  Cancer Research Vol. 81, No. 13_Supplement ( 2021-07-01), p. 797-797
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 81, No. 13_Supplement ( 2021-07-01), p. 797-797
    Abstract: Background: Cancers of unknown primary (CUP) are defined as histologically confirmed metastatic cancers that do not have an identified primary site of origin despite an appropriate diagnostic work-up. It is known that accessibility to and quality of medical care are associated with cancer diagnosis. This study aimed to describe the demographic, histologic, and temporal trend characteristics of CUP patients in the Military Health System (MHS), which provides universal healthcare access. Methods: The data were obtained from the Department of Defense (DoD)'s Automated Tumor Registry (ACTUR) which collects cancer data from beneficiaries who were diagnosed or received treatment in the (MHS). We described the demographic and histologic distributions in CUP patients aged 18 or older diagnosed from 1987-2013. We calculated the proportion of CUP patients among all metastatic cancers and the most common histologic categories of those tumors. We then evaluated whether the proportion of histologic types changed over time. Results: CUP comprised 15.1% of all metastatic cancers in ACTUR during the study period. The majority of CUP within ACTUR was well and moderately differentiated adenocarcinoma (51.3%) and poorly differentiated carcinomas (23.2%) followed by squamous cell carcinomas (12.5%). The percentages of CUP among metastasized cancers of the same histologic category ranged 12-15% for well and moderately differentiated adenocarcinomas, squamous cell, and poorly differentiated carcinomas, and 41-46% for malignant neuroendocrine carcinomas and undifferentiated neoplasms. However, the percentages varied by sex, race, and age for certain pathologies. The proportion of CUP patients among all metastatic cancer patients has steadily declined from 22.4% to 8.3% from 1987 to 2013. Conclusion: The proportion and trends of CUP in the MHS were generally consistent with other descriptive CUP studies. This study provides a description of CUP in a healthcare system with universal access and provides a foundation for future studies on CUP. Citation Format: Julie A. Bytnar, Jie Lin, Joel T. Moncur, Craig D. Shriver, Kangmin Zhu. Cancers of unknown primary: A descriptive study in the U.S. military health system [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 797.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2021-797
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
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    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 5
    Online Resource
    Online Resource
    Comparison of Laboratory-Developed Tests and FDA-Approved Assays for BRAF, EGFR, and KRAS Testing
    American Medical Association (AMA) ; 2018
    In:  JAMA Oncology Vol. 4, No. 6 ( 2018-06-01), p. 838-
    Details
    In: JAMA Oncology, American Medical Association (AMA), Vol. 4, No. 6 ( 2018-06-01), p. 838-
    Type of Medium: Online Resource
    ISSN: 2374-2437
    URL: Article
    DOI: 10.1001/jamaoncol.2017.4021
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2018
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  • 6
    Online Resource
    Online Resource
    Proficiency Testing of Standardized Samples Shows High Interlaboratory Agreement for Clinical Next-Generation Sequencing–Based Hematologic Malignancy Assays With Survey Material–Specific Differences in Variant Frequencies
    Archives of Pathology and Laboratory Medicine ; 2020
    In:  Archives of Pathology & Laboratory Medicine Vol. 144, No. 8 ( 2020-08-01), p. 959-966
    Details
    In: Archives of Pathology & Laboratory Medicine, Archives of Pathology and Laboratory Medicine, Vol. 144, No. 8 ( 2020-08-01), p. 959-966
    Abstract: As laboratories increasingly turn from single-analyte testing in hematologic malignancies to next-generation sequencing–based panel testing, there is a corresponding need for proficiency testing to ensure adequate performance of these next-generation sequencing assays for optimal patient care. Objective.— To report the performance of laboratories on proficiency testing from the first 4 College of American Pathologists Next-Generation Sequencing Hematologic Malignancy surveys. Design.— College of American Pathologists proficiency testing results for 36 different engineered variants and/or allele fractions as well as a sample with no pathogenic variants were analyzed for accuracy and associated assay performance characteristics. Results.— The overall sensitivity observed for all variants was 93.5% (2190 of 2341) with 99.8% specificity (22 800 of 22 840). The false-negative rate was 6.5% (151 of 2341), and the largest single cause of these errors was difficulty in identifying variants in the sequence of CEBPA that is rich in cytosines and guanines. False-positive results (0.18%; 40 of 22 840) were most likely the result of preanalytic or postanalytic errors. Interestingly, the variant allele fractions were almost uniformly lower than the engineered fraction (as measured by digital polymerase chain reaction). Extensive troubleshooting identified a multifactorial cause for the low variant allele fractions, a result of an interaction between the linearized nature of the plasmid and the Illumina TruSeq chemistry. Conclusions.— Laboratories demonstrated an overall accuracy of 99.2% (24 990 of 25 181) with 99.8% specificity and 93.5% sensitivity when examining 36 clinically relevant somatic single-nucleotide variants with a variant allele fraction of 10% or greater. The data also highlight an issue with artificial linearized plasmids as survey material for next-generation sequencing.
    Type of Medium: Online Resource
    ISSN: 0003-9985 , 1543-2165
    URL: Article
    DOI: 10.5858/arpa.2019-0352-CP
    RVK:
    XA 10000
    RVK:
    XA 29700
    Language: English
    Publisher: Archives of Pathology and Laboratory Medicine
    Publication Date: 2020
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  • 7
    Online Resource
    Online Resource
    Neoplastic Cellularity Assessment in Molecular Testing
    Archives of Pathology and Laboratory Medicine ; 2022
    In:  Archives of Pathology & Laboratory Medicine Vol. 146, No. 9 ( 2022-09-01), p. 1062-1071
    Details
    In: Archives of Pathology & Laboratory Medicine, Archives of Pathology and Laboratory Medicine, Vol. 146, No. 9 ( 2022-09-01), p. 1062-1071
    Abstract: Neoplastic cellularity assessment has become an essential component of molecular oncology testing; however, there are currently no best practice recommendations or guidelines for this potentially variable step in the testing process. Objective.— To describe the domestic and international practices of neoplastic cellularity assessment and to determine how variations in laboratory practices affect neoplastic cellularity assessment accuracy. Design.— Data were derived from 57 US and international laboratories that participated in the 2019 College of American Pathologists Neoplastic Cellularity Proficiency Testing Survey (NEO-B 2019). NEO-B 2019 included 29 laboratory practice questions and 5 images exhibiting challenging histologic features. Participants assessed the neoplastic cellularity of hematoxylin-eosin–stained digital images, and results were compared to a criterion standard derived from a manual cell count. Results.— The survey responses showed variations in the laboratory practices for the assessment of neoplastic cellularity, including the definition of neoplastic cellularity, assessment methodology, counting practices, and quality assurance practices. In some instances, variation in laboratory practice affected neoplastic cellularity assessment performance. Conclusions.— The results highlight the need for a consensus definition and improved standardization of the assessment of neoplastic cellularity. We put forth an initial set of best practice recommendations to begin the process of standardizing neoplastic cellularity assessment.
    Type of Medium: Online Resource
    ISSN: 1543-2165 , 0003-9985
    URL: Article
    DOI: 10.5858/arpa.2021-0166-CP
    RVK:
    XA 10000
    RVK:
    XA 29700
    Language: English
    Publisher: Archives of Pathology and Laboratory Medicine
    Publication Date: 2022
    detail.hit.zdb_id: 2028916-9
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  • 8
    Online Resource
    Online Resource
    Cancers of Unknown Primary: A Descriptive Study in the U.S. Military Health System
    Oxford University Press (OUP) ; 2023
    In:  Military Medicine Vol. 188, No. 3-4 ( 2023-03-20), p. e516-e523
    Details
    In: Military Medicine, Oxford University Press (OUP), Vol. 188, No. 3-4 ( 2023-03-20), p. e516-e523
    Abstract: Cancers of unknown primary (CUP) are defined as histologically confirmed metastatic cancers that do not have an identified primary site of origin despite an appropriate diagnostic workup. Although accessibility to and quality of medical care influence diagnosis of cancer including CUP, previous studies describing CUP have generally been conducted in patients with various accessibilities to care. This study aimed to describe the demographic, histologic, and temporal trend characteristics of CUP patients in the DoD Cancer Registry of the Military Health System (MHS), which provides universal health care access, reducing the potential effects of accessibility to care on research results. Materials and Methods The data were obtained from the DoD’s Automated Central Tumor Registry (ACTUR), which collects cancer data from beneficiaries who were diagnosed or received treatment in the MHS. We described the demographic and histologic distributions in CUP patients aged 18 years or older diagnosed from 1987 to 2013. We calculated the proportion of CUP patients among all metastatic cancers and the most common histologic categories of those tumors. We then evaluated whether the proportion of histologic types changed over time. Results CUP comprised 13.3% of all metastatic cancers in ACTUR during the study period. The majority of CUP within ACTUR was moderately and well-differentiated adenocarcinoma (51.3%) and poorly differentiated carcinomas (23.2%) followed by squamous cell carcinomas (12.5%). The percentages of CUP among metastasized cancers of the same histologic category ranged 12%-15% for moderately and well-differentiated adenocarcinomas, squamous cell, and poorly differentiated carcinomas, and 41%-46% for malignant neuroendocrine carcinomas and undifferentiated neoplasms. However, the percentages varied by sex, race, and age for certain pathologies. The proportion of CUP patients among all metastatic cancer patients has steadily declined from 22.4% to 8.3% from 1987 to 2013. Conclusion The proportion and trends of CUP in the ACTUR were generally consistent with other descriptive CUP studies. This study provides a description of CUP in a health care system with universal access in the USA and provides a foundation for future studies on CUP.
    Type of Medium: Online Resource
    ISSN: 0026-4075 , 1930-613X
    URL: Article
    DOI: 10.1093/milmed/usab291
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
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  • 9
    Online Resource
    Online Resource
    The Reemergence of Measles
    Oxford University Press (OUP) ; 2023
    In:  American Journal of Clinical Pathology Vol. 159, No. 1 ( 2023-01-04), p. 81-88
    Details
    In: American Journal of Clinical Pathology, Oxford University Press (OUP), Vol. 159, No. 1 ( 2023-01-04), p. 81-88
    Abstract: Present-day pathologists may be unfamiliar with the histopathologic features of measles, which is a reemerging disease. Awareness of these features may enable early diagnosis of measles in unsuspected cases, including those with an atypical presentation. Using archived tissue samples from historic patients, a unique source of histopathologic information about measles and other reemerging infectious diseases, we performed a comprehensive analysis of the histopathologic features of measles seen in commonly infected tissues during prodrome, active, and late phases of the disease. Methods Subspecialty pathologists analyzed H & E-stained slides of specimens from 89 patients accessioned from 1919 to 1998 and correlated the histopathologic findings with clinical data. Results Measles caused acute and chronic histopathologic changes, especially in the respiratory, lymphoid (including appendix and tonsils), and central nervous systems. Bacterial infections in lung and other organs contributed significantly to adverse outcomes, especially in immunocompromised patients. Conclusions Certain histopathologic features, especially Warthin-Finkeldey cells and multinucleated giant cells without inclusions, allow pathologists to diagnose or suggest the diagnosis of measles in unsuspected cases.
    Type of Medium: Online Resource
    ISSN: 0002-9173 , 1943-7722
    URL: Article
    DOI: 10.1093/ajcp/aqac124
    RVK:
    YV 2000
    RVK:
    XA 18700
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2039921-2
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  • 10
    Online Resource
    Online Resource
    Neurovascular injury with complement activation and inflammation in COVID-19
    Oxford University Press (OUP) ; 2022
    In:  Brain Vol. 145, No. 7 ( 2022-07-29), p. 2555-2568
    Details
    In: Brain, Oxford University Press (OUP), Vol. 145, No. 7 ( 2022-07-29), p. 2555-2568
    Abstract: The underlying mechanisms by which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to acute and long-term neurological manifestations remains obscure. We aimed to characterize the neuropathological changes in patients with coronavirus disease 2019 and determine the underlying pathophysiological mechanisms. In this autopsy study of the brain, we characterized the vascular pathology, the neuroinflammatory changes and cellular and humoral immune responses by immunohistochemistry. All patients died during the first wave of the pandemic from March to July 2020. All patients were adults who died after a short duration of the infection, some had died suddenly with minimal respiratory involvement. Infection with SARS-CoV-2 was confirmed on ante-mortem or post-mortem testing. Descriptive analysis of the pathological changes and quantitative analyses of the infiltrates and vascular changes were performed. All patients had multifocal vascular damage as determined by leakage of serum proteins into the brain parenchyma. This was accompanied by widespread endothelial cell activation. Platelet aggregates and microthrombi were found adherent to the endothelial cells along vascular lumina. Immune complexes with activation of the classical complement pathway were found on the endothelial cells and platelets. Perivascular infiltrates consisted of predominantly macrophages and some CD8+ T cells. Only rare CD4+ T cells and CD20+ B cells were present. Astrogliosis was also prominent in the perivascular regions. Microglial nodules were predominant in the hindbrain, which were associated with focal neuronal loss and neuronophagia. Antibody-mediated cytotoxicity directed against the endothelial cells is the most likely initiating event that leads to vascular leakage, platelet aggregation, neuroinflammation and neuronal injury. Therapeutic modalities directed against immune complexes should be considered.
    Type of Medium: Online Resource
    ISSN: 0006-8950 , 1460-2156
    URL: Article
    DOI: 10.1093/brain/awac151
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 1474117-9
    SSG: 12
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