دورية أكاديمية
أعرض في EDS

An integrated tool for determining the primary origin site of metastatic tumours.

التفاصيل البيبلوغرافية
العنوان: An integrated tool for determining the primary origin site of metastatic tumours.
المؤلفون: Santos MTD; ONKOS Molecular Diagnostics, Ribeirão Preto, São Paulo, Brazil.; Department of Research and Development (R&D), Fleury Group, Sao Paulo, Brazil., Souza BF; Federal University of Maranhão, UFMA, Sao Luis, Maranhão, Brazil., Cárcano FM; Department of Medical Oncology, Barretos Cancer Hospital, Barretos, Brazil., Vidal RO; Department of Research and Development (R&D), Fleury Group, Sao Paulo, Brazil.; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil., Scapulatempo-Neto C; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil., Viana CR; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil., Carvalho AL; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil.
المصدر: Journal of clinical pathology [J Clin Pathol] 2018 Jul; Vol. 71 (7), pp. 584-593. Date of Electronic Publication: 2017 Dec 16.
نوع المنشور: Journal Article; Validation Study
اللغة: English
بيانات الدورية: Publisher: BMJ Pub. Group Country of Publication: England NLM ID: 0376601 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1472-4146 (Electronic) Linking ISSN: 00219746 NLM ISO Abbreviation: J Clin Pathol Subsets: MEDLINE
أسماء مطبوعة: Publication: London : BMJ Pub. Group
Original Publication: London : British Medical Association
مواضيع طبية MeSH: Oligonucleotide Array Sequence Analysis* , Transcriptome*, Biomarkers, Tumor/*genetics , Gene Expression Profiling/*methods , Neoplasms, Unknown Primary/*genetics, Computational Biology ; Databases, Genetic ; Double-Blind Method ; Female ; Humans ; Male ; Neoplasms, Unknown Primary/classification ; Neoplasms, Unknown Primary/pathology ; Predictive Value of Tests ; Real-Time Polymerase Chain Reaction ; Reproducibility of Results ; Retrospective Studies ; Workflow
مستخلص: Aims: Cancers of unknown primary sites account for 3%-5% of all malignant neoplasms. Current diagnostic workflows based on immunohistochemistry and imaging tests have low accuracy and are highly subjective. We aim to develop and validate a gene-expression classifier to identify potential primary sites for metastatic cancers more accurately.
Methods: We built the largest Reference Database (RefDB) reported to date, composed of microarray data from 4429 known tumour samples obtained from 100 different sources and divided into 25 cancer superclasses formed by 58 cancer subclass. Based on specific profiles generated by 95 genes, we developed a gene-expression classifier which was first trained and tested by a cross-validation. Then, we performed a double-blinded retrospective validation study using a real-time PCR-based assay on a set of 105 metastatic formalin-fixed, paraffin-embedded (FFPE) samples. A histopathological review performed by two independent pathologists served as a reference diagnosis.
Results: The gene-expression classifier correctly identified, by a cross-validation, 86.6% of the expected cancer superclasses of 4429 samples from the RefDB, with a specificity of 99.43%. Next, the performance of the algorithm for classifying the validation set of metastatic FFPE samples was 83.81%, with 99.04% specificity. The overall reproducibility of our gene-expression-classifier system was 97.22% of precision, with a coefficient of variation for inter-assays and intra-assays and intra-lots <4.1%.
Conclusion: We developed a complete integrated workflow for the classification of metastatic tumour samples which may help on tumour primary site definition.
Competing Interests: Competing interests: MTdS holds equity at ONKOS Molecular Diagnostics but does not serve as a consultant or holds equity or equity options at Fleury Group. All other authors have no competing interests to declare.
(© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)
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فهرسة مساهمة: Keywords: cancer of unknown primary site; metastasis; molecular pathology
المشرفين على المادة: 0 (Biomarkers, Tumor)
تواريخ الأحداث: Date Created: 20171218 Date Completed: 20180730 Latest Revision: 20191210
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC6204949
DOI: 10.1136/jclinpath-2017-204887
PMID: 29248889
قاعدة البيانات: MEDLINE
الوصف
تدمد:1472-4146
DOI:10.1136/jclinpath-2017-204887