Diagnosis of metastatic neoplasms: molecular approaches for identification of tissue of origin.
ABSTRACT Tumors of uncertain or unknown origin are estimated to constitute 3% to 5% of all metastatic cancer cases. Patients with these types of tumors show worse outcomes when compared to patients in which a primary tumor is identified. New molecular tests that identify molecular signatures of a tissue of origin have become available.
To review the literature on existing molecular approaches to the diagnosis of metastatic tumors of uncertain origin and discuss the current status and future developments in this area.
Published peer-reviewed literature, available information from medical organizations (National Comprehensive Cancer Network), and other publicly available information from tissue-of-origin test providers and/or manufacturers.
Molecular tests for tissue-of-origin determination in metastatic tumors are available and have the potential to significantly impact patient management. However, available validation data indicate that not all tests have shown adequate performance characteristics for clinical use. Pathologists and oncologists should carefully evaluate claims for accuracy and clinical utility for tissue-of-origin tests before using test results in patient management. The personalized medicine revolution includes the use of molecular tools for identification/confirmation of the site of origin for metastatic tumors, and in the future, this strategy might also be used to determine specific therapeutic approaches.
SourceAvailable from: unknownprimarycancers.com
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ABSTRACT: Cancer of unknown primary (CUP) is a well recognized clinical syndrome, accounting for 3-5% of all malignancies. It is characterized as a disease with an early dissemination of metastases without a primary detected site after extensive laboratory and clinical investigations. CUP is divided into the favorable and unfavorable groups based on histopathological and clinical manifestations. Adenocarcinoma of various differentiation is the commonest histopathological subtype. Favorable groups are treated with local or systemic treatment and some of them are enjoying long-term survival. On the contrary, unfavorable groups are treated with empirical chemotherapy having usually a dismal prognosis. Gene-profiling microarray diagnosis has a high diagnostic sensitivity, but its predictive or prognostic value remains uncertain.Journal of Advanced Research 11/2014; DOI:10.1016/j.jare.2014.11.007
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ABSTRACT: BACKGROUND The workup of a malignant effusion usually requires immunostaining with a panel of markers. Although nuclear Wilms tumor 1 (WT1) expression is widely used to detect tumors of ovarian and mesothelial origin, it is less well known that WT1 is also expressed in the cytoplasm of melanomas and mesenchymal tumors. Because to the authors' knowledge the diagnostic utility of cytoplasmic WT1 expression has not been explored to date, the usefulness of a WT1/AE1/AE3 dual-color immunostain in the workup of malignant effusions was evaluated.METHODSA total of 86 pleural effusions, including 17 metastatic melanomas, 31 metastatic adenocarcinomas, 10 malignant mesotheliomas, 10 lymphoproliferative disorders, 5 metastatic sarcomas, and 13 benign specimens, were immunostained using a peroxidase-based brown chromogen for WT1 and an alkaline phosphatase-based red chromogen for AE1/AE3 on cell block sections.RESULTSThe majority of malignant effusions stained in 1 of 4 distinctive patterns: 1) all lung and breast adenocarcinomas demonstrated cytoplasmic AE1/AE3 expression without nuclear or cytoplasmic WT1 expression; 2) serous carcinomas of Müllerian origin, mesotheliomas, and benign mesothelial cells were positive for cytoplasmic AE1/AE3 as well as nuclear WT1; 3) melanomas, sarcomas, and a subset of plasma cell neoplasms were positive for cytoplasmic expression of WT1 but negative for AE1/AE3; and 4) large B-cell lymphomas and a subset of plasma cell neoplasms were negative for both markers.CONCLUSIONSA WT1/AE1/AE3 dual-color immunostain can reliably identify malignancy in pleural effusions and group malignant cells into discrete subsets, thereby narrowing the differential diagnosis. This simple double stain can be a cost-effective, first-line test in the workup of patients with malignant effusions. Cancer (Cancer Cytopathol) 2014. © 2014 American Cancer Society.Cancer Cytopathology 08/2014; 122(8). DOI:10.1002/cncy.21439 · 3.81 Impact Factor