Overview of Patient Management and Future Directions in Unknown Primary Carcinoma

Varadhachary, Gauri R.; Greco, F. Anthony

doi:10.1053/j.seminoncol.2008.10.008

Cited by 24 publications

(21 citation statements)

References 18 publications

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“…[1][2][3] This process can delay initiation of treatment; more importantly, without identification of the primary tumor, an appropriate therapeutic plan cannot be created. [4][5][6][7] The application of molecular diagnostics to the identification of tumor tissue of origin has received substantial recent attention. [8][9][10][11][12] Most studies of molecular diagnosis of tissue of origin used messenger RNA (mRNA) profiling of tumor samples.…”

mentioning

confidence: 99%

Validation of a microRNA-based qRT-PCR test for accurate identification of tumor tissue origin

et al. 2010

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Identification of the tissue of origin of a tumor is vital to its management. Previous studies showed tissuespecific expression patterns of microRNA and suggested that microRNA profiling would be useful in addressing this diagnostic challenge. MicroRNAs are well preserved in formalin-fixed, paraffin-embedded (FFPE) samples, further supporting this approach. To develop a standardized assay for identification of the tissue origin of FFPE tumor samples, we used microarray data from 504 tumor samples to select a shortlist of 104 microRNA biomarker candidates. These 104 microRNAs were profiled by proprietary quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) on 356 FFPE tumor samples. A total of 48 microRNAs were chosen from this list of candidates and used to train a classifier. We developed a clinical test for the identification of the tumor tissue of origin based on a standardized protocol and defined the classification criteria. The test measures expression levels of 48 microRNAs by qRT-PCR, and predicts the tissue of origin among 25 possible classes, corresponding to 17 distinct tissues and organs. The biologically motivated classifier combines the predictions generated by a binary decision tree and K-nearest neighbors (KNN). The classifier was validated on an independent, blinded set of 204 FFPE tumor samples, including nearly 100 metastatic tumor samples. The test predictions correctly identified the reference diagnosis in 85% of the cases. In 66% of the cases the two algorithm predictions (tree and KNN) agreed on a single-tissue origin, which was identical to the reference diagnosis in 90% of cases. Thus, a qRT-PCR test based on the expression profile of 48 tissue-specific microRNAs allows accurate identification of the tumor tissue of origin.

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confidence: 99%

Validation of a microRNA-based qRT-PCR test for accurate identification of tumor tissue origin

et al. 2010

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“…27,28 In patients with occult primary tumors, immunohistochemical markers are useful for cell-type determination and pathologic diagnosis. 29,30 Because immunohistochemistry markers for unknown primary cancers are not uniformly specific or sensitive, a large series of marker studies should be avoided. Communication with the pathologist is essential to workup.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Occult Primary

Ettinger¹,

Agulnik²,

Cates³

et al. 2011

J Natl Compr Canc Netw

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“…Recent studies demonstrated familial clustering of CUP and the association of CUP with many other cancers, especially those originating from organs suspected to be responsible for many CUP diagnoses 1,8 . Accordingly, CUP often occurred in relatives of patients with lung, colorectal (CRC) liver, ovary and kidney cancers, among others 5,6,7 .…”

Section: Introductionmentioning

confidence: 99%

“…The disorder is slightly more common in men than in women, and predominantly affects adults (less than 1% of patients with diagnosed solid CUP are children) 3,4 . Most cases of CUP are carcinomas, which are divided into adenocarcinomas of well or moderate differentiation (60%), undifferentiated or poorly differentiated adenocarcinomas (30%), squamous-cell carcinomas (5%), and undifferentiated neoplasms (5%) 3,7,9 . CUP may occasionally present as mixed tumors, adenocarcinoma with neuroendocrine components, or sarcomatoid carcinoma 5,9 .…”

Section: Introductionmentioning

confidence: 99%

“…CUP represents a heterogeneous group of metastatic tumors for which no primary site can be detected following a through medical history, careful clinical examination and extensive diagnostic work-up 1,5,7 . Diagnostic approaches to identify the primary site include radiological assessment, modern imaging technology (computed tomography, digital mammography, positron emission tomography), detailed histopathological examination and tumoral markers workup with specific immunohistochemistry 1,2,5,7 . Upon detection of a metastasis of unknown origin, extensive diagnostic work-up is undertaken to optimize the treatment 2, .…”

Section: Introductionmentioning

confidence: 99%

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Metástases hepáticas de primário difícil de encontrar…

Mondragão¹,

Ramos²,

Costa³

et al. 2017

Gal. Clin.

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RESUMOO cancro de primário desconhecido é responsável por cerca de 3-5% de todas as neoplasias malignas e é, portanto, um dos 10 diagnósticos de cancro mais frequentes. A tecnologia de imagem moderna e o estudo anatomopatológico desenvolvido (imuno-histoquímica, microscopia eletrónica e diagnóstico molecular) resultaram na melhoria do diagnóstico; no entanto, os primários permanecem ocultos na maioria dos doentes, mesmo pós-autópsia. Os locais mais comuns de origem são os tumores do pulmão e pâncreas. O cancro de origem desconhecida é diagnosticado num estadio metastático, conferindo um prognóstico desfavorável. O fíga-do é um dos órgãos mais comumente envolvido na doença metastática, que surge com mais frequência de primários no cólon. A colonoscopia é o gold standard para avaliação da mucosa do cólon e reto. É apresentado um doente de 64 anos, sem história médica de relevo, que recorreu ao serviço de urgência por dor no flanco direito. A ecografia abdominal revelou metastização hepática difusa. A tomografia computadorizada referia suspeita de espessamento do cólon ascendente mas a endoscopia e colonoscopia (com uma boa visibilidade da válvula ileocecal) não tinham alterações. Palavras-chave: Colonoscopia; cancro colorretal; metástases hepáticas; cancro de primário desconhecido. ABSTRACTMetastatic Cancer of Unknown Primary Site (CUP) accounts for approximately 3-5% of all malignant neoplasms and is therefore one of the 10 most frequent cancer diagnoses. Modern imaging technology and extensive work-up with specific pathology investigations (immunohistochemistry, electron microscopy and molecular diagnosis) have resulted in some improvements in diagnosis; however, the primary site remains unknown in most patients, even on autopsy. The most prevalent sites of primary tumors origin are the lung and pancreas. CUP is diagnosed at a metastatic stage, conferring an unfavorable prognosis. The liver is one of the most common organs to be involved with metastatic disease, which arises most frequently from primary sites in the colon. A total colonoscopy is the gold standard for the evaluation of the colon. We present a 64-year--old man with no remarkable past medical history, which presented to the Emergency Service with right flank pain. The abdominal ultrasound revealed diffuse lesions suggestive of hepatic metastases. A computerized tomography (CT) scan showed thickening of ascending colon, but upper and lower endoscopies (with a good view of the ileocecal valve) and other diagnostic procedures were unremarkable.

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Overview of Patient Management and Future Directions in Unknown Primary Carcinoma

Cited by 24 publications

References 18 publications

Validation of a microRNA-based qRT-PCR test for accurate identification of tumor tissue origin

Validation of a microRNA-based qRT-PCR test for accurate identification of tumor tissue origin

Occult Primary

Metástases hepáticas de primário difícil de encontrar…

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