Poorly Differentiated Neoplasms of Unknown Primary Site: Diagnostic Usefulness of a Molecular Cancer Classifier Assay

Greco, F. Anthony; Lennington, Wayne J.; Spigel, David R.; Hainsworth, John D.

doi:10.1007/s40291-015-0133-8

Cited by 39 publications

(20 citation statements)

References 14 publications

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“…Rossi et al (2015) observed higher frequencies, in descending order, of non-determined neoplasms for carcinomas, sarcomas, melanomas, and mastocytomas but no cases of lymphoma. This information is corroborated by recent studies in human patients (GRECO et al, 2015), in which lymphoma was the less diagnosed neoplasm of unknown origin.…”

Section: Case Reportsupporting

confidence: 77%

Metastatic T-cell lymphoma of unknown primary origin in a dog (Canis lupus familiaris)

Rodrigues

Borges

Lima

et al. 2017

AVB

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Section: Case Reportsupporting

confidence: 77%

Metastatic T-cell lymphoma of unknown primary origin in a dog (Canis lupus familiaris)

Rodrigues

Borges

Lima

et al. 2017

AVB

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“…Based on this assumption, molecular methods using gene expression profiling, gene microarrays, microRNA, and DNA methylation analysis are increasingly employed as classifier assays to predict the TOO. Conceptually, the TOO classifiers are trained on a database of TOO-specific molecular signatures established by analyzing primaries of known origin and can predict the TOO of known primaries with accuracies of 76-96% (29)(30)(31)(32)(33)(34)(35). As already pointed out elsewhere, an important limitation of this approach is the number of different tumor types used in training the TOO classifier (36).…”

Section: Chasing the Tissue Of Origin (Too) In Cupmentioning

confidence: 99%

“Metastatic Cancer of Unknown Primary” or “Primary Metastatic Cancer”?

et al. 2020

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Cancer of unknown primary (CUP) is an umbrella term used to classify a heterogeneous group of metastatic cancers based on the absence of an identifiable primary tumor. Clinically, CUPs are characterized by a set of distinct features comprising early metastatic dissemination in an atypical pattern, an aggressive clinical course, poor response to empiric chemotherapy and, consequently, a short life expectancy. Two opposing strategies to change the dismal prognosis for the better are pursued. On the one hand, following the traditional tissue-gnostic approach, more and more sophisticated tissue-of-origin (TOO) classifier assays are employed to push identification of the putative primary to its limits with the clear intent of allowing tumor-site specific treatment. However, robust evidence supporting its routine clinical use is still lacking, notably with two recent randomized clinical trials failing to show a patient benefit of TOO-prediction based site-specific treatment over empiric chemotherapy in CUP. On the other hand, with regards to a tissue-agnostic strategy, precision medicine approaches targeting actionable genomic alterations have already transformed the treatment for many known tumor types. Yet, an unmet need remains for well-designed clinical trials to scrutinize its potential role in CUP beyond anecdotal case reports. In the absence of practice changing results, we believe that the emphasis on finding the presumed unknown primary tumor at all costs, implicit in the term CUP, has biased recent research in the field. Focusing on the distinct clinical features shared by all CUPs, we advocate adopting the term primary metastatic cancer (PMC) to denominate a distinct cancer entity instead. In our view, PMC should be considered the archetype of metastatic disease and as such, despite accounting for a mere 2-3% of malignancies, unraveling the mechanisms at play goes beyond improving the prognosis of patients with PMC and promises to greatly enhance our understanding of the metastatic process and carcinogenesis across all cancer types.

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“…Gene expression profiling is an effective approach in identifying the primary tumor site in CUP [ 78 ]. The expression levels of messenger RNA (mRNA) or micro-RNA (miRNA) can be assessed using reverse-transcription polymerase chain reaction (RT-PCR) or oligonucleotide microarray technology [ 79 , 80 ].…”

Section: Histopathological Diagnosismentioning

confidence: 99%

“…The expression levels of messenger RNA (mRNA) or micro-RNA (miRNA) can be assessed using reverse-transcription polymerase chain reaction (RT-PCR) or oligonucleotide microarray technology [ 79 , 80 ]. Currently, two commercially available assays capable of identifying the primary tumor in approximately 80% of cases are available [ 78 , 81 ]. The clinical utility of these assays is supported by the results of a phase II trial, suggesting a survival benefit in patients treated with site-specific therapy based on a gene expression profile [ 81 ]; moreover, the results of a phase III trial addressing this issue (GEFCAPI 04) are incoming [ 82 ].…”

Section: Histopathological Diagnosismentioning

confidence: 99%

The pathogenesis, diagnosis, and management of metastatic tumors to the ovary: a comprehensive review

Kubeček

Laco

Špaček

et al. 2017

Clin Exp Metastasis

127

109

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Secondary tumors of the ovary account for 10–25% of all ovarian malignancies. The most common tumors that give rise to ovarian metastases include breast, colorectal, endometrial, stomach, and appendix cancer. The correct diagnosis of secondary ovarian tumors may be challenging as they are not infrequently misdiagnosed as primary ovarian cancer, particularly in the case of mucinous adenocarcinomas. The distinction from the latter is essential, as it requires different treatment. Immunohistochemistry plays an important role in distinguishing primary ovarian tumors from extra-ovarian metastases and, furthermore, may suggest the primary tumor site. Despite extensive study, some cases remain equivocal even after assessing a broad spectrum of antigens. Therefore, gene expression profiling represents an approach able to further discriminate equivocal findings, and one that has been proven effective in determining the origin of cancer of unknown primary site. The available data concerning secondary ovarian tumors is rather limited owing to the relative heterogeneity of this group and the practical absence of any prospective trials. However, several intriguing questions are encountered in daily practice, including rational diagnostic workup, the role of cytoreductive surgery, and consequent adjuvant chemotherapy. This review seeks to address these issues comprehensively and summarize current knowledge on the epidemiology, pathogenesis, and management of secondary ovarian tumors, including further discussion on the different pathways of metastatisation, metastatic organotropism, and their possible molecular mechanisms.

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Poorly Differentiated Neoplasms of Unknown Primary Site: Diagnostic Usefulness of a Molecular Cancer Classifier Assay

Cited by 39 publications

References 14 publications

Metastatic T-cell lymphoma of unknown primary origin in a dog (Canis lupus familiaris)

Metastatic T-cell lymphoma of unknown primary origin in a dog (Canis lupus familiaris)

“Metastatic Cancer of Unknown Primary” or “Primary Metastatic Cancer”?

The pathogenesis, diagnosis, and management of metastatic tumors to the ovary: a comprehensive review

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