Cancer of unknown primary origin: a decade of experience in a community-based hospital

Pimiento, José M.; Teso, Desarom; Malkan, Alpin D.; Dudrick, Stanley J.; Palesty, J. Alexander

doi:10.1016/j.amjsurg.2007.08.039

Cited by 37 publications

(32 citation statements)

References 19 publications

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“…However, after complete assessment, including history, physical examination, imaging, and pathological evaluation of tumor samples, a substantial fraction of cases remain unidentified. [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.…”

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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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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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“…Furthermore, results of the multivariate analysis revealed that younger age, larger tumor size, lymphovascular space invasion and hilar lymph node involvement were correlated with an increased risk of developing brain metastases. Pimiento et al reported that the pathologic diagnoses of 91 CUP patients included adenocarcinoma (42.8%), undifferentiated carcinoma (34.5%), squamous cell carcinoma (9.8%), neuroendocrine cancer (6.5%), sarcoma (3.2%), and non-specific malignant neoplasm (3.2%) (1). Nonetheless, squamous cell and neuroendocrine CUP are associated with a significantly more favorable early prognosis than other malignancies.…”

Section: Discussionmentioning

confidence: 99%

“…Cancer of unknown primary origin (CUP) is an aggressive disease with a poor prognosis (1). The most frequently detected primary carcinomas are those that are concealed in the lungs or pancreas (2).…”

Section: Introductionmentioning

confidence: 99%

A case of primary lung cancer lesion demonstrated by F-18 FDG positron emission tomography/computed tomography (PET/CT) one year after the detection of metastatic brain tumor

Ozeki¹,

Abe²,

Kita³

et al. 2011

Oncology Letters

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Abstract. Cancer of unknown primary origin (CUP) is an aggressive disease with a poor prognosis. Metastatic brain tumors occur in approximately 15% of all cancer patients. F-18 2'-deoxy-2fluoro-D-glucose (FDG) positron emission tomography (PET) combined with computed tomography (PET/CT) contributes to the evaluation of cancer staging, although the benefits of PET/CT for detection of CUP origins has yet to be determined. In this study, we present a 37-year-old man with a brain tumor detected by magnetic resonance imaging. Surgical biopsy indicated a metastatic undifferentiated carcinoma, while clinical examination and a CT scan did not detect any abnormalities, with the exception of brain metastases. PET/CT did not reveal abnormal FDG uptake. PET/CT revealed abnormal intense FDG uptake in a small nodular lesion in the right lung 1 year following the detection of brain metastasis, and no other abnormal FDG uptake was observed elsewhere in the body. Right upper lobectomy and dissection of mediastinal lymph nodes were performed. The pathological diagnosis was poorly differentiated adenocarcinoma, which was similar to the brain metastatic lesion, and there was no lymph node metastasis. This case revealed an extremely rare lung cancer with primary lesions demonstrated by PET/CT 1 year after the detection of brain metastasis. This case reveals that F-18 FDG PET/CT imaging of CUP origin is capable of positively impacting on the identification of small primary tumor foci.

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“…Of significant importance is a study performed by Rosenfeld et al (2008), which needed only 48 miRNA markers to identify 22 tissue origins with an accuracy of 90%. This work holds promise for the 3-5% of patients from all new cancer cases diagnosed with metastatic cancer of unknown primary origin (Pimiento et al, 2007). Enabling oncologists to identify the tissue of origin will markedly improve treatment decision and prognosis.…”

Section: Introductionmentioning

confidence: 99%

MicroRNAs as potential cancer therapeutics

2008

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Cancer of unknown primary origin: a decade of experience in a community-based hospital

Cited by 37 publications

References 19 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

A case of primary lung cancer lesion demonstrated by F-18 FDG positron emission tomography/computed tomography (PET/CT) one year after the detection of metastatic brain tumor

MicroRNAs as potential cancer therapeutics

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