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Clin Cancer Res. 2011 Jun 15;17(12):4063-70. doi: 10.1158/1078-0432.CCR-10-2599. Epub 2011 Apr 29.

Prospective gene signature study using microRNA to identify the tissue of origin in patients with carcinoma of unknown primary.

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1
Departments of Gastrointestinal Medical Oncology and Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Abstract

PURPOSE:

Accurate identification of tissue of origin (ToO) for patients with carcinoma of unknown primary (CUP) may help customize therapy to the putative primary and thereby improve the clinical outcome. We prospectively studied the performance of a microRNA-based assay to identify the ToO in CUP patients.

EXPERIMENTAL DESIGN:

Formalin-fixed paraffin-embedded (FFPE) metastatic tissue from 104 patients was reviewed and 87 of these contained sufficient tumor for testing. The assay quantitates 48 microRNAs and assigns one of 25 tumor diagnoses by using a biologically motivated binary decision tree and a K-nearest neighbors (KNN). The assay predictions were compared with clinicopathologic features and, where suitable, to therapeutic response.

RESULTS:

Seventy-four of the 87 cases were processed successfully. The assay result was consistent or compatible with the clinicopathologic features in 84% of cases processed successfully (71% of all samples attempted). In 65 patients, pathology and immunohistochemistry (IHC) suggested a diagnosis or (more often) a differential diagnosis. Out of those, the assay was consistent or compatible with the clinicopathologic presentation in 55 (85%) cases. Of the 9 patients with noncontributory IHC, the assay provided a ToO prediction that was compatible with the clinical presentation in 7 cases.

CONCLUSIONS:

In this prospective study, the microRNA diagnosis was compatible with the clinicopathologic picture in the majority of cases. Comparative effectiveness research trials evaluating the added benefit of molecular profiling in appropriate CUP subsets are warranted. MicroRNA profiling may be particularly helpful in patients in whom the IHC profile of the metastasis is nondiagnostic or leaves a large differential diagnosis.

PMID:
21531815
DOI:
10.1158/1078-0432.CCR-10-2599
[Indexed for MEDLINE]
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