Cancer of unknown primary (CUP) represents a common and important clinical problem. There is evidence that most CUPs are metastases of carcinomas whose primary site cannot be recognized. Driven by the hypothesis that the knowledge of primary cancer could improve patients prognosis, we investigated microRNA expression profiling as a tool for identifying the tissue-of-origin of metastases. We assessed microRNA expression from 101 formalin-fixed paraffin-embedded (FFPE) samples from primary cancers and metastases samples by using a microarray platform. Forty samples representing 10 different cancer types were used for defining a cancer-type-specific microRNA signature, which was used for predicting primary sites of metastatic cancers. A 47-miRNAs signature was identified and used to estimate tissue-of-origin probabilities for each sample. Overall, accuracy reached 100% for primary cancers and 78% for metastases in our cohort of samples. When the signature was applied to an independent published dataset of 170 samples, accuracy remained high: correct prediction was found within the the first two options in 86% of the metastasis cases (first prediction was correct in 68% of cases). This signature was also applied to predict 16 CUPs. In this group, first predictions exhibited probabilities higher than 90% in most of the cases. These results establish that FFPE samples can be used to reveal the tissue of origin of metastatic cancers by using microRNA expression profiling and suggest that the approach, if applied, could provide strong indications for CUPs, whose correct diagnosis is presently undefined.

MicroRNA profiling for the identification of cancers with unknown primary tissue-of-origin

FERRACIN, Manuela
Primo
;
PEDRIALI, Massimo
Secondo
;
VERONESE, Angelo;ZAGATTI, Barbara;GAFA', Roberta;MAGRI, Eros;LUNARDI, Maria;MUNERATO, Gardenia;QUERZOLI, Giulia;MAESTRI, Iva;ULAZZI, Linda;NENCI, Italo;CROCE, Carlo Maria;LANZA, Giovanni;QUERZOLI, Patrizia
Penultimo
;
NEGRINI, Massimo
Ultimo
2011

Abstract

Cancer of unknown primary (CUP) represents a common and important clinical problem. There is evidence that most CUPs are metastases of carcinomas whose primary site cannot be recognized. Driven by the hypothesis that the knowledge of primary cancer could improve patients prognosis, we investigated microRNA expression profiling as a tool for identifying the tissue-of-origin of metastases. We assessed microRNA expression from 101 formalin-fixed paraffin-embedded (FFPE) samples from primary cancers and metastases samples by using a microarray platform. Forty samples representing 10 different cancer types were used for defining a cancer-type-specific microRNA signature, which was used for predicting primary sites of metastatic cancers. A 47-miRNAs signature was identified and used to estimate tissue-of-origin probabilities for each sample. Overall, accuracy reached 100% for primary cancers and 78% for metastases in our cohort of samples. When the signature was applied to an independent published dataset of 170 samples, accuracy remained high: correct prediction was found within the the first two options in 86% of the metastasis cases (first prediction was correct in 68% of cases). This signature was also applied to predict 16 CUPs. In this group, first predictions exhibited probabilities higher than 90% in most of the cases. These results establish that FFPE samples can be used to reveal the tissue of origin of metastatic cancers by using microRNA expression profiling and suggest that the approach, if applied, could provide strong indications for CUPs, whose correct diagnosis is presently undefined.
2011
Ferracin, Manuela; Pedriali, Massimo; Veronese, Angelo; Zagatti, Barbara; Gafa', Roberta; Magri, Eros; Lunardi, Maria; Munerato, Gardenia; Querzoli, Giulia; Maestri, Iva; Ulazzi, Linda; Nenci, Italo; Croce, Carlo Maria; Lanza, Giovanni; Querzoli, Patrizia; Negrini, Massimo
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/1432915
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