A substantial number of ductal carcinoma in situ (DCIS) detected by mammography never progress to invasive ductal carcinoma (IDC) and current approaches fail to identify low-risk patients not at need of adjuvant therapies. We aimed to identify the key miRNAs protecting DCIS from malignant evolution, that may constitute markers for non-invasive lesions. We studied 100 archived DCIS samples, including pure DCIS, DCIS with adjacent IDC and pure DCIS from patients with subsequent IDC in contralateral breast or no recurrence. A DCIS derived cell line was used for molecular and cellular studies. A genome wide study revealed that pure DCIS has higher miR-126 and miR-218 expression than DCIS with adjacent IDC lesions or than IDC. The down-regulation of miR-126 and miR-218 promoted invasiveness in vitro and, in patients with pure DCIS, was associated with later onset of IDC. Survival studies of independent cohorts indicated that both miRNAs play a protective role in IDC. The clinical findings are in agreement with the miRNAs' roles in cell adhesion, differentiation and proliferation.

Levels of miR-126 and miR-218 are elevated in ductal carcinoma in situ (DCIS) and inhibit malignant potential of DCIS derived cells

Scatena, Cristian;Mazzanti, Chiara Maria;Naccarato, Giuseppe;
2018

Abstract

A substantial number of ductal carcinoma in situ (DCIS) detected by mammography never progress to invasive ductal carcinoma (IDC) and current approaches fail to identify low-risk patients not at need of adjuvant therapies. We aimed to identify the key miRNAs protecting DCIS from malignant evolution, that may constitute markers for non-invasive lesions. We studied 100 archived DCIS samples, including pure DCIS, DCIS with adjacent IDC and pure DCIS from patients with subsequent IDC in contralateral breast or no recurrence. A DCIS derived cell line was used for molecular and cellular studies. A genome wide study revealed that pure DCIS has higher miR-126 and miR-218 expression than DCIS with adjacent IDC lesions or than IDC. The down-regulation of miR-126 and miR-218 promoted invasiveness in vitro and, in patients with pure DCIS, was associated with later onset of IDC. Survival studies of independent cohorts indicated that both miRNAs play a protective role in IDC. The clinical findings are in agreement with the miRNAs' roles in cell adhesion, differentiation and proliferation.
Volinia, Stefano; Bertagnolo, Valeria; Grassilli, Silvia; Brugnoli, Federica; Manfrini, Marco; Galasso, Marco; Scatena, Cristian; Mazzanti, Chiara Maria; Lessi, Francesca; Naccarato, Giuseppe; Caligo, Adelaide; Bianchini, Enzo; Piubello, Quirino; Orvieto, Enrico; Rugge, Massimo; Natali, Cristina; Reale, Domenico; Vecchione, Andrea; Warner, Sarah; Croce, Carlo Maria; Capitani, Silvano
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11568/933602
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