Mucinous Carcinoma of the Breast, One or Two Diseases? MiRNAs and Molecular Profiling of Invasive and In Situ Mucinous Carcinoma
Luis Vicioso, Ang Li, Alfredo Matilla, Karlena Lara, Maria J Merino. NCI, Bethesda, MD; Hospital Clinico, Malaga, Spain
Background: Mucinous carcinoma (MC) is a rare subtype of ductal carcinoma of breast generally associated with good prognosis. Recently, two types of tumor have been recognized, type A or paucicellular, and type B hypercellular with neuroendocrine differentiation. MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression by targeting mRNAs. They have been implicated in regulation of cellular growth and differentiation and have been found to dysregulate cell proliferation in human tumors, including breast cancer. We evaluated the phenotypic and molecular characteristics of mucinous tumors and performed miRNA profiling searching for similarities/differences between the two types and the DCIS associated with type B.
Design: We studied 30 cases of MC. IHC for ER, PR, Her2, and MiB1 was performed in all cases. Twelve cases representing high and low cellularity tumors, and associated DCIS were microdissected and RNA was extracted. MiRNAs expression was profiled with miRNA array (nCounter Human v2 miRNA assay, Nanospring) and the data was analyzed using nSolver and Partek. The relative miRNA levels were indicated as median fold changes and a cut off of 2 folds was used.
Results: Patients age range from 36-86 years.Five patients (B type) had nodal metastasis (1-4 + nodes). All cases were ER+, 26 were PR+ and 2 were Her2+ but only one had FISH amplification. We identified 14 (9 up / 5 down) differentially expressed miRNAs associated with type B mucinous tumors (including upregulated miR-21-5p and miR-125b-5p and downregulated miR-494 and miR-720). 26 miRNAs (11 up and 15 down) were found to be aberrantly expressed in the high cellular tumors, relative to their associated DCIS (including upregulated miR-188-5p and miR-363-3p and downregulated miR-125a-5p and miR-1283). There were 9 commonly deregulated miRNAs (6 up and 3 down) in carcinomas with high cellularity when compared to low cellularity tumors and DCIS (including upregulated miR-144-3p, miR-149-5p, miR-320e, miR-338-3p, miR-631, and miR-2682-5p and downregulated miR-200c-3p, miR-1260a, and miR-4454).
Conclusions: Our study demonstrates that invasive type B mucinous carcinoma has a different miRNA expression pattern from those with low cellularity and from the associated DCIS. This microRNA signature most likely reflects unique molecular changes for each group of lesions, and it can not only prove to be useful in diagnosis and prognosis, it can also have great impact in the development of new molecular targets and therapy.
Tuesday, March 5, 2013 9:15 AM
Proffered Papers: Section B, Tuesday Morning