Is intratumoral morphological heterogeneity of breast cancer accompanied by specific changes of miRNA expression?

Abstract

Aim The aim was to find out how morphological heterogeneity within each tumor reflects the miRNA expression profile and whether there is a link between a certain type of morphological differentiation and type of miRNA expression. Methods We used microdissection techniques for the isolation of cells from paraffin sections of breast carcinomas with a heterogeneous morphological picture, the isolation of RNA and miRNA microarray analysis. Results In the cases analyzed, the greatest differences between benign structures, areas with incipient invasion, typical invasive carcinoma and structures of another histological type of cancer (other morphological types which formed part of the structure included adenoid cystic carcinoma, papillary carcinoma and/or metaplastic apocrine carcinoma) were observed for 16 miRNAs (compared to benign structures): miR-10b, miR-19b, miR-21, miR-32, miR-139, miR-181d, miR-182, miR-378C, miR-378f, miR-486, miR-497, miR-502, miR-628, miR-1263, miR-3201 and miR-4529. Conclusions We have identified four miRNAs that have not been described as markers associated with the development of a tumor. These are miR-32, miR-1263, miR-3201 and miR-4529. None of the 16 miRNAs (with the exception of miR-21 and miR-497) have been in former literature associated with differentiation status and certainly not with the morphology within individual tumors. The novelty of our access lies in analysis of the expression profile of morphologically distinct parts of the same tumor which is more convenient than association studies based on comparison of large groups of tumors. The results could contribute to the discovery of new principles governing morphogenesis and differentiation in tumors and could be of practical importance for determining the prognosis of the disease.