Abstract P1-03-07: The "panta rhei" of breast cancer: Gene expression timeline analysis during progression of microinvasive breast cancer microenvironment
Authors: Lessi F , Scatena C , Aretini P , Menicagli M , Franceschi S , Ortenzi V , La Ferla M , De Gregorio V , Bevilacqua G , Naccarato GA , Mazzanti CM 
Published: May 2016

Background. Tumors develop by progression through a series of stages. It is now widely accepted that cancer is attributed to the accumulation of genetic alterations in cells. Every cells of the tumor microenvironment is constantly changing in the flow of the cancer progression. A number of genes have been identified as having functions in various stages of progression in promoting cancer progression in experimental models. However, the association between gene expression alterations and resulting phenotypic alterations with respect to the aggressiveness and migration potential of cancer cells is not fully understood. Therefore, elucidation of genotype–phenotype correlation will be required to further understand the complex process of progression and invasion. All tumors require at least some stroma to meet their needs of nutrition, waste removal, and structure. It has become clear in recent years that stroma is essential for tumor maintenance and growth and has potential as a therapeutic target. Here, we aimed to give a chronological order of gene expression changes given in the dynamical framework of microinvasive breast cancer microenvironment.

Materials and Methods. RNA-seq (Ion Proton technology) was performed on three microinvasive breast cancers, applying new modifications to the usual protocol. For each of them we microdissected 7 different portions of the tumor (around 200 cells), 4 related to the breast epithelium and 3 to the stroma. The regions were selected on the basis of their grade of progression. Breast epithelium was chronologically subdivided in normal breast epithelium (NBE), carcinoma in situ (CIS), emerging invasive fingers (EIF) and invasive breast cancer (IBC). For each of the breast epithelium subdivisions we collected the adjacent stroma (S) except for the in situ portion: S-NBE, S-EIF and S-IBC.

Results: Whole transcriptome analysis performed on each microdissected regions reveals a series of gene expression changes occurring during cancer progression in the breast epithelium along with the adjacent stroma. The dendogram analysis, based on the whole gene expression data of each patient revealed a perfect group organization of the various microdissected portions of stroma and mammary epithelium. Within the dendogram, the organization of Normal, In Situ, EIF and Invasive tissue respected perfectly the biological assumptions.

Conclusions: More thorough analyses are needed to give a clear view of the flow of molecular events starting from the normal breast epithelium to the microinvasive stage, as well as to give a better understanding of the stroma-epithelium molecular means of communication. The analysis of all the molecular changes occuring in the breast epithelium and in the stroma of microinvasive cancer could lead to the development of new therapeutic targets.

Citation Format: Lessi F, Scatena C, Aretini P, Menicagli M, Franceschi S, Ortenzi V, La Ferla M, De Gregorio V, Bevilacqua G, Naccarato GA, Mazzanti CM. The "panta rhei" of breast cancer: Gene expression timeline analysis during progression of microinvasive breast cancer microenvironment. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-03-07.