Invasive and drug resistant expression profile of different morphological structures of breast tumors

E. V. DENISOV, T. S. GERASHCHENKO, M. V. ZAVYALOVA, N. V. LITVIAKOV, M. M. TSYGANOV, E. V. KAIGORODOVA, E. M. SLONIMSKAYA, J. KZHYSHKOWSKA, N. V. CHERDYNTSEVA, V. M. PERELMUTER

Abstract:

In order to understand invasive/adhesive and drug resistant properties of intratumor morphological heterogeneity of breast cancer, we compared the expression of genes responsible for the cell adhesion and for the drug resistance between distinct morphological structures of breast tumors. Tubular (hollow-like), alveolar (morula-like), trabecular, solid structures/patterns, and discrete (small) groups of tumor cells were isolated from invasive carcinoma of no special type (n=3) and invasive micropapillary carcinoma (n=1) of the breast using laser microdissection. The gene expression of cadherins, catenins, integrins, ABC transporters, GSTP1, and drug targets was analyzed using qRT-PCR. Expression of catenin genes was identified in almost all structures. In contrast, the expression of cadherin and integrin genes significantly varied depending on the morphological variant. Cadherin expression declined in the row: solid – alveolar and trabecular structures – discrete groups of tumor cells. Expression of integrins declined in the row: solid and alveolar – trabecular structures – discrete groups of tumor cells. For drug resistance genes, trabecular structures more often demonstrated activity of genes coding for ABC transporters compared to other morphological variants. These results indicate that intratumoral morphological heterogeneity in breast cancer correlates with expression profile of adhesion and drug resistance genes reflecting different patterns of invasive growth and responsiveness to chemotherapy.