Genetic up-regulation and overexpression of PLEKHA7 differentiates invasive lobular carcinomas from invasive ductal carcinomas.

Molecular differentiation between invasive lobular carcinomas (ILCs) and invasive ductal carcinomas (IDCs) of the breast has not been well defined. We investigated gene expression differences between ILCs and IDCs and their correlation with variations in invasiveness and tumor growth. Total RNA was isolated from 30 frozen tumor samples: 10 from ILCs and 20 from IDCs. Gene expression was investigated using the Affymetrix GeneChip Human Gene 1.0 ST Array (Affymetrix, Santa Clara, CA). Data and validation were performed by reverse transcriptase polymerase chain reaction and immunohistochemistry. Gene expression differences between ILCs and IDCs were found in 140 genes. Overall, ILCs showed up-regulation of genes related with cell migration, lipid and fatty acid metabolism, and some transcription factors and showed down-regulation of cell adhesion, actin cytoskeleton, cell proliferation, and energetic metabolism of the tumor cells. Our reverse transcriptase polymerase chain reaction results showed that PLEKHA and TMSB10 expression discriminated ILCs from luminal A IDCs, whereas PLEKHA7, TMSB10, PRDX4, and SERPINB5 discriminated ILCs from luminal B IDCs. At the protein level, Plekha7 was overexpressed in ILCs but not in normal tissue or low-grade IDCs. Moreover, Plekha7 overexpression had an inverse relation with E-cadherin expression. The gene expression profile in ILCs and IDCs differs in several signaling pathways. Our findings suggest that overexpression of PLEKHA7 is common in ILCs and could be a molecular marker to differentiate ILCs from IDCs.