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Sci Rep. 2018 May 8;8(1):7205. doi: 10.1038/s41598-018-25357-0.

Invasive lobular and ductal breast carcinoma differ in immune response, protein translation efficiency and metabolism.

Author information

1
Womens Cancer Research Center, UPMC Hillman Cancer Center, Magee Womens Research Institute, Pittsburgh, PA, 15213, USA.
2
School of Medicine, Tsinghua University, Beijing, 100084, China.
3
Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
4
Department of Pathology, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
5
Department of Pharmacology & Chemical Biology, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
6
Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213. Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA, 15232, USA.
7
Department of Computational & Systems Biology, Pittsburgh, PA, 15213, USA.
8
Womens Cancer Research Center, UPMC Hillman Cancer Center, Magee Womens Research Institute, Pittsburgh, PA, 15213, USA. oesterreichs@upmc.edu.
9
Department of Pharmacology & Chemical Biology, University of Pittsburgh, Pittsburgh, PA, 15213, USA. oesterreichs@upmc.edu.

Abstract

Invasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer following invasive ductal carcinoma (IDC). ILC differs from IDC in a number of histological and clinical features, such as single strand growth, difficulty in detection, and frequent late recurrences. To understand the molecular pathways involved in the clinical characteristics of ILC, we compared the gene expression profiles of luminal A ILC and luminal A IDC using data from TCGA and utilized samples from METABRIC as a validation data set. Top pathways that were significantly enriched in ILC were related to immune response. ILC exhibited a higher activity of almost all types of immune cells based on cell type-specific signatures compared to IDC. Conversely, pathways that were less enriched in ILC were related to protein translation and metabolism, which we functionally validated in cell lines. The higher immune activity uncovered in our study highlights the currently unexplored potential of a response to immunotherapy in a subset of patients with ILC. Furthermore, the lower rates of protein translation and metabolism - known features of tumor dormancy - may play a role in the late recurrences of ILC and lower detection rate in mammography and PET scanning.

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