Abstract
Abstract Purpose: To investigate relationships between microcalcifications and gene expression pattern using microarray analysis in breast cancer. Materials and methods: The institutional review board approved this retrospective study and waived the informed consent. Clinicopathologic finding, mammographic features, and gene expression data were evaluated in 133 women (mean age, 50.1 years; range, 21-79 years) with stage I-III breast cancer. Women with microcalcifications (n=33) and without microcalcifications (n=100) were compared. Immunohistochemical analysis of estrogen receptor, progesterone receptor, HER-2, and Ki-67 expression was performed. Differentially expressed genes (DEGs) using Affymetrix GeneChip® Human Gene 2.0 ST arrays (53,427 probes) were identified in tissue with microcalcifications versus without microcalcifications. In addition, genes included in the prediction analysis of PAM50, MammaPrint® and OncotypeDX® were also compared between two groups (microcalcifications versus no calcification). To further investigate the functions and underlying biology of DEGs, we performed enrichment analysis using the Gene Ontology database and pathway anlyais using the Kyoto Encyclopedia of Genes and Genomes database and Ingenuity Pathway Analysis. Results: Among clinicopathologic varibales, HER2 positivity (p<0.001) and presence of comedo necrosis (p=0.024) are significantly higher in the calcification group. About 128 genes had differential expression (> 1.5 fold difference, adjusted p value<0.05). Among known gene signatures, GRB7 (fold change=2.26, p=0.006) and ERBB2 (fold change=2.13, p=0.001) which are known as associated with recurrence, cell invasion and poor survival were highly expressed. In contrast, ZNF385B which is associated with p53-mediated apoptosis and good prognosis was underexpressed (fold change=0.39, p=0.001) in calcification group. Significant gene ontology terms included response to wounding, coagulation, wound healing, and response to hypoxia. Network and canonical pathway analysis indicated that increased cellular movement, cellular growth and proliferation, cellular develoment, coagulation and atherosclerosis signaling in breast cancer with microcalcifications, suggesting biological aggressiveness. Conclusion: Gene expression patterns are different according to microcalcifications status in breast cancer. Breast cancers with mammographic microcalcifications are associated with metabolic aggressiveness and poor prognosis. Citation Format: Shin SU, Kim W, Song SE, Chu A, Han W, Moon WK. Microcalcifications as imaging biomarker in breast cancer: High-throughput radiogenomic analysis using microarrya data. [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 P4-01-06.
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