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Expression of Cancer/Testis genes in ductal carcinoma in situ and benign lesions of the breast.

ABSTRACT: Cancer/testis (CT) genes represent a unique class of genes, which are expressed by germ cells, normally silenced in somatic cells, but activated in various cancers. CT proteins can elicit spontaneous immune responses in cancer patients and this feature makes them attractive targets for immunotherapy-based approaches. We have previously reported that CTs are relatively commonly expressed in estrogen receptor (ER) negative, high risk carcinomas. In this study, we examined the expression of selected CT genes in ductal carcinoma in situ (DCIS), lobular carcinoma in situ (LCIS) and benign proliferative lesions of the breast. ER negative DCIS were found to be associated with significant CT gene expression together with HER2 positivity and a marked stromal immune response.

SUBMITTER: Caballero OL

PROVIDER: S-EPMC4295763 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Expression of Cancer/Testis genes in ductal carcinoma in situ and benign lesions of the breast.

Caballero Otavia L OL Shousha Sami S Zhao Qi Q Simpson Andrew J G AJG Coombes R Charles RC Neville A Munro AM

Oncoscience 20131212 1

Cancer/testis (CT) genes represent a unique class of genes, which are expressed by germ cells, normally silenced in somatic cells, but activated in various cancers. CT proteins can elicit spontaneous immune responses in cancer patients and this feature makes them attractive targets for immunotherapy-based approaches. We have previously reported that CTs are relatively commonly expressed in estrogen receptor (ER) negative, high risk carcinomas. In this study, we examined the expression of selecte ...[more]

PMID: 25593980

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Project description:Background Most ductal carcinoma in situ (DCIS) lesions are first detected on screening mammograms as calcifications. However, false-positive biopsy rates for calcifications range from 30% to 87%. Improved methods to differentiate benign from malignant calcifications are thus needed. Purpose To quantify the growth rates of DCIS and benign breast disease that manifest as mammographic calcifications. Materials and Methods All calcifications (n = 2359) for which a stereotactic biopsy was performed from 2008 through 2015 at Duke University Medical Center were retrospectively identified. Mammograms from all cases of DCIS (n = 404) were reviewed for calcifications that were visible on mammograms taken at least 6 months before biopsy. Women with at least one prior mammogram with visible calcifications were age- and race-matched 1:2 to women with a benign breast biopsy and calcifications visible on prior mammograms. The long axis of the calcifications was measured on all mammograms. Multivariable adjusted linear mixed-effects models estimated the association of calcification growth rates with patholo findings. Hierarchical clustering accounted for matching benign and DCIS groups. Results A total of 74 DCIS calcifications and 148 benign calcifications were included for final analysis. The median patient age was 62 years (interquartile range, 51-71 years). No significant difference in breast density (P > .05) or number of available mammograms (P > .05) was detected between groups. Calcifications associated with DCIS were larger than those associated with benign breast disease at biopsy (median, 10 mm vs 6 mm, respectively; P < .001). After adjustment, the relative annual increase in the long-axis length of DCIS calcifications was greater than that of benign breast calcifications (96% [95% confidence interval: 72%, 224%] vs 68% [95% confidence interval: 56%, 80%] per year, respectively; P < .001). Conclusion Ductal carcinoma in situ calcifications are more extensive at diagnosis and grow faster in extent than those associated with benign breast disease. The rate of calcification change may help to discriminate benign from malignant calcifications. © RSNA, 2019 Online supplemental material is available for this article.

Project description:IntroductionBreast atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS) are precursor stages of invasive ductal carcinoma (IDC). This study aimed to investigate the pathogenesis of breast cancer by dynamically analyzing expression changes of hub genes from normal mammary epithelium (NME) to simple ductal hyperplasia (SH), ADH, DCIS, and finally to IDC.MethodsLaser-capture microdissection (LCM) data for NME, SH, ADH, DCIS, and IDC cells were obtained. Weighted gene co-expression network analysis (WGCNA) was performed to dynamically analyze the gene modules and hub genes associated with the pathogenesis of breast cancer. Tissue microarray, immunohistochemical, and western blot analyses were performed to determine the protein expression trends of hub genes.ResultsTwo modules showed a trend of increasing expression during the development of breast disease from NME to DCIS, whereas a third module displayed a completely different trend. Interestingly, the three modules displayed inverse trends from DCIS to IDC compared with from NME to DCIS; that is, previously upregulated modules were subsequently downregulated and vice versa. We further analyzed the module that was most closely associated with DCIS (p=7e-07). Kyoto Gene and Genomic Gene Encyclopedia enrichment analysis revealed that the genes in this module were closely related to the cell cycle (p= 4.3e-12). WGCNA revealed eight hub genes in the module, namely, CDK1, NUSAP1, CEP55, TOP2A, MELK, PBK, RRM2, and MAD2L1. Subsequent analysis of these hub genes revealed that their expression levels were lower in IDC tissues than in DCIS tissues, consistent with the expression trend of the module. The protein expression levels of five of the hub genes gradually increased from NME to DCIS and then decreased in IDC. Survival analysis predicted poor survival among breast cancer patients if these hub genes were not downregulated from DCIS to IDC.ConclusionsFive hub genes, RRM2, TOP2A, PBK, MELK, and NUSAP1, which are associated with breast cancer pathogenesis, are gradually upregulated from NME to DCIS and then downregulated in IDC. If these hub genes are not downregulated from DCIS to IDC, patient survival is compromised. However, the underlying mechanisms warrant further elucidation in future studies.

Dataset Information

Expression of Cancer/Testis genes in ductal carcinoma in situ and benign lesions of the breast.

Publications

Expression of Cancer/Testis genes in ductal carcinoma in situ and benign lesions of the breast.

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