scholarly journals Breast cancer risk factors in relation to estrogen receptor, progesterone receptor, insulin-like growth factor-1 receptor, and Ki67 expression in normal breast tissue

2017 ◽  
Vol 3 (1) ◽  
Author(s):  
Hannah Oh ◽  
A. Heather Eliassen ◽  
Andrew H. Beck ◽  
Bernard Rosner ◽  
Stuart J. Schnitt ◽  
...  
2017 ◽  
Author(s):  
Kevin C. Johnson ◽  
E. Andres Houseman ◽  
Jessica E. King ◽  
Brock C. Christensen

AbstractBackgroundThe underlying biological mechanisms through which epidemiologically defined breast cancer risk factors contribute to disease risk remain poorly understood. Identification of the molecular changes associated with cancer risk factors in normal tissues may aid in determining the earliest events of carcinogenesis and informing cancer prevention strategies.ResultsHere we investigated the impact cancer risk factors have on the normal breast epigenome by analyzing DNA methylation genome-wide (Infinium 450K array) in cancer-free women from the Susan G. Komen Tissue Bank (n = 100). We tested the relation of established breast cancer risk factors: age, body mass index, parity, and family history of disease with DNA methylation adjusting for potential variation in cell-type proportions. We identified 787 CpG sites that demonstrated significant associations (Q-value < 0.01) with subject age. Notably, DNA methylation was not strongly associated with the other evaluated breast cancer risk factors. Age-related DNA methylation changes are primarily increases in methylation enriched at breast epithelial cell enhancer regions (P = 7.1E-20), and binding sites of chromatin remodelers (MYC and CTCF). We validated the age-related associations in two independent populations of normal breast tissue (n = 18) and normal-adjacent to tumor tissue (n = 97). The genomic regions classified as age-related were more likely to be regions altered in cancer in both pre-invasive (n = 40, P=3.0E-03) and invasive breast tumors (n = 731, P=1.1E-13).ConclusionsDNA methylation changes with age occur at regulatory regions, and are further exacerbated in cancer suggesting that age influences breast cancer risk in part through its contribution to epigenetic dysregulation in normal breast tissue.


2017 ◽  
Vol 21 (8) ◽  
pp. 464-470 ◽  
Author(s):  
Abdolreza Daraei ◽  
Pantea Izadi ◽  
Ghasemali Khorasani ◽  
Nahid Nafissi ◽  
Mohammad Mehdi Naghizadeh ◽  
...  

2018 ◽  
Author(s):  
Ashutosh Kumar ◽  
Khursheed Raza ◽  
Tapas C. Nag ◽  
Anurag Srivastava ◽  
Ritu Sehgal

AbstractBackgroundThe pathophysiology of the breast phyllodes tumours is uncertain. Currently, wide surgical removal is the only available treatment option. The histopathological diagnosis of phyllodes tumours is often confused with that of fibroadenomas due to a striking histological resemblance; hence a distinctive biomarker for this tumour type is warranted.Material & MethodsFresh human breast tissue was obtained from surgically excised breast phyllodes and fibroadenoma tumours (test, 2 cases each), breast cancer (positive control, 2 cases) and normal breast tissue (negative control, 1 case). Immunohistochemistry was performed for the detection of nerve growth factor (NGF) on frozen sections of the test and control tissues fixed in 4% paraformaldehyde, using the indirect streptavidin-biotin-peroxidase complex method. Sandwich ELISA on tissue homogenates of the same test and control cases was also performed to validate the immunohistochemical findings.ResultsA marked difference in NGF expression was detected in phyllodes tumours compared to fibroadenomas. The maximum NGF expression was observed in phyllodes tissue followed by cancer tissue, and the least expression in fibroadenomas (3-5 times less than in phyllodes; comparable with normal breast tissue).ConclusionNGF is known for its growth inducing potential in breast cancer, but its secretion by a benign breast tumour is not known in literature. This study reports abundant NGF secretion by breast phyllodes, raising the possibility of its potential role in tumour pathogenesis and progression that can be exploited therapeutically in future. We also propose that NGF may be used as a distinct biomarker of phyllodes tumours, for differentiating them from fibroadenomas during histopathology.


2016 ◽  
Vol 2 (1) ◽  
Author(s):  
Hannah Oh ◽  
A Heather Eliassen ◽  
Molin Wang ◽  
Stephanie A Smith-Warner ◽  
Andrew H Beck ◽  
...  

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