Primary Breast Carcinoma: Association of Mammographic Calcifications with Osteopontin Expression

Xiao, Wang; Lan, Chao; Ma, Guansheng; Chen, Liansheng; Jin, Guangchao; Mao, Hua; Liu, Huiping; Ouyang, Aimei; Zhang, Xiulan

doi:10.1148/radiol.2541090675

Cited by 14 publications

(10 citation statements)

References 42 publications

(38 reference statements)

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“…Howland and coworkers reported that HER2 positivity is recognized to be associated with a higher incidence of LN metastases [23]. Several factors, including a higher ER-positivity rate, the prevalence of c-myc expression [24], as well as the elevated expression of osteopontin [25] and the ryanodine receptor 3 gene [26], were believed to contribute to the microcalcifications. Several factors, including HER2 positivity [23], the number of a CK19 mRNA copies [27], an elevated expression of osteopontin [25], T size and LVI [27], tumor grade [28], and clinical stage [28] were believed to contribute to lymph node metastases.…”

Section: Discussionmentioning

confidence: 99%

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BI-RADS 3-5 microcalcifications: prediction of lymph node metastasis of breast cancer

et al. 2017

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PurposeTo determine whether the clinicopathological parameters and Breast Imaging Reporting and Data System (BI-RADS) 3–5 microcalcifications differed between lymph node positive (LN (+)) and lymph node negative (LN (−)) invasive ductal carcinoma (IDC).ResultsFor microcalcification-associated breast cancers, seven selected features (age, tumor size, Ki-67 status, lymphovascular invasion, calcification range, calcification diameter and calcification density) were significantly associated with LN status (all P < 0.05). Multivariate logistic regression analysis found that three risk factors (age: older vs. younger OR: 0.973 P = 0.006, tumor size: larger vs. smaller OR: 1.671, P < 0.001 and calcification density: calcifications > 20/cm2 vs. calcifications ≤ 20/cm2 OR: 1.698, P < 0.001) were significant independent predictors. This model had an area under the receiver operating characteristic curve (AUC) of 0.701. The nodal staging (N0 and N1 χ2 = 5.701, P = 0.017; N0 and N2 χ2 = 6.614, P = 0.013) was significantly positively associated with calcification density. The luminal B subtype had the highest risk of LN metastasis. Multivariate analysis demonstrated that calcification > 2 cm in range (OR: 2.209) and larger tumor size (OR: 1.882) were independently predictive of LN metastasis in the luminal B subtype (AUC = 0.667).Materials and MethodsMammographic images of 419 female breast cancer patients were included. Associations between the risk factors and LN status were evaluated using a Chi-square test, ANOVA and binary logistic regression analysis.ConclusionsThis study found that age, tumor size and calcifications density can be conveniently used to facilitate the preoperative prediction of LN metastasis. The luminal B subtype has the highest risk of LN metastasis among the microcalcification-associated breast cancers.

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Section: Discussionmentioning

confidence: 99%

“…HER2-positive status (IHC 3+ or Fish+ and IHC 0/1+ or Fish-) was defined by the 2013 American Society of Clinical Oncology/College of American Pathology guidelines in our study [25, 35]. …”

Section: Methodsmentioning

confidence: 99%

BI-RADS 3-5 microcalcifications: prediction of lymph node metastasis of breast cancer

et al. 2017

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“…High levels of OPN have been detected in calcifications of both benign and malignant breast tissues [82]. Calcifications are more frequent in tumours overexpressing OPN than in OPN – tumours [83]. Although the significance of the presence of OPN in these calcifications is uncertain, in terms of whether OPN promotes or inhibits their formation, it may mean that some OPN‐expressing tumours are more readily detectable at early stages on the basis of associated abnormal or irregular mammographic calcifications.…”

Section: Effect Of Opn On the Tumour Microenvironmentmentioning

confidence: 99%

Role of the metastasis‐promoting protein osteopontin in the tumour microenvironment

Anborgh

Mutrie

Tuck³

et al. 2010

J Cellular Molecular Medi

163

114

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Osteopontin (OPN) is a secreted protein present in bodily fluids and tissues. It is subject to multiple post-translational modifications, including phosphorylation, glycosylation, proteolytic cleavage and crosslinking by transglutamination. Binding of OPN to integrin and CD44 receptors regulates signalling cascades that affect processes such as adhesion, migration, invasion, chemotaxis and cell survival. A variety of cells and tissues express OPN, including bone, vasculature, kidney, inflammatory cells and numerous secretory epithelia. Normal physiological roles include regulation of immune functions, vascular remodelling, wound repair and developmental processes. OPN also is expressed in many cancers, and elevated levels in patients’ tumour tissue and blood are associated with poor prognosis. Tumour growth is regulated by interactions between tumour cells and their tissue microenvironment. Within a tumour mass, OPN can be expressed by both tumour cells and cellular components of the tumour microenvironment, and both tumour and normal cells may have receptors able to bind to OPN. OPN can also be found as a component of the extracellular matrix. The functional roles of OPN in a tumour are thus complex, with OPN secreted by both tumour cells and cells in the tumour microenvironment, both of which can in turn respond to OPN. Much remains to be learned about the cross-talk between normal and tumour cells within a tumour, and the role of multiple forms of OPN in these interactions. Understanding OPN-mediated interactions within a tumour will be important for the development of therapeutic strategies to target OPN.

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“…In addition, the detection and characterization of calcifications are important in preoperative evaluations of lesion extent and surveillance after treatment in breast cancer patients 3 , 4 . There are well-established diagnostic criteria based on morphology and distribution of the calcifications at radiologic examination 5 , 6 . Evidence suggests that calcifications affect the prognosis of breast cancer, such that breast cancers with calcifications are predicted to be more aggressive and have worse prognosis than those without calcifications 7 – 13 .…”

Section: Introductionmentioning

confidence: 99%

Gene expression profiling of calcifications in breast cancer

Shin

Lee

Kim

et al. 2017

Sci Rep

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We investigated the gene expression profiles of calcifications in breast cancer. Gene expression analysis of surgical specimen was performed using Affymetrix GeneChip® Human Gene 2.0 ST arrays in 168 breast cancer patients. The mammographic calcifications were reviewed by three radiologists and classified into three groups according to malignancy probability: breast cancers without suspicious calcifications; breast cancers with low-to-intermediate suspicious calcifications; and breast cancers with highly suspicious calcifications. To identify differentially expressed genes (DEGs) between these three groups, a one-way analysis of variance was performed with post hoc comparisons with Tukey’s honest significant difference test. To explore the biological significance of DEGs, we used DAVID for gene ontology analysis and BioLattice for clustering analysis. A total of 2551 genes showed differential expression among the three groups. ERBB2 genes are up-regulated in breast cancers with highly suspicious calcifications (fold change 2.474, p < 0.001). Gene ontology analysis revealed that the immune, defense and inflammatory responses were decreased in breast cancers with highly suspicious calcifications compared to breast cancers without suspicious calcifications (p from 10−23 to 10−8). The clustering analysis also demonstrated that the immune system is associated with mammographic calcifications (p < 0.001). Our study showed calcifications in breast cancers are associated with high levels of mRNA expression of ERBB2 and decreased immune system activity.

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Primary Breast Carcinoma: Association of Mammographic Calcifications with Osteopontin Expression

Abstract: OPN could play a role in the formation of calcifications that often are associated with breast cancer.

Cited by 14 publications

References 42 publications

BI-RADS 3-5 microcalcifications: prediction of lymph node metastasis of breast cancer

BI-RADS 3-5 microcalcifications: prediction of lymph node metastasis of breast cancer

Role of the metastasis‐promoting protein osteopontin in the tumour microenvironment

Gene expression profiling of calcifications in breast cancer

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