Prognostic value of proliferation assay in the luminal, HER2-positive, and triple-negative biologic classes of breast cancer

Aleskandarany, Mohammed A.; Green, Andrew; Benhasouna, Ahmed; Barros, F.; Neal, Keith; Reis‐Filho, Jorge S.; Ellis, Ian O.; Rakha, Emad A.

doi:10.1186/bcr3084

Cited by 110 publications

(91 citation statements)

References 36 publications

(53 reference statements)

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“…Her2+ breast cancers were identified as ER − , PR − and strongly Her2+, while basal-like breast cancers were defined by the absence of ER, PR and Her2 expression. [7][8][9][10] Luminal A, luminal B and basal-like breast cancers showed significantly higher levels of CCL2 and Fsp1 expression in whole tissues, compared with normal breast tissues (Figure 4a). There were no significant differences in epithelial CCL2 and Fsp1 expression among the different tissue types (Figure 4b).…”

Section: Stromal Ccl2 Associates With Decreased Relapse-free Survivalmentioning

confidence: 99%

“…Histologically, these subtypes are classified by the status of estrogen receptor (ER), progesterone receptor (PR), Her2 and cell proliferative index. [7][8][9][10] Conventional prognostic indicators such as grade and stage do not accurately predict patient prognosis for all of the different molecular subtypes, 11,12 indicating the need to identify prognostic factors unique to each subtype.…”

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confidence: 99%

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Elevated expression of chemokine C-C ligand 2 in stroma is associated with recurrent basal-like breast cancers

Yao

Staggs

et al. 2016

Modern Pathology

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Despite advances in treatment, up to 30% of breast cancer patients experience disease recurrence accompanied by more aggressive disease and poorer prognosis. Treatment of breast cancer is complicated by the presence of multiple breast cancer subtypes, including: luminal, Her2 overexpressing, and aggressive basal-like breast cancers. Identifying new biomarkers specific to breast cancer subtypes could enhance the prediction of patient prognosis and contribute to improved treatment strategies. The microenvironment influences breast cancer progression through expression of growth factors, angiogenic factors and other soluble proteins. In particular, chemokine C-C ligand 2 (CCL2) regulates macrophage recruitment to primary tumors and signals to cancer cells to promote breast tumor progression. Here we employed a software-based approach to evaluate the prognostic significance of CCL2 protein expression in breast cancer subtypes in relation to its expression in the epithelium or stroma or in relation to fibroblast-specific protein 1 (Fsp1), a mesenchymal marker. Immunohistochemistry analysis of tissue microarrays revealed that CCL2 significantly correlated with Fsp1 expression in the stroma and tumor epithelium of invasive ductal carcinoma. In the overall cohort of invasive ductal carcinomas (n = 427), CCL2 and Fsp1 expression in whole tissues, stroma and epithelium were inversely associated with cancer stage and tumor size. When factoring in molecular subtype, stromal CCL2 was observed to be most highly expressed in basal-like breast cancers. By Cox regression modeling, stromal CCL2, but not epithelial CCL2, expression was significantly associated with decreased recurrence-free survival. Furthermore, stromal CCL2 (HR = 7.51 P = 0.007) was associated with a greater hazard than cancer stage (HR = 2.45, P = 0.048) in multivariate analysis. These studies indicate that stromal CCL2 is associated with decreased recurrence-free survival in patients with basal-like breast cancer, with important implications on the use of stromal markers for predicting patient prognosis.

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Section: Stromal Ccl2 Associates With Decreased Relapse-free Survivalmentioning

confidence: 99%

mentioning

confidence: 99%

Elevated expression of chemokine C-C ligand 2 in stroma is associated with recurrent basal-like breast cancers

Yao

Staggs

et al. 2016

Modern Pathology

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“…Supplementary table 1 displays sources, dilution, cut-off point and pre-treatment conditions used of the antibodies of DNA damage sensing and repair markers used in this study. The staining conditions as well as data dichotomy of other markers in this study were defined as previously described [18][19][20][21][22]. This study was approved by Nottingham Research Ethics Committee 2.…”

Section: Study Cohortmentioning

confidence: 99%

“…In this series, HER2 was assessed using IHC (DAKO) and dual-colour chromogenic in-situ hybridisation (CISH) as previously published [20]. Ki67 labelling index (Ki67LI) was assessed on full-face tumour tissue sections and was assessed as the percentage of Ki67 positive cells among a total number of 1000 malignant cells at high power magnification (x400) [20]. Supplementary table 1 displays sources, dilution, cut-off point and pre-treatment conditions used of the antibodies of DNA damage sensing and repair markers used in this study.…”

Section: Study Cohortmentioning

confidence: 99%

Clinical and biological significance of RAD51 expression in breast cancer: a key DNA damage response protein

Alshareeda

Negm

Aleskandarany

et al. 2016

Breast Cancer Res Treat

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Purpose: Impaired DNA-damage response (DDR) may play a fundamental role in the pathogenesis of breast cancer (BC). RAD51 is key player in DNA double strand break repair.In this study, we aimed to assess the biological and clinical significance of RAD51 expression with relevance to different molecular classes of BC and patients' outcome. Methods:The expression of RAD51 was assessed immunohistochemically in a wellcharacterised annotated series (n=1184) of early-stage invasive BC with long-term follow-up.A subset of cases of BC from patients with known BRCA1 germline mutations was included as a control group. The results were correlated with clinicopathological and molecular parameters and patient outcome. RAD51 protein expression level was also assayed in a panel of cell lines using reverse phase protein array (RPPA). Conclusions: lack of RAD51 nuclear expression is associated with poor prognostic parameters and shorter survival in invasive BC patients. The significant associations between RAD51 subcellular localisation and clinicopathological features, molecular subtype and patients' outcome suggest that the trafficking of DDR proteins between the nucleus and cytoplasm might play a role in the development and progression of BC.3

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“…These results suggested that 30% is a suitable cutoff in the HER2-positive (non-luminal) subgroup and the cutoff for the Ki67 score should be changed for breast cancer subgroups. We also noted the recent research by Aleskandarany et al; 23 they assessed the prognostic value of a proliferation assay using Ki67 IHC compared with mitotic count scores in the luminal, HER2-positive, and triple-negative biological classes of breast cancer. They found that neither mitotic count nor Ki67 score was associated with outcome in the HER2-positive or the triple-negative classes.…”

Section: Discussionmentioning

confidence: 99%

Quantum dot-based immunofluorescent imaging of Ki67 and identification of prognostic value in HER2-positive (non-luminal) breast cancer

Sun¹,

Chen²,

Jiang³

et al. 2014

IJN

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Background The immunohistochemical assessment of Ki67 antigen (Ki67) is the most widely practiced measurement of breast cancer cell proliferation; however, it has some disadvantages and thus the prognostic value of Ki67 in breast cancer remains controversial. Our previous studies confirmed the advantages of quantum dots-based nanotechnology for quantitative analysis of biomarkers compared with conventional immunohistochemistry (IHC). This study was designed to assess Ki67 by quantum dot-immunohistochemistry (QD-IHC) and investigate the prognostic value of the Ki67 score in human epidermal growth factor receptor 2 (HER2)-positive (non-luminal) breast cancer. Methods Ki67 expression in 108 HER2-positive (non-luminal) breast cancer specimens was detected by IHC and QD-IHC. Two observers assessed the Ki67 score independently and comparisons between the two methods were made. The prognostic value of the Ki67 score for five-year disease-free survival was estimated. Results The same antigen localization, high correlation of staining rates ( r =0.993), and high agreement of measurements (κ=0.874) of Ki67 expression (cutoff: 30%) in breast cancer were found by QD-IHC and conventional IHC. The QD-IHC had a better interobserver agreement for the Ki67 score than conventional IHC ( t =−7.280, P <0.01). High Ki67 expression (cutoff: 30%) was associated with shorter disease-free survival (log-rank test; IHC, P =0.026; QD-IHC, P =0.001), especially in the lymph node-negative subgroups (log-rank test; IHC, P =0.017; QD-IHC, P =0.002). Conclusion QD-IHC imaging of Ki67 was an easier and more accurate method for detecting and assessing Ki67. The Ki67 score was an independent prognosticator in the HER2-positive (non-luminal) breast cancer patients.

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Prognostic value of proliferation assay in the luminal, HER2-positive, and triple-negative biologic classes of breast cancer

Cited by 110 publications

References 36 publications

Elevated expression of chemokine C-C ligand 2 in stroma is associated with recurrent basal-like breast cancers

Elevated expression of chemokine C-C ligand 2 in stroma is associated with recurrent basal-like breast cancers

Clinical and biological significance of RAD51 expression in breast cancer: a key DNA damage response protein

Quantum dot-based immunofluorescent imaging of Ki67 and identification of prognostic value in HER2-positive (non-luminal) breast cancer

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