14 research outputs found
Vessel size as a marker of survival in estrogen receptor positive breast cancer
Background Angiogenesis is crucial for tumor growth and is one of the hallmarks of cancer. In this study, we analyzed microvessel density, vessel median size, and perivascular a-SMA expression as prognostic biomarkers in breast cancer.Methods A set of dual IHC staining was performed where alpha-SMA antibodies were used together with antibodies against the endothelial cell marker CD34. Digital images of stainings were analyzed to extract quantitative data on vessel density, vessel size and perivascular alpha-SMA status.Results The analyses in the discovery cohort (n = 108) revealed a statistically significant relationship between large vessel size and shorter disease specific survival (p = 0.007, log-rank-test; p = 0.01, HR 3.1; 95% CI: 1.3–7.4, Cox-regression analyses). Subset analyses indicated that the survival association of vessel size was enriched in ER + breast cancer. To consolidate these findings, additional analyses were performed on the validation cohort (n = 267) where a significant poor prognosis association of large vessel size was also detected in ER + breast cancer (p = 0.016, log-rank-test; p = 0.02; HR 2.3, 95% CI: 1.1–4.7, Cox-regression analyses).Conclusions Alpha-SMA/CD34 dual IHC staining revealed breast cancer heterogeneity regarding vessel size, vessel density and perivascular a-SMA status. Large vessel size was linked to shorter survival in ER + breast cancer.</p
Vessel size as a marker of survival in estrogen receptor positive breast cancer
Angiogenesis is crucial for tumor growth and is one of the hallmarks of cancer. In this study, we analyzed microvessel density, vessel median size, and perivascular a-SMA expression as prognostic biomarkers in breast cancer. Dual IHC staining was performed where alpha-SMA antibodies were used together with antibodies against the endothelial cell marker CD34. Digital images of stainings were analyzed to extract quantitative data on vessel density, vessel size and perivascular alpha-SMA status. The analyses in the discovery cohort (n = 108) revealed a statistically significant relationship between large vessel size and shorter disease specific survival (p = 0.007, log-rank-test; p = 0.01, HR 3.1; 95% CI: 1.3–7.4, Cox-regression analyses). Subset analyses indicated that the survival association of vessel size was strengthened in ER + breast cancer. To consolidate these findings, additional analyses were performed on a validation cohort (n = 267) where an association between large vessel size and reduced survival was also detected in ER + breast cancer (p = 0.016, log-rank-test; p = 0.02; HR 2.3, 95% CI: 1.1–4.7, Cox-regression analyses). Alpha-SMA/CD34 dual IHC staining revealed breast cancer heterogeneity regarding vessel size, vessel density and perivascular a-SMA status. Large vessel size was linked to shorter survival in ER + breast cancer.</p
Extra-nodal extension is a significant prognostic factor in lymph node positive breast cancer
QSOX1 expression is associated with aggressive tumor features and reduced survival in breast carcinomas
Comparison between Ki67 labeling index determined using image analysis software with virtual slide system and that determined visually in breast cancer
Expression of Nestin associates with BRCA1 mutations, a basal-like phenotype and aggressive breast cancer
We here examined whether Nestin, by protein and mRNA levels, could be a predictor of BRCA1 related breast cancer, a basal-like phenotype, and aggressive tumours. Immunohistochemical staining of Nestin was done in independent breast cancer hospital cohorts (Series I-V, total 1257 cases). Also, TCGA proteomic data (n = 103), mRNA microarray data from TCGA (n = 520), METABRIC (n = 1992), and 6 open access breast cancer datasets (n = 1908) were analysed. Patients with Nestin protein expression in tumour cells more often had BRCA1 germline mutations (OR 8.7, p < 0.0005, Series III), especially among younger patients (<40 years at diagnosis) (OR 16.5, p = 0.003). Nestin protein positivity, observed in 9–28% of our hospital cases (Series I-IV), was independently associated with reduced breast cancer specific survival (HR = 2.0, p = 0.035) and was consistently related to basal-like differentiation (by Cytokeratin 5, OR 8.7–13.8, p < 0.0005; P-cadherin OR 7.0–8.9, p < 0.0005; EGFR staining, OR 3.7–8.2, p ≤ 0.05). Nestin mRNA correlated significantly with Nestin protein expression (ρ = 0.6, p < 0.0005), and high levels were seen in the basal-like intrinsic subtype. Gene expression signalling pathways linked to high Nestin were explored, and revealed associations with stem-like tumour features. In summary, Nestin was strongly associated with germline BRCA1 related breast cancer, a basal-like phenotype, reduced survival, and stemness characteristics
