Fibulin-2 expression associates with vascular invasion and patient survival in breast cancer
Open Access
- 9 April 2021
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 16 (4), e0249767
- https://doi.org/10.1371/journal.pone.0249767
Abstract
Stromal elastosis is related to good prognosis in breast cancer and fibulin-2 helps to stabilize elastic fibers in basement membranes. Here, we examined the level of perivascular fibulin-2 expression in relation to elastosis content, vascular invasion, molecular subtypes, tumour detection mode, and patient prognosis in breast cancer. We performed a population based retrospective study of invasive breast cancers from the Norwegian Breast Screening Program (Vestfold County, 2004–2009) including 200 screen-detected and 82 interval cancers. Perivascular fibulin-2 staining was semi-quantitatively graded based on immunohistochemistry (1–3) and dichotomized as high expression (grade 2–3) and low expression (grade 1). Elastosis content was graded on a 4-tiered scale and dichotomized as high (score 3) and low (score 0–2) expression, whereas lymphatic (LVI) and blood vessel invasion (BVI) were recorded as absent or present by immunohistochemistry. High perivascular fibulin-2 expression was strongly related to stromal elastosis (p<0.001), and inversely associated with BVI and LVI (p<0.001 for both). High fibulin-2 was associated with luminal breast cancer subgroups (p<0.001) and inversely with interval cancers compared with screen-detected tumours (p<0.001). By univariate analysis, low perivascular fibulin-2 was associated with reduced recurrence-free survival (p = 0.002) and disease specific survival (p = 0.019). Low perivascular fibulin-2 expression was strongly related to vascular invasion, low stromal elastosis, non-luminal breast cancer subtypes, interval presentation, and adverse prognosis.Funding Information
- The Research Council of Norway (223250)
- Vestfold Hospital Research Fund
This publication has 31 references indexed in Scilit:
- Tumour cell invasion into blood vessels is significantly related to breast cancer subtypes and decreased survivalJournal of Clinical Pathology, 2016
- Human breast cancer invasion and aggression correlates with ECM stiffening and immune cell infiltrationIntegrative Biology, 2015
- Breast cancer stromal elastosis is associated with mammography screening detection, low Ki67 expression and favourable prognosis in a population-based studyDiagnostic Pathology, 2014
- Fibulin-2 Is a Driver of Malignant Progression in Lung AdenocarcinomaPLOS ONE, 2013
- Expression of thyroid transcription factor-1 is associated with a basal-like phenotype in breast carcinomasDiagnostic Pathology, 2013
- Role of Fibulin-5 in Metastatic Organ ColonizationMolecular Cancer Research, 2011
- Fibulin-5 initiates epithelial-mesenchymal transition (EMT) and enhances EMT induced by TGF- in mammary epithelial cells via a MMP-dependent mechanismCarcinogenesis: Integrative Cancer Research, 2008
- Placental Cadherin and the Basal Epithelial Phenotype of BRCA1-Related Breast CancerClinical Cancer Research, 2005
- The combination of angiogenesis and blood vessel invasion as a prognostic indicator in primary breast cancerBritish Journal of Cancer, 2003
- pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long‐term follow‐upHistopathology, 1991