Fibulin-2 expression associates with vascular invasion and patient survival in breast cancer

PLoS One. 2021 Apr 9;16(4):e0249767. doi: 10.1371/journal.pone.0249767. eCollection 2021.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Calcium-Binding Proteins / metabolism*
  • Elastic Tissue / metabolism*
  • Extracellular Matrix Proteins / metabolism*
  • Female
  • Humans
  • Neoplasm Invasiveness
  • Prognosis
  • Retrospective Studies
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • Calcium-Binding Proteins
  • Extracellular Matrix Proteins
  • fibulin 2

Grants and funding

T.A.K. was supported by the Vestfold Hospital Research Fund for this study. This work was also partly supported by the Research Council of Norway through its Centres of Excellence funding scheme, project number 223250 (L.A.A.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. There was no additional external funding received for this study.