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

Tor A Klingen,Elisabeth Wik,Ying Chen,Hans Aas,Lars A Akslen

doi:10.1371/journal.pone.0249767

Tor A Klingen, Elisabeth Wik + Show 3 more

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https://doi.org/10.1371/journal.pone.0249767

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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.

Highlights

Stromal elastosis, defined as dense aggregates of elastic fibers, is found in some neoplastic tissues and especially in malignant tumours of the breast [1], lung [2] and thyroid gland [3]
We previously reported that breast cancer stromal elastosis is associated with a favorable prognosis, low tumour cell proliferation by Ki67 expression, and mammography detection compared
The aim of this study was to establish whether perivascular fibulin-2 expression is associated with patient prognosis in breast cancer, and to see whether this expression pattern is related to vascular invasion, stromal elastosis, molecular subtypes, and tumour detection mode

Summary

Introduction

Stromal elastosis, defined as dense aggregates of elastic fibers, is found in some neoplastic tissues and especially in malignant tumours of the breast [1], lung [2] and thyroid gland [3]. We previously reported that breast cancer stromal elastosis is associated with a favorable prognosis, low tumour cell proliferation by Ki67 expression, and mammography detection compared.

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