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

• Published in: PloS one Vol. 16; no. 4; p. e0249767
• Main Authors: Klingen, Tor A, Chen, Ying, Aas, Hans, Wik, Elisabeth, Akslen, Lars A
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 09.04.2021; Public Library of Science (PLoS)
• Subjects: Biology and Life Sciences; Biomarkers; Biomarkers, Tumor - metabolism; Breast cancer; Breast Neoplasms - metabolism; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Calcium-Binding Proteins - metabolism; Cancer; Cancer therapies; Clinical medicine; Editing; Elastic Tissue - metabolism; Electronic mail; Ethics; Extracellular Matrix Proteins - metabolism; Female; Fibers; Genetic aspects; Humans; Mammography; Medical prognosis; Medical screening; Medicine; Medicine and Health Sciences; Neoplasm Invasiveness; Pathology; Patient outcomes; Patients; Prognosis; Retrospective Studies; Statistical analysis; Surgery; Survival Rate; Thyroid; Thyroid gland; Tumors; Norway
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0249767

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.