Defining invasion in breast cancer: the role of basement membrane

Abstract

Basement membrane (BM) is an amorphous, sheet-like structure separating the epithelium from the stroma. BM is characterised by a complex structure comprising collagenous and non-collagenous proteoglycans and glycoproteins. In the breast, the thickness, density and composition of the BM around the ductal lobular system vary during differing development stages. In pathological conditions, the BM provides a physical barrier that separates proliferating intraductal epithelial cells from the surrounding stroma, and its absence or breach in malignant lesions is a hallmark of invasion and metastases. Currently, diagnostic services often use special stains and immunohistochemistry (IHC) to identify the BM in order to distinguish in situ from invasive lesions. However, distinguishing BM on stained sections, and differentiating the native BM from the reactive capsule or BM-like material surrounding some invasive malignant breast tumours is challenging. Although diagnostic use of the BM is being replaced by myoepithelial cell IHC markers, BM is considered by many to be a useful marker to distinguish in situ from invasive lesions in ambiguous cases. In this review, the structure, function and biological and clinical significance of the BM are discussed in relation to the various breast lesions with emphasis on how to distinguish the native BM from alternative pathological tissue mimicking its histology.

The most likely but largely ignored triggering factor for breast (or all) cancer invasion

“…The EP is the origin of a majority of the human malignances 3 , 4 . The breast capsule is made of the myoepithelial cell layer (MECL, a single cell layer embracing the EP) and basement membrane (BM, a thin layer of fibers and smooth muscle cells attached to the MECL) 5 , 6 . The prostate and salivary tissues share similar capsule constitutes with the breast, whereas other cancers have only the BM constituting the capsule 7 , 8 .…”

Encapsulated papillary carcinoma of the breast: does it have a native basement membrane?

“…4 BM is a thin, pliable sheet-like material of extracellular matrix (ECM) that sits between normal or proliferative intraductal epithelial and MEC and the surrounding connective tissue. 5 In malignant tumours, preservation of BM denotes in situ disease, while its absence is a feature of invasive tumours. 5 Although some DCIS shows expansion of the BM, this is different from the reactive fibrous tissue capsule seen around some benign and malignant tumours in various tissue and organs including renal cell carcinomas, hepatocellular carcinomas and thyroid follicular carcinomas, and their benign counterparts.…”

“…5 In malignant tumours, preservation of BM denotes in situ disease, while its absence is a feature of invasive tumours. 5 Although some DCIS shows expansion of the BM, this is different from the reactive fibrous tissue capsule seen around some benign and malignant tumours in various tissue and organs including renal cell carcinomas, hepatocellular carcinomas and thyroid follicular carcinomas, and their benign counterparts. 6 Tumour encapsulation refers to the presence of a fibrous capsule surrounding the neoplasm and is often associated with indolent clinical behaviour.…”

“…1,9 The outer layer of the BM that faces the ECM is called the reticular lamina, or lamina fibro-reticularis, and is mainly formed of collagen III. 5 Previous studies have demonstrated that collagen III coexpressed with collagen I, resulting in regulation of fibrils dimensions that influence their mechanical stiffness and functional properties. 10,11 Collagen III has a key role in normal tension maintenance and modulating scar formation.…”

“…BM is a thin, pliable sheet‐like material of extracellular matrix (ECM) that sits between normal or proliferative intraductal epithelial and MEC and the surrounding connective tissue 5 . In malignant tumours, preservation of BM denotes in situ disease, while its absence is a feature of invasive tumours 5 …”