Versican but not decorin accumulation is related to malignancy in mammographically detected high density and malignant-appearing microcalcifications in non-palpable breast carcinomas

Abstract

BackgroundMammographic density (MD) and malignant-appearing microcalcifications (MAMCs) represent the earliest mammographic findings of non-palpable breast carcinomas. Matrix proteoglycans versican and decorin are frequently over-expressed in various malignancies and are differently involved in the progression of cancer. In the present study, we have evaluated the expression of versican and decorin in non-palpable breast carcinomas and their association with high risk mammographic findings and tumor characteristics.MethodsThree hundred and ten patients with non-palpable suspicious breast lesions, detected during screening mammography, were studied. Histological examination was carried out and the expression of decorin, versican, estrogen receptor α (ERα), progesterone receptor (PR) and c-erbB2 (HER-2/neu) was assessed by immunohistochemistry.ResultsHistological examination showed 83 out of 310 (26.8%) carcinomas of various subtypes. Immunohistochemistry was carried out in 62/83 carcinomas. Decorin was accumulated in breast tissues with MD and MAMCs independently of the presence of malignancy. In contrast, versican was significantly increased only in carcinomas with MAMCs (median ± SE: 42.0 ± 9.1) and MD (22.5 ± 10.1) as compared to normal breast tissue with MAMCs (14.0 ± 5.8), MD (11.0 ± 4.4) and normal breast tissue without mammographic findings (10.0 ± 2.0). Elevated levels of versican were correlated with higher tumor grade and invasiveness in carcinomas with MD and MAMCs, whereas increased amounts of decorin were associated with in situ carcinomas in MAMCs. Stromal deposition of both proteoglycans was related to higher expression of ERα and PR in tumor cells only in MAMCs.ConclusionsThe specific accumulation of versican in breast tissue with high MD and MAMCs only in the presence of malignant transformation and its association with the aggressiveness of the tumor suggests its possible use as molecular marker in non-palpable breast carcinomas.

Insights into the key roles of proteoglycans in breast cancer biology and translational medicine

“…DSPGs expression was described to be increased in breast cancer fibroadenoma compared to healthy tissue [11]. A common finding is that matrix secreted CS/DSPGs such as decorin and versican are deposited in tumor stroma [12, 13] and are related to aggressive phenotype in breast cancer [14–16]. Relapse in women with node-negative breast cancer is related to the level of versican deposited in peritumoral stroma [14, 17].…”

“…It is accumulated in the preclinical phase of breast cancer in non-palpable breast carcinomas and is associated with risk factors such as increased mammographic density and malignant appearing microcalcifications [16]. Versican is increased in fibroadenoma [11] and the elevated levels of stromal versican are associated with increased risk and rate of relapse in women with node-negative breast cancer [14, 17].…”

Insidious Changes in Stromal Matrix Fuel Cancer Progression

“…Of note, immunohistochemical examination showed that syndecan-1, which was redistributed from the epithelium to the stroma, was over 10-fold higher in aggressive breast tissue compared to normal tissue [134]. Similarly, fibroblast-secreted versican, promotes tumor growth, migration, and metastasis in breast, ovarian, and prostate cancer [135–139], and is a product of paracrine TGF-β1 signaling in the latter. Stromal versican is associated with relapse and poorer outcome in cancer patients [140–142].…”

Functionalization of Iron Oxide Magnetic Nanoparticles with the Multivalent Pseudopeptide N6l for Breast Tumor Targeting

“…According to our previous data [25,27], we can assume that this targeting occurs in part through interaction between N6L and cellsurface nucleolin, which is overexpressed by tumor cells. However, several studies have shown that sulfated GAGs are overexpressed by tumor cells [31,32]. Analysis of the quantification of GAG have been evaluated from extract of tissue using carbazole assay and CS disacharide content.…”