Columnar cell lesions and pseudoangiomatous hyperplasia like stroma: Is there an epithelial-stromal interaction?

Department of Pathology at Magee Women's Hospital of University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
International journal of clinical and experimental pathology (Impact Factor: 1.89). 01/2009; 3(1):87-97.
Source: PubMed


The significance of association between cancer and its microenvironment has been increasingly recognized. It has been shown in animal models that interaction between neoplastic epithelial cells and adjacent stroma can modulate tumor behavior. Carcinoma associated stromal cells can transform normal epithelial cells into neoplastic cells. In breast, columnar cell lesions are non-obligate precursors of low grade ductal carcinoma in situ. Columnar cell lesions can be seen intimately associated with PASH-like-stroma, a lesion we termed as CCPLS. Our aim is to investigate epithelial-stromal interactions in CCPLS and compare them to PASH without columnar cell lesions in breast core needle biopsies. Normal terminal duct lobular unit (TDLU) epithelium was seen in association with columnar cell lesions as well as PASH. Eight (8) cases of each category were examined by a panel of immunostains: CD117 (C-kit), CD34, CD105, bFGF, AR, ER-beta, MIB-1. We observed a markedly decreased expression of c-kit in columnar cell lesions compared to TDLU-epithelium. CD105 showed a quantitative increase in activated vessels in CCPLS compared to PASH. A subset of CCPLS and PASH were androgen receptor positive. A strong nuclear positivity for ER-beta is observed in the epithelium and stroma of all CCPLS cases. We conclude that (1) activated blood vessels predominate in CCPLS; (2) A molecular alteration is signified by c-kit loss in columnar cell lesions; (3) ER-beta and androgen receptor positivity indicate CCPLS are hormonally responsive lesions. Our study suggests an intimate vascular and hormone dependent epithelial-stromal interaction exists in CCPLS lesions.

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    ABSTRACT: Columnar cell hyperplasia (CCH) is the earliest histologically identifiable breast lesion linked to cancer progression and is characterized by increased proliferation, decreased apoptosis and elevated oestrogen receptor α (ERα) expression. The mechanisms underlying the initiation of these lesions have not been clarified but might involve early and fundamental changes in cancer progression. MiRNAs are key regulators of several biological processes, acting by influencing the post-transcriptional regulation of numerous targets, thus making miRNAs potential candidates in cancer initiation. Here we have defined novel epithelial as well as stromal miRNA signatures from columnar cell hyperplasia lesions compared to normal terminal duct lobular units by using microdissection and miRNA microarrays. Let-7c were among the identified downregulated epithelial miRNAs and its functions were delineated in unique CCH derived cells and breast cancer cell line MCF-7 suggesting anti-proliferative traits potentially due to effects on Myb and ERα. MiR-132 was upregulated in the stroma surrounding CCH compared to stoma surrounding normal terminal duct lobular units (TDLUs), and overexpression of miR-132 in immortalized fibroblasts and in fibroblasts co-cultured with epithelial CCH cells caused substantial expression changes of genes involved in metabolism, DNA damage and cell motility. The miRNA signatures identified in CCH indicate early changes in the epithelial and stromal compartment of CCH and could represent early key alterations in breast cancer progression that potentially could be targeted in novel prevention or treatment schedules.
    PLoS ONE 08/2014; 9(8):e105099. DOI:10.1371/journal.pone.0105099 · 3.23 Impact Factor
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    ABSTRACT: INTRODUCTION Pseudoangiomatous stromal hyperplasia (PASH) is a benign breast lesion that can be mistaken for angiosarcoma or fibroadenoma. This rare condition generally tends to present as a palpable mass in premenopausal women which can be seen on mammogram and ultrasound alike. The pathological findings tend to be of a thickening of the stroma and anastomosing channels arranged concentrically around the lobules. METHOD A literature search was carried out using SCOPUS, keywords Pseudoangiomatous, Stromal, Hyperplasia, or “PASH”. Relevant articles were obtained in full. CONCLUSIONS PASH appears to have hormonal influences and can be mistaken for breast cancer clinically and radiologically. A greater understanding of the histological appearances of PASH is key to attaining the correct diagnosis. FNAC is not adequate for this purpose - core biopsy or excision are recommended. DISCUSSION PASH is a benign condition. It can present a diagnostic challenge as it may mimic breast cancer both clinically and radiologically. Whilst there has been no definite proof of an association with invasive breast cancer PASH may be found in neighbouring tissue of invasive or in situ disease. There are currently no guidelines regarding follow up or management of patients with PASH. This article aims to increase the awareness of this rare condition and review the literature pertaining to the topic.
    Journal of OncoPathology 09/2014; 2(3). DOI:10.13032/tjop.2052-5931.100100


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