Invasion in breast lesions: the role of the epithelial-stroma barrier (original) (raw)
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Breast disease, 2015
Ductal carcinoma in situ is the last step preceding invasive ductal carcinoma in breast carcinogenesis. We investigated the role of myoepithelial cells and epithelium characteristics as predictors of the risk of stromal invasion. We selected 236 cases with initial diagnosis of DCIS followed by surgical ressection distributed in groups 1 (without invasion) and 2 (with invasive carcinoma). The risk of stromal invasion after a DCIS diagnosis in biopsy was associated to triple-negative profile and loss of CD10 expression by myoepithelial cells, and inversely associated with CK5/6 expression by neoplastic cells and high expression of Smooth Muscle Myosin Heavy Chain (SMMHC) by myoepithelial cells. A combination of characteristics of epithelial and myoepithelial cells in DCIS in biopsy specimens is related to the risk of stromal invasion.
Myoepithelial cells and basal lamina in poorly differentiated in situ duct carcinoma of the breast
Virchows Archiv, 1999
A retrospective study was made of 38 selected brest tumours with a poorly differentiated in situ duct component. These were classified on haematoxylin and eosin (H&E) as ductal carcinoma in situ (DCIS; 10 cases), DCIS with invasion (17 cases) and DCIS with features suggestive of for stromal invasion (11 cases). The last were these lesions composed of neoplastic ducts with irregular outlines and a myoepithelial layer that was not clearly evident or large neoplastic ducts growing close together or surrounded by inflammatory desmoplastic stroma. Cases of DCIS involving areas of sclerosing adenosis were included in this category. Consecutive sections obtained from each case were studied with a panel of antibodies against myoepithelial cells (alpha smooth muscle actin and calponin) and basal lamina (BL) components (laminin and type IV collagen). It was found that in situ lesions showed well-formed basal lamina and/or an evident myoepithelial layer. These features were lacking in the invasive areas. Nine of the 11 cases with suggestive features of stromal invasion were reclassified as invasive duct carcinoma (5 cases)and DCIS (4 cases), according to the absence or presence of a continuous myoepithelial layer and/or basal lamina. In 2 such cases immunohistochemistry yielded equivocal results and the label "suggestive of invasion" was therefore pertinent. Immunohistochemistry facilitates the diagnosis of breast DCIS; myoepithelial and basal lamina markers are useful in differentiating microinvasive from in situ ductal carcinomas of the breast.
Virchows Archiv A Pathological Anatomy and Histopathology, 1988
Distributions of actin and type IV collagen were investigated immunohistochemically as markers for myoepithelial cells and basement membranes. Carnoy's and Methacarn-fixed, paraffin-embedded tissues from 103 human breast lesions from 103 patients were examined; 65 with carcinomas, 27 with mastopathies, 9 with fibroadenomas and 2 with phyllodes tumours. Fifty-five samples of the normal mammary gland tissue adjacent to tumours were also included for comparison. In normal breast and benign breast diseases, type IV collagen was identified around the mammary glandular cells and actin-positive cells were demonstrated to attach to basement membranes. In noninvasive carcinomas, type IV collagen was found as a continuous lining around a cell nest, while actin-positive cells were usually absent in ductal but quite numerous in lobular carcinomas. In invasive carcinomas, type IV collagen was fragmented or absent and actin-positive cells were very uncommon around the fragmentary basement membranes. These results suggest that the different distributions of myoepithelial cells and basement membrane material is useful in the differential diagnosis of surgical pathology of the breast.
Archives of Iranian Medicine, 2013
Background: This study seeks to determine the relationships between manifestation of myo broblasts in the stroma tissue of hyperplastic pre-invasive breast lesions to invasive cancer by investigating clinicopathological data of patients, their effect on steroid receptor expression and HER2, and angiogenesis according to CD34 antigen expression. Methods: Handred cases of invasive ductal carcinoma were immunohistochemically investigated for the presence of smooth muscle actin (SMA), ER/PR, HER2, anti-CD34 antibody and microvessel count (MVC). Patients were scored in four different zones of invasive areas: invasive cancer, DCIS, brocystic disease ± ductal intraepithelial neoplasia (FCD ± DIN), and normal tissue. Results: There was a signi cant difference in stromal myo broblasts between all areas except for the stroma of DCIS and FCD ± DIN (P < 0.001). We observed positive signi cant correlations between stromal myo broblasts, HER2 expression, and the numbers of involved lymph nodes in invasive cancer, DCIS, and FCD ± DIN (P < 0.001). More myo broblasts were present in grade III cases, with the least frequent observed among grade I cases in the stroma of those with invasive disease, DCIS, and FCD ± DIN (P < 0.001). MVC was inversely related to stromal myo broblasts in invasive cancer (P < 0.001) and DCIS (P < 0.001), whereas there was a positive correlation in the stroma of FCD ± DIN (P = 0.002) and normal areas (P = 0.054). There was a signi cant difference in MVC observed in all areas except for DCIS and FCD ± DIN (P < 0.001). We noted signi cant inverse correlations between MVC, HER2 expression, and the numbers of involved lymph nodes in invasive cancer and DCIS (P < 0.001). Most MVC were present in grade I, with the least frequent observed in grade III cases in the stroma of invasive cancer, DCIS and FCD ± DIN (P < 0.001). Conclusion: Angiogenesis can be observed before any signi cant myo broblastic changes in the pre-invasive breast lesions. The elevated content of myo broblasts in stroma of tumor; probably may be a worse prognostic factor and the steps from atypical epithelial hyperplasia to DCIS and then to the invasive carcinoma do not appear to be always part of a linear progression.
Analysis of stromal signatures in the tumor microenvironment of ductal carcinoma in situ
Breast Cancer Research and Treatment, 2009
Recent advances in the study of the tumor microenvironment have revealed significant interaction between tumor cells and their surrounding stroma in model systems. We have previously shown that two distinct stromal signatures derived from a macrophage (CSF1) response and a fibroblastic (DTF-like) response are present in subsets of invasive breast cancers and show a correlation with clinical outcome [1-3]. In the present study we explore whether these signatures also exist in the stroma of ductal carcinoma in situ (DCIS). We studied the signatures by both gene expression profile analysis of a publically available data set of DCIS and by immunohistochemistry (IHC) on a tissue microarray of DCIS and invasive breast cancer cases. Both the gene expression and immunohistochemical data show that the macrophage response and fibroblast expression signatures are present in the stroma of subsets of DCIS cases. The incidence of the stromal signatures in DCIS is similar to the incidence in invasive breast cancer that we have previously reported. We also find that the macrophage response signature is associated with higher grade DCIS and cases which are ER and PR negative, whereas the fibroblast signature was not associated with any clinicopathologic features in DCIS. A comparison of 115 matched cases of DCIS and invasive breast cancer found a correlation between the type of stromal response in DCIS and invasive ductal carcinoma (IDC) within the same patient for both the macrophage response and the fibroblast stromal signatures (P = 0.03 and 0.08, respectively). This study is a first characterization of these signatures in DCIS. These signatures have significant clinicopathologic associations and tend to be conserved as the tumor progresses from DCIS to invasive breast cancer.
Ductal carcinoma in situ: current morphological and molecular subtypes
Diagnostic Histopathology, 2012
The term ductal carcinoma in situ (DCIS) of the breast encapsulates a biologically, morphologically, clinically and genetically heterogeneous group of lesions. These have a wide spectrum of histological features but are characterized by a non-invasive proliferation of malignant epithelial cells confined to the parenchymal structures of the breast and thus contained within basement membrane-bound structures. Analysis at the molecular and genetic level has improved our understanding of these entities as non-obligate precursors of invasive breast cancer. It is clear that the linear progression model from normal epithelium through hyperplasia to atypical hyperplasia to DCIS to invasive breast cancer is inaccurate. Here we examine current methods for classifying DCIS and some recent molecular advances, including the impact of genetic profiling and immunohistochemistry, upon our understanding of current pathological definitions of DCIS.
Regulation of In Situ to Invasive Breast Carcinoma Transition
Cancer Cell, 2008
tumor progression that is poorly understood. Comparative molecular analysis of tumor epithelial cells from in situ and invasive tumors has failed to identify consistent tumor stage-specific differences. However, the myoepithelial cell layer, present only in DCIS, is a key distinguishing and diagnostic feature. To determine the contribution of non-epithelial cells to tumor progression, we analyzed the role of myoepithelial cells and fibroblasts in the progression of in situ carcinomas using a xenograft model of human DCIS. Progression to invasion was promoted by fibroblasts, but inhibited by normal myoepithelial cells. The invasive tumor cells from these progressed lesions formed DCIS rather than invasive cancers when re-injected into naïve mice. Molecular profiles of myoepithelial and epithelial cells isolated from primary normal and cancerous human breast tissue samples corroborated findings obtained in the xenograft model. These results provide the proof of principle that breast tumor progression could occur in the absence of additional genetic alterations and that tumor growth and progression could be controlled by replacement of normal myoepithelial inhibitory signals. SIGNIFICANCE There has been a dramatic improvement in our ability to detect DCIS, but our understanding of the factors involved in its progression is poorly defined. Our data suggest that a key event of tumor progression is the disappearance of the normal myoepithelial cell layer due to defective myoepithelial cell differentiation provoked by microenvironmental signals. Thus, myoepithelial cells could be considered gatekeepers of the in situ to invasive carcinoma transition and understanding the pathways that regulate their differentiation may open new venues for cancer therapy and prevention.
Bioscience Reports, 2014
The spread of mammographic screening programmes around the world, including in developing countries, has substantially contributed to the diagnosis of small non-palpable lesions, which has increased the detection rate of DCIS (ductal carcinoma in situ). DCIS is heterogeneous in several ways, such as its clinical presentation, morphology and genomic profile. Excellent outcomes have been reported; however, many questions remain unanswered. For example, which patients groups are overtreated and could instead benefit from minimal intervention and which patient groups require a more traditional multidisciplinary approach. The development of a comprehensive integrated analysis that includes the radiological, morphological and genetic aspects of DCIS is necessary to answer these questions. This review focuses on discussing the significant findings about the morphological and molecular features of DCIS and its progression that have helped to uncover the biological and genetic heterogeneity of this disease. The knowledge gained in recent years might allow the development of tailored clinical management for women with DCIS in the future. Key words: Breast cancer, cancer progression, Ductal carcinoma in situ (DCIS), epithelial cells, invasive breast carcinoma (IBC), microenvironment Cite this article as: Carraro, D. M., Elias, E. V. and Andrade, V. P . (2014) Ductal carcinoma in situ of the breast: morphological and molecular features implicated in progression. Biosci. Rep. 34(1), art:e00090.