Morphologic, molecular and microenvironment factors associated with stromal invasion in breast ductal carcinoma in situ: Role of myoepithelial cells (original) (raw)
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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.
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.
Invasion in breast lesions: the role of the epithelial-stroma barrier
Histopathology, 2017
Despite the significant biological, behavioural and management differences between ductal carcinoma in situ (DCIS) and invasive carcinoma of the breast, they share many morphological and molecular similarities. Differentiation of these two different lesions in breast pathological diagnosis is typically based on the presence of an intact barrier between the malignant epithelial cells and stroma, namely the myoepithelial cell (MEC) layer and surrounding basement membrane (BM). Despite being robust diagnostic criteria, the identification of MECs and BM to differentiate in situ from invasive carcinoma is not always straightforward. The MEC layer around DCIS may be interrupted and/or show an altered immunoprofile. MECs may be absent in some benign locally infiltrative lesions such as microglandular adenosis and infiltrating epitheliosis, and occasionally in non-infiltrative conditions such as apocrine lesions, and in these contexts this does not denote malignancy or invasive disease with...
Anticancer research
Numerous experimental studies have described the capacity of myofibroblasts to stimulate mammary cancer cells in a paracrine manner. Until now, the prognostic significance of myofibroblasts present in breast cancer has not been examined. In paraffin sections, originating from 45 patients with primary invasive breast cancer, immunohistochemical reactions were performed using antibodies directed against smooth muscle actin, Ki-67, VEGF, bFGF and UPA. The cases with higher content of myofibroblasts in the tumour tissue manifested higher grade, more pronounced expression of Ki-67, VEGF and bFGF and shorter overall survival and relapse-free survival. The present study for the first time documents the unfavourable prognostic significance of myofibroblasts in tissues of invasive ductal mammary carcinomas.
Journal of Clinical Pathology, 2004
Background: Recent studies have reported CD10 expression in myoepithelial cells (MEC) of the breast, supporting its use as a marker to help distinguish invasive breast carcinoma (IC) from ductal carcinoma in situ (DCIS). Aim: To compare the effectiveness of CD10 with smooth muscle myosin heavy chain (SMMHC) in the detection of MEC in benign and malignant breast lesions. Methods: Histological material from 25 patients with DCIS and 21 with IC were immunostained for CD10 and SMMHC. Staining was scored on a scale of 0 to 3+ (0, no staining; 3+, intense) and the staining distribution was documented as focal, partial, or circumferential. Results: Uniform, 3+ circumferential CD10 and SMMHC staining of MEC was seen in normal breast ducts and lobules, and in ducts and acini involved in sclerosing adenosis and apocrine metaplasia. In an analysis of total ducts involved by DCIS, 3+ circumferential staining was seen in 65 of 366 ducts (17.7%) stained for CD10 versus 190 of 396 ducts (48%) stained for SMMHC. MEC were not detected immunohistochemically in 116 of 366 ducts (31.7%) with anti-CD10 and 50 of 396 (12.7%) with anti-SMMHC. In contrast, all ICs were negative for both CD10 and SMMHC. Focal background staining of stromal myofibroblasts was seen with both CD10 and SMMHC, but CD10 showed a higher rate of nonspecific staining of epithelial cells. Conclusion: Although CD10 can aid in the distinction between IC and DCIS, SMMHC is a more sensitive and specific marker of MEC and shows less heterogeneity of immunostaining patterns.
Revista brasileira de ginecologia e obstetrícia : revista da Federação Brasileira das Sociedades de Ginecologia e Obstetrícia, 2013
PURPOSE: To compare the prognostic and predictive features between in situ and invasive components of ductal breast carcinomas. METHODS: We selected 146 consecutive breast samples with ductal carcinoma in situ (DCIS) associated with adjacent invasive breast carcinoma (IBC). We evaluated nuclear grade and immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), cytokeratin 5/6 (CK5/6), and epidermal growth factor receptor (EGFR) in both components, in situ and invasive, and the Ki-67 percentage of cells in the invasive part. The DCIS and IBC were classified in molecular surrogate types determined by the immunohistochemical profile as luminal (RE/PR-positive/ HER2-negative), triple-positive (RE/RP/HER2-positive), HER2-enriched (ER/PR-negative/HER2-positive), and triple-negative (RE/RP/HER2-negative). Discrimination between luminal A and luminal B was not performed due to statistical purposes. Correlations between the categories in the two groups were made using the Spearman correlation method. RESULTS: There was a significant correlation between nuclear grade (p<0.0001), expression of RE/RP (p<0.0001), overexpression of HER2 (p<0.0001), expression of EGFR (p<0.0001), and molecular profile (p<0.0001) between components in situ and IBC. CK 5/6 showed different distribution in DCIS and IBC, presenting a significant association with the triple-negative phenotype in IBC, but a negative association among DCIS. CONCLUSIONS: Our results suggest that classical prognostic and predictive features of IBC are already determined in the preinvasive stage of the disease. However the role of CK5/6 in invasive carcinoma may be different from the precursor lesions.