Correlation of α2ß1 Integrin Expression with Histological Type and Hormonal Receptor Status in Breast Carcinomas

Lanzafame, Salvatore; Emmanuele, Carmela; Torrisi, Antonietta

doi:10.1016/s0344-0338(96)80045-8

Cited by 19 publications

(15 citation statements)

References 21 publications

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“…In regard to breast cancer, some studies have reported that decreased β1 integrin expression was associated with characteristics of more aggressive disease [39,40], while others observed that the high expression of β1 integrin is associated with decrease survival [20]. Berry and colleagues [41] and Petricevic and co-workers [21] verified no significant correlation with β1 integrin expression and survival of patients with breast carcinoma.…”

Section: Discussionmentioning

confidence: 99%

Beta 1 integrin predicts survival in breast cancer: a clinicopathological and immunohistochemical study

et al. 2012

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BackgroundThe main focus of several studies concerned with cancer progression and metastasis is to analyze the mechanisms that allow cancer cells to interact and quickly adapt with their environment. Integrins, a family of transmembrane glycoproteins, play a major role in invasive and metastatic processes. Integrins are involved in cell adhesion in both cell-extracellular matrix and cell-cell interactions, and particularly, β1 integrin is involved in proliferation and differentiation of cells in the development of epithelial tissues. This work aimed to investigate the putative role of β1 integrin expression on survival and metastasis in patients with breast invasive ductal carcinoma (IDC). In addition, we compared the expression of β1 integrin in patients with ductal carcinoma in situ (DCIS).MethodsThrough tissue microarray (TMA) slides containing 225 samples of IDC and 67 samples of DCIS, β1 integrin expression was related with several immunohistochemical markers and clinicopathologic features of prognostic significance.Resultsβ1 integrin was overexpressed in 32.8% of IDC. In IDC, β1 integrin was related with HER-2 (p = 0.019) and VEGF (p = 0.011) expression and it had a significant relationship with metastasis and death (p = 0.001 and p = 0.05, respectively). Kaplan-Meier survival analysis showed that the overexpression of this protein is very significant (p = 0.002) in specific survival (number of months between diagnosis and death caused by the disease). There were no correlation between IDC and DCIS (p = 0.559) regarding β1 integrin expression.ConclusionsConsidering that the expression of β1 integrin in breast cancer remains controversial, specially its relation with survival of patients, our findings provide further evidence that β1 integrin can be a marker of poor prognosis in breast cancer.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/6652215267393871

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Section: Discussionmentioning

confidence: 99%

Beta 1 integrin predicts survival in breast cancer: a clinicopathological and immunohistochemical study

et al. 2012

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“…It is plausible that a relative loss or gain of h 1 integrin expression in malignant tissue could occur relative to the normal intact epithelium. Previous studies of human breast tumors have reported that, compared with expression in normal tissue seen primarily in the myoepithelial cell layer of breast ducts, decreased h 1 integrin expression was associated with characteristics of more aggressive disease (26)(27)(28)(29). Conversely, increased h 1 integrin signaling has been shown to promote tumorigenesis by facilitating growth factor receptor activity (4,30) and inhibition of h 1 integrin has been shown to abrogate metastasis (31,32).…”

Section: Discussionmentioning

confidence: 99%

Increased β1 Integrin Is Associated with Decreased Survival in Invasive Breast Cancer

Yao

Zhang

Chen³

et al. 2007

Cancer Research

215

168

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Aberrant microenvironments and loss of balance in cellextracellular matrix signaling are associated with breast cancer invasion, metastasis, and resistance to therapy. We have recently shown that increased B 1 integrin signaling is involved in malignant progression and that inhibitory antibody to B 1 integrin leads to selective apoptosis and decreased proliferation in three-dimensional cultures and in xenograft models of breast cancer in vivo. To investigate the clinical importance of these findings, in the present study we examined the expression of B 1 integrin and extracellular B 1 integrin ligands fibronectin and laminin-1 in a cohort of 249 breast cancer patients who had a median follow-up of 8.4 years. Among the 149 scorable cases, the highest B 1 integrin intensity score (3+ versus 0-2+) was associated with significantly decreased 10-year overall survival of 48% versus 71% (P < 0.03) and decreased disease-free survival of 50% versus 80% (P < 0.05). Importantly, high fibronectin expression was associated with decreased overall and disease-free survival on univariate analysis (P < 0.04) and B 1 integrin intensity score was significantly correlated with fibronectin expression (Kendall's tau-b = 0.19; P = 0.03). In a multivariate Cox proportional hazards model, B 1 integrin intensity score remained a significant independent predictor of overall survival [hazard ratio (HR), 1.69; 95% confidence interval (95% CI), 1.19-2.38; P < 0.003] and disease-free survival (HR, 1.87; 95% CI, 1.21-2.88; P < 0.005). These findings show that B 1 integrin expression has potential prognostic value in invasive breast cancer and that coexpression of fibronectin may help identify patients with more aggressive tumors who may benefit from targeted therapy. [Cancer Res 2007;67(2):659-64]

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“…High levels of integrin ␣2␤1 (collagen͞laminin receptor) have been found on epithelial cells from benign hyperplastic͞neoplastic mammary glands, but they are very reduced or lost on malignant cells of breast carcinoma. The loss of the integrin ␣2␤1 expression and the increased invasiveness of neoplastic cells correlates with estrogen and progesterone receptor negativity (22). The promoter region of integrin ␣2 contains six Sp1-binding sites, consensus-binding sites for AP-1 and -2 complexes, and two potential estrogen responsive elements (EREs) (23).…”

Section: Discussionmentioning

confidence: 99%

Involvement of estrogen receptor β in terminal differentiation of mammary gland epithelium

Förster

Mäkelä

Wärri

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

219

154

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The mammary glands of prepubertal estrogen receptor (ER)␤؊͞؊ mice are morphologically indistinguishable from those of WT littermates. It appears that, although ER␤ is expressed in the mouse mammary gland, it is not involved in ductal growth of the gland. In this study, we examined the possibility that ER␤ has a role in the differentiated function of the mammary gland. Pregnancy is rare in ER␤؊͞؊ mice, but an intensive breeding program produced seven pregnant ER␤؊͞؊ mice, of which five did not eat their offspring and continued to successful lactation. Histomorphological comparison of lactating glands revealed that alveoli were larger and there was less secretory epithelium in ER␤؊͞؊ than in WT mice. Ultrastructural analysis showed abundant milk droplets and normal apical villi in the luminal epithelial cells, but the extracellular matrix and lamina basalis were reduced, and very frequently the interepithelial cell space was increased. Levels of the adhesion molecules, E-cadherin, connexin 32, occludin, and integrin ␣2 were reduced, and no zona occludens was detectable. In addition, there was widespread expression of the proliferation marker, Ki-67, in luminal epithelial cells in ER␤؊͞؊ but not in WT mice. These findings suggest a role for ER␤ in organization and adhesion of epithelial cells and hence for differentiated tissue morphology. We speculate that, because a reduced risk for breast cancer is conferred on women who breast-feed at an early age, ER␤ could contribute to this risk reduction by facilitating terminal differentiation of the mammary gland.lactation ͉ cadherin ͉ integrin ͉ tight junction T argeted disruption of estrogen receptor (ER)␤ in mice has revealed that this is a functional receptor in both males and females and that, in addition to its role in reproductive functions (1), it is also important in the cardiovascular (2) and central nervous systems (3). Female mice homozygous for the mutated ER␤ gene (ER␤Ϫ͞Ϫ mice) have been described as subfertile or infertile (4, 5). The ovarian defect is due to early atresia of antral follicles and failure to ovulate. As a result, corpora lutea are rare in ER␤Ϫ͞Ϫ mouse ovaries (6).Prepubertal ER␤Ϫ͞Ϫ females appear to have a normal mammary histology (5) with unaffected ductal outgrowth of the mammary gland anlage. However, because corpora lutea are rare, little progesterone is produced in the ovaries and, in contrast to their WT littermates, ER␤Ϫ͞Ϫ mammary glands fail to develop ductal side branches and alveoli after puberty. On administration of progesterone, side branching occurs, and mammary glands of ER␤Ϫ͞Ϫ mice appear morphologically indistinguishable from those of their WT littermates (7). As judged by nursing behavior and growth of their pups, ER␤Ϫ͞Ϫ mice have previously been reported to lactate effectively (5). In contrast, in female mice lacking aromatase (8) or ER␣ (9), mammary glands fail to develop beyond the prepubertal stage. From these studies, it has been concluded (5) that estrogen, acting through ER␣ but not through ER␤, is essential for norm...

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Correlation of α2ß1 Integrin Expression with Histological Type and Hormonal Receptor Status in Breast Carcinomas

Cited by 19 publications

References 21 publications

Beta 1 integrin predicts survival in breast cancer: a clinicopathological and immunohistochemical study

Beta 1 integrin predicts survival in breast cancer: a clinicopathological and immunohistochemical study

Increased β1 Integrin Is Associated with Decreased Survival in Invasive Breast Cancer

Involvement of estrogen receptor β in terminal differentiation of mammary gland epithelium

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