According to Kononen and colleagues
] tissue microarrays (TMAs) were developed to allow high throughput analysis of protein expression in tumors tissues and many authors agree that they can be used to validate biomarkers
]. Here, β1 integrin expression and its relationship with survival of patients with IDC were analyzed in a tissue microarray.
During the last years a number of reports have linked integrins to tumorigenicity ranging from local tumor growth to metastasis
] and it is well documented that integrins contribute to migration and invasion of cancer cells
]. β1 integrin is the most widely expressed integrin in cells and has been suggested to play a role in predicting the clinical course and prognosis of several types of cancers
]. However, Brakebusch and colleagues
] argue that it is not surprising that some studies link tumorigenicity to β1 integrin in the form of down- or up-regulated expression. For example, according to Guo and colleagues
] β1 integrin is the most abundantly expressed integrin in Non-small-cell lung carcinoma and other authors
] founded that its expression has been associated with lymph node metastasis in the same type of cancer. Although Kren and colleagues
] noted that the low expression of β1 integrin promoted tumor cells dissemination in a mouse model of pancreatic β cell carcinogenesis.
In regard to breast cancer, some studies have reported that decreased β1 integrin expression was associated with characteristics of more aggressive disease
], while others observed that the high expression of β1 integrin is associated with decrease survival
]. Berry and colleagues
] and Petricevic and co-workers
] verified no significant correlation with β1 integrin expression and survival of patients with breast carcinoma. Then, it is possible to realize that there are controversies in the studies concerning the expression of this protein as well as its relation with survival rate in patients with breast cancer.
We choose the same score used by Yao and colleagues
] based on the level of signal and percentage of tumor cells expressing the signal. Here, we provide evidences that β1 integrin high expression (2+ and 3+) can be predictive of response and has impact on specific-free survival in patients with breast cancer. Ours findings did not relate β1 integrin with metastasis free survival. Some authors suggested that β1 integrin is important but not essential for metastasis
]. All these findings are in accordance with previous reports in different types of cancer
], including previous studies that showed that β1 integrin inhibition induces apoptosis in breast cancer cells
The basement membranes are reservoirs for growth factors
] and it is well known that specific integrins can activate specific FGRs
]. For example, Hayashida and colleagues
] founded that β1 integrin are dependently linked with TGF-β1, and that knocking β1 integrin down enhances the cell collagen production trough TGF-β1. Nowadays, it is well known that the interaction between FGRs and integrins can regulate cell survival and proliferation and supporting tumor growth
Some studies linked β1 integrin with members of the FGR family including VEGF
]. This can promote angiogenesis through up-regulation and/or activation of integrins
]. Other study demonstrated that VEGF activity is dependent on β1 integrin function. In this study the authors founded that the knockout of β1 integrin in embryonic stem cells, neither the proliferation of the endothelial cells nor sprouting of blood vessels occurred, suggesting that VEGF had no effect in β1-null embryoid bodies
]. More interestingly Lee and colleagues
] with in vitro
studies, with human brain microvascular endothelial cells, showed that blocking β1 integrin, all processes of angiogenesis was inhibited (adhesion, migration, and capillary morphogenesis) and they also suggested that the α6β1 integrin is closely related to the metastasis of breast cancer cells to the brain.
Studies have demonstrated that some oncogenes require specific integrins for tumorigenicity. Integrins are not oncogenic molecules, but some of them can cooperate with oncogene to initiate growth, invasion and progression of the cancer
]. In a transgenic mouse model of human breast cancer some authors founded that β1 integrin mediates the initiation of mammary tumorigenesis that is driven by the polyoma middle T oncoprotein
Recent data suggest a relationship between HER-2 and β1 integrin. Shimizu and colleagues
], in a study with breast cancer cell line, suggested that the α6β1 integrin inhibits HER-2 signals by proteolytic cleavage of the cytoplasmic domain of HER-2 and this could also contribute to the regulation of tumor growth. Other authors
] demonstrated that even under adverse conditions such as hypoxia and chemotherapeutic treatments there is a strong regulation between HER-2 signaling stimulating the expression of the integrin α5 and β1 which promotes tumor cell survival.
In the present study, we found a relationship between low expression of β1 integrin and negativity for HER-2 demonstrating some evidence that this subgroup of patients might have a less aggressive phenotype. Besides, we showed that patients who had high β1 integrin expression showed the poor prognostic.
Angiogenesis is induced by VEGF through its interaction with receptors expressed primarily on the vascular endothelial cell membrane
] and is well known that tumors depend largely on effective angiogenesis
]. The amplification of the proto-oncogene HER-2 is observed in approximately 15–30% of all breast cancer samples and has been correlated with a shorter survival
]. An important aspect of the involvement of β1 integrin in angiogenesis and tumorigenicity is the potential implication for tumor treatment
]. This study shows that β1 integrin expression on tumor cells actually promote tumor progression and acts as a tumor enhancer. In addition, our results indicate that both expression of the β1 integrin and its association with HER-2 and VEGF may be useful in targeted therapies for patients with breast cancer.
One of the main focuses concerning breast cancer has been the identification of the molecular alterations associated with the different stages of the progression disease. According to Bombonati and Sgroi  the current model of human breast cancer progression proposes a linear multi-step process which initiates as flat epithelial atypia, progresses to atypical ductal hyperplasia, evolves into DCIS and culminates in the potentially lethal stage of IDC. In our study we do not found association with the expression of β1 integrin in IDC and DCIS. 67,1% of the IDC cases were negative for β1 integrin and 67,2% were negative in DCIS cases, with no significant relation probably due to the limited number of cases.