The Morphological Characteristics And Differential Proteins Comparison Of The Cells Overlaying Ductal Disruption In Breast Carcinoma In Situ

Breast cancer is the top cancer in women both in the developed and the developing world. The incidence of breast cancer is increasing at a rate 3% in China. An follow up investigation shows that the recurrence rate of breast carcinoma in situ after surgical excision is low. But the recurrence rate of invasive carcinoma after surgical excision is high. Therefore, early detection in order to improve breast cancer outcome and survival remains the cornerstone of breast cancer control. The clinicopathological characteristics are complex. No single classification scheme has been universally accepted, and the mechanism of the processes from breast carcinoma in situ to invasive carcinoma remains unknown. This is the big obstacles to early detection and clinical treating strategy of breast carcinoma, so further research of the mechanism of the processes from breast carcinoma in situ to invasive carcinoma is significant for to find more diagnostic marks, to elevate early detection rate and provide more choices of clinical treating strategy.It is a commonly held belief that ductal carcinoma in situ is the precursor of the invasive breast carcinoma lesions. Some previous studies demonstrate that pre-invasive breast tumors have been found to be associated with focal myoepithelial cell layer disruptions and the cells overlaying focal myoepithelial cell layer disruptions are significant different from other adjacent tumor cells within the same duct, show more inmmuophenotypes and genetic mutations related to the tumor malignancy, such as ER nagitive, c-erb-B2 up-regulation, high proliferation rate, genetic instability, and loss of heterozygous. Based on these finding, it is speculated that these tumor cells may be the earliest cells with invasive and metasitic ability, may represent the precursor of invasive breast lesion. Previous series studies consistently shows that the cells overlaying ductal myoepithelial cell layer are associated with tumor invasion, metastasis and poor prognosis, and can be a indepent prognostic factor.For further studding the ultrastructure and characteristics of stromal digestion, cell adhesion, cell motility and proteomics of the cells overlaying ductal wall disruption, we checked 3325 cases documents of breast cancer patients. Screening 158 cases performed formalin fixed, paraffin embedded tumor samples that harboring ductal wall disruptions transforming ultra-section. Under transmission electron microscope, it shows that the tumor cells overlying FMCLDs had darkly stained nuclei and cytoplasm, with elongated nuclei. Compared to these cells, the adjacent tumor cells within the same duct were rounded, with weakly stained nuclei and cytoplasm, with high electronic density at the regions of membrane contact. This demonstrated that the membrane junction was tight between in situ tumor cells Immuohistochemically, the expressions of MMP-2 and MMP-9 are higher in this cell cluster than adjacent tumor cells within same duct, and TIMP-2 same as this. E-cadherin, and focal adhesion kinase (FAK) in tumor cells overlying FMCLDs were higher than those within the corresponding duct. Integrinβ1 staining was detected only in a small number of the tumor cells overlying FMCLDs. Vinculin staining was weak (18%) or not detected (82%), and no expression was found in tumor cells within the corresponding duct or in pure isolated DCIS. By contrast, the expression levels of talin, vinculin and integrinβ1 in invasive tumors was distinctly higher than that in DCIS, and the expression of FAK and E-cadherin was lower. Under electron microscopy, the tight junctions between tumor cells overlying FMCLDs were reduced compared to the adjacent tumor cells in the lumen. These results indicate that the tumor cells overlying FMCLDs are likely to represent the specific precursors of invasive breast lesions. By PF 2D system, 33 differential protein points were identified. 140 candidate proteins were identified by ESI-TOF-MS/MS system. Random to choice two candidate proteins, AKR1B10 and DHRS7, performed Immunohistochemical staining, we found that these two proteins expression level in cell overlaying ductal wall disruption are significant different with the adjacent tumor cells within same duct. Previous same studies demonstrated the AKR1B10 and DHRS7 proteins over expression are associated with poor prognosis. Our finding demonstrated that the cells overlaying ductal wall disruption have more malignancy than the adjacent tumor cells within same duct, and confirm the proteomic results are trustworthy.Our findings may also facilitate the identification of specific targets for further molecular profiling, which will more completely characterize this important cell population.