Matrix Histology And Biomechanics Research Using Shear Wave Elastic Modulus In Breast Cancer

ObjectiveBreast cancer is one of the most common cancers in the world,and it is the biggest cause for cancer-related death.The components of extracellular matrix(ECM)widely regulate the biological behavior of tumors.This study intends to study the changes of ECM components in breast tumors by quantitative or qualitative methods,and to study the correlation between ECM and shear wave elastic modulus,which will provide strong support for the research on the regulation of ECM in breast cancer.Methods113 breast lesions from 111 patients in the department of ultrasonography of this institute were performed elastography,all lesions performed vacuum-assisted Biopsy(VAB)or surgery and harvested confirmed pathology result.All patients were divided into two groups,in which 54 were in the malignant group and 59 in the benign group.The elastic modulus of the tumor(Emax),minimum(Emin),average elastic modulus(Emean),and elasticity ratio between lesions and surrounding parenchyma(Eratio)were deternined.Collagen fibers and elastic fibers were stained by Van Gieson method.Image-Pro Plus 5.1 Software was used to quantitatively analyze collagen fiber area.Computer graphic analysis was performed under detailed measurement settings by a board-certified pathologist.5 fields under high magnification(x 400)were randomly selected for each slide and the mean value was calculated.The expression of laminin and fibronectin was analyzed by immunohistochemistry.Results1.Malignant group included invasive ductal carcinoma(n=46),ductal carcinoma in situ(DCIS)(n=7)and invasive lobular carcinoma(ILC)(n=1).The benign group consisted of 40 fibroadenomas,13 fibroadenomas and 6 sclerosing adenosis.2.Modulus value of Emax,Emean and Eratio(30.0 11.1 kPa,50.1 17.5 kPa,2.25 0.54 kPa)in the benign group were smaller than those in the malignant group(63.1 17.9kPa,122.0 26.6kPa,3.88 0.77kPa),and there was no significant difference in Emin between the two groups(p>0.05).3.The type ? collagen fibers in the extracellular matrix of the breast tumor were stained red under the microscope.In the malignant group,the occupied area by quantitative analysis was 8718.6-19122.1 ?m2,which in benign group was 4419.9-12820.7 ?m2.The proportion of type ? collagen fibers in the extracellular matrix of the malignant group was significantly higher than that of the benign group(13757.2 2926.6 vs 9717.2 2548.1 ?m2,p<0.05).In the malignant group,the occupied area of the elastic fibers using quantitative analysis was 6776.3?0069.9 ?m2.In the benign group,the area of which was 4760.0?13950.7?m2.The proportion of elastic fibers in the extracellular matrix of tumor in the malignant group was significantly higher than that in the benign group(14384.42853.7 vs 9257.5 2392.8 ?m2,p<0.05).The nuclei of the interstitial cells were stained brown after immunohistochemical staining.In the malignant group,fibronectin expression was positive expressed in all cases,while in the benign group,32 cases were positive and 27 cases were negative expressed.The expression between the two groups was statistically different(p<0.05).In the malignant group,laminin expression was positive in 48 cases and negative in 6 cases.In the benign group,54 cases were positively expressed and 5 cases were negatively expressed,and there was no statistical difference between the two groups(p>0.05).4.Univariate linear regression analysis showed that collagen fiber area,elastic fiber area and Emax were positively correlated(r=0.439,r=0.709,P<0.001);The t-test of independent samples showed that the elastic modulus of the patients with positive fibronectin expression increased,while the Emax in patients with negative expression was lower,showing a statistical difference(p<0.05).There was no significant difference in laminin between the two groups(p>0.05).Stepwise regression method was used to conduct multiple linear regression analysis.The optimal model affecting the Emax in breast tumors was:Emax=-15.200+0.006*elastic fiber area+0.002*collagen fiber area+10.337* fibronectin expression characteristics.The standard partial correlation coefficients of the dependent variables of elastic fiber,collagen fiber and fibronectin were 0.655,0.174 and 0.136,respectively.ConclusionsThe extracellular matrix components between benign and malignant breast tumors are obviously different,this study found that stromal components like collagen fiber,elastic fiber content were more deposited in cancers,fibronectin expressed in all breast cancer,while it negative expressed in 27 benign cases.In this study,the differences of major proteins in extracellular matrix between benign and malignant breast tumors were compared,and the regulatory effects of various proteins in the development of breast cancer were preliminarily analyzed.Through the elastographic characteristics research of benign and malignant breast lesions,the correlation was clear between tumor stiffness and matrix components changes,this study found that the biggest factor regulates the Emax or tumor stiffness is the elastic fiber,followed by collagen and fibronectin.