Clinical Application And Pathological Basic Research Of Acoustic Radiation Force Impulse (ARFI) Technology In Breast Lesions And Sonographic Features Of Breast Carcinomas In BRCA2 Gene Mutation Carriers

Part ? Clinical Application Research of ARFI Technology in Breast Lesions and Analysis of the Molecular Biology Factors Influencing ARFIObjective To evaluate the application value of acoustic radiation force impulse(ARFI)technology in the differentiation of breast lesions and screening the best quantitative diagnostic parameter,compare the diagnostic performance of BI-RADS applied separately and BI-RADS combined with ARFI technique in breast lesions,evaluate the application value of ARFI technique in BI-RADS category 4A lesions,and the molecular biological factors which impact the shear wave velocity(SWV)within breast carcinomas were analyzed.Materials and Methods A total of 233 breast lesions in 230 women were enrolled and evaluated by using BI-RADS and ARFI techniques.The area ratio(AR),SWV of the lesion inner regions(SWVi),SWV of lesion boundary zone(SWVb),SWV of normal breast fat shear wave velocity(SWVf),SWV of normal breast gland(SWVg),SWVraf(SWVi/SWVf),and the SWVrag(SWVi/SWVg)were measured and calculated by VTQ(Virtual Touch Tissue Quantification)and VTI(Virtual Touch Tissue Imaging)models of ARFI.ROC curve was used to determine the best cut-off value of ARFI quantitative parameters in the differentiation of breast lesions.SWVi was applied to downgrade BI-RADS category 4A lesions to category 3 and the application value of ARFI in BI-RADS category 4A lesions was evaluated.Univariate and multiple linear regression statistical methods were used to analyze the molecular biological factors that impact the SWVi.Results(1)AR,SWVi,SWVb,SWVraf,and SWVrag of malignant small breast solid lesions were all significantly larger than that of the benign ones(all P<0.05).SWVb of breast chronic inflammatory lesion or intraductal papilloma was larger than that of fibroadenoma(P=0.004,P=0.027).Both of SWVi and SWVb of breast infiltrating ductal carcinoma(IDC)were larger than those of ductal carcinoma in situ(DCIS)(P=0.000).Though the SWVb of breast mucinous carcinoma was larger than SWVi(P=0.000),SWVi was smaller than that of IDC(P=0.000).(2)The best cut-off value of AR,SWVi,SWVb,SWVrag,SWVraf was 1.19,3.42 m/s,2.86 m/s,2.40 and 3.16,respectively.The diagnostic sensitivity of AR is the highest,and the diagnostic specificity of SWVi is the highest.The diagnostic performances of ARFI quantitative parameters were similar,but all of them were lower than BI-RADS.When applying BI-RADS combined with ARFI technique to diagnose breast carcinomas,the sensitivity,specificity and area under the curve(AUC)could be up to 88.3%,92% and 0.950,respectively.(3)By applying the threshold of SWVi only to BI-RADS category 4A lesions,86.9% benign lesions were downgrade to category 3,thus avoiding unnecessary biopsies,but the malignant rate of category 3 lessons was up to 4.3%.By applying a conservative value of 1.68m/s to downgrade category 4A lesions,20.0% benign lesions were downgrade without the raise of malignant rate in category 3 lessons.(4)After multivariate analysis,only lesion size and histological grade were independently associated with SWVi(P<0.05).Conclusions(1)Among ARFI quantitative parameters,AR had the highest diagnostic sensitivity SWVi had the highest diagnostic specificity.Although the diagnostic performances of ARFI parameters were similar,they were all lower than that of BI-RADS.(2)Breast lesions with different pathological types had different ARFI characteristics.The diagnostic specificity was significantly improved when BI-RADS combined with ARFI technique.ARFI technology was a powerful supplement to conventional ultrasound examination.When applying SWVi to adjust BI-RADS category 4A lesions,a conservative point was recommend to used to decrease excessive tissue biopsies without increasing false negative cases.(3)The size and histological grade of invasive breast carcinomas were independently related to SWVi.Part ? Preliminary Study on the Histopathological Basis of Ultrasound Elastography in Breast LesionsObjective To assess the relationship among ultrasonic image features,T1 stage IDC elastographic features and collagen fibers content.Then assess the relationship between SWVi of small breast lessons and the characteristics of collagen,cell nucleus and tumor microvessel density(MVD).Materials and Methods(1)A total of 102 IDC lessons were enrolled and evaluated by using BI-RADS and strain ultrasound elastography.Masson's trichrome staining was applied to stain collages fibers.Image analysis software of IPP 6.0 was applied to quantify collagen fibers content.(2)A total of 51 IDC lessons were enrolled and evaluated by using ARFI technology.Hematoxylin eosin and Masson's trichrome staining were applied to stain cell nucleus and collages fibers,respectively.The nucleus and collagen content were quantified by IPP 6.0 software.Immunohistochemical technique was used to stain microvessels that was quantified by manual counting.Results(1)Among T1 stage IDC,the content of collagen in the tumor with unclear boundary is higher than that of the clear boundary(P=0.038).Collagen content in the tumor with posterior echo reduction was higher than that of the mass with the posterior echo enhancement(P=0.000).Collagen content was significantly different in different BI-RADS tumors(P=0.009),and with the increase of classification level,the collagen content increased gradually.Tumor with different elasticity score had different collagen content and the collagen content was positively correlated with elasticity score(r=0.462,P=0.000).(2)The cell nuclear content,MVD and SWVi within breast fibroadenoma were all significantly lower than those of T1 IDC(all P = 0.000),but there was no significant difference of collagen content between the two kinds of tumors(P = 0.123);the morphology and distribution features within fibroadenoma had clear differences from those within IDC.Though there had a statistical difference of collagen content between IDC in different SWVi groups(P = 0.033),the correlation analysis showed that the nucleus,collagen content and MVD were all not related to tumor SWVi(all P>0.05).Conclusions There had a close relationship of collagen content of T1 stage IDC with tumor elastic score and SWVi,which revealed the pathologically structural bases for SWVi among different IDC.The IDC with higher collagen content was more inclined to show malignant characteristics in the ultrasound image.The SWVi of fibroadenoma was smaller than that of IDC,but the collagen content was higher than that of IDC,though there was no significant difference(P = 0.123),preliminarily infers their differences stiffness might be related to the morphology and distribution of the internal collagen fibers.Part ? The Study of the Pathological and Sonographic Features of Breast Carcinomas in BRCA2 Gene Mutation CarriersObjective To compare the pathological,molecular biological,conventional sonographic and ARFI characteristics of breast carcinomas with and without BRCA1 gene mutations,in order to find the BRCA2 gene mutation tendency imaging features,and initially explored the value of ultrasonic technology as a tool to screen BRCA2 gene mutation-associated breast cancer.Materials and Methods(1)Peripheral venous blood of 394 breast cancer patients,who had hospitalized in gastrointestinal and gland surgery department of our hospital and 30 female healthy volunteers over the same period were collected.For the mutation in tenth exon and eleventh exon of the BRCA2 gene occurred more frequently,we designed 9 pairs of primers.The gene mutation was detected by direct sequencing.Among 394 breast carcinoma patients,a total of 300 tumors had complete pathologic findings,283 tumors had complete conventional sonography,and 143 tumors had satisfactory ARFI results.Results(1)Among 394 breast cancers,a total of 17 BRCA1 mutations were found,including 11 missense mutations,4 same sense mutations and 2 frame shift mutations.The prevalence of BRCA2 gene mutation was 4.3%.There was no BRCA2 gene mutation found in 30 female healthy volunteers.(2)The most common pathological type was IDC in the mutation group tumors,followed by DCIS.There had a significantly difference in tumor histological grade between mutation group and non-mutation group(P = 0.035),and the proportion of the histological grade 3 in mutant group was significantly higher than that in non mutation group(43.8% vs.21.3%,P = 0.036).In the mutation group,there were 68.8% of tumors with ER positive,12.5% of tumors with HER-2 negative,18.7% of tumors with Base-like type,and 56.2% of tumors with axillary lymph node metastasis.(3)Compared with tumors in non mutation group,the sonographic characteristics,including regular shape,easily circumscribed edge,and BI-RADS category?4B were relatively common,but the sonographic characteristic of posterior echo reduction was relatively few to see.There was no significant difference of sonographic characteristics between the two groups(all P>0.05).(4)Among breast carcinomas sized ? 20.0mm,the tumor SWVi in mutation patient was significantly lower than that in non-mutation patient(3.96±2.05 m/s vs.2.31±0.45 m/s,P=0.019)?Conclusions(1)The histopathological features of breast cancer with BRCA2 gene mutation were as follows,ER positive and axillary lymph node metastasis were common to see,HER-2 over expression and base-like types were few to see.Compared with non-mutation breast cancers,the percentage of histological grade of 3 was significantly higher.(2)There was no specific sonographic characteristic in BRCA2 gene mutation breast cancer.Comparing with non-mutation breast cancers,regular shape,easily circumscribed edge,without posterior echo reduction and BI-RADS category?4B were more common to see,and the SWVi of tumor(sized?20.0mm)in BRCA2 gene mutation breast cancer was significantly lower than that in non-mutation breast cancers.Thus,the misdiagnosis rate of ultrasonic diagnosis might be higher in BRCA2 gene mutation breast cancer than that in non-mutation breast cancers.