The Preliminary Assessment Of Characteristics Of Conventional Ultrasound And Contrast-enhanced Ultrasonography Of Infiltrating Ductal Carcinoma Of The Breast And The Prognostic Markers In Molecular Pathology Correlation

Part I: The characteristics of conventional ultrasound and contrast-enhanced ultrasound sonography of infiltrating ductal carcinoma of the breast in the consistency evaluation of different seniority radiologistObjective: Retrospectively analyzing the characteristics of conventional ultrasound and contrast-enhanced ultrasound sonography of infiltrating ductal carcinoma of the breast and statistically analyzing the interpretation results of IDC ultrasonographic characteristics of different doctors to screen the characteristics of conventional ultrasound and contrast-enhanced ultrasound sonography of IDC with good interpretation of the results consistency for the second part of the study.Materials and methods: The ultrasonic imaging data of 193 cases of IDC patients confirmed by histopathology were selected. The patients in the group of this research had no past treatment history of IDC and all had underwent conventional ultrasound and contrast-enhanced ultrasound before surgery and biopsy. Conventional ultrasound and ultrasound angiography of IDC, data acquisition, storage and postprocessing were conducted by a deputy director of physicians in breast ultrasound according to the <The routine medical treatment in Peking Union Medical College Hospital: routine diagnosis and treatment of the department of ultrasound>(The Second Edition) breast examination standard and the eighth chaptor of <Prenatal ultrasound and contrast-enhanced ultrasound guide> that "Guidelines for the clinical application of breast ultrasound angiography" published in 2013 by ultrasound Doctor Association of Chinese Medical Doctor Association. Breast imaging reporting and data system of the 2013 Edition and breast lumps of conventional ultrasound and contrast-enhanced ultrasound sonographic features in the above guidelines were selected as the observation index of IDC ultrasonography(characteristics) in this study, which include that:(1) Conventional ultrasound: The maximum diameter, morphology, internal micro calcium stove, hyperechoic halo, spicule sign and features of posterior echo of the section;(2) Ultrasound angiography: distribution, enhanced level and dirction, enhanced mode by time-intensity curve and egression method of contrast medium. The sonographic characteristics of conventional ultrasound and contrast-enhanced ultrasound in each tumor of IDC were analyzed by 3 different doctors(engaged in ultrasound diagnosis in 3 years, 5 years and 8 years) and the results were interpretated and recorded respectively. Statistic analysis was performed by SPSS 13 statistical software, and the consistency of interpretation of the results of different doctors of IDC sonographic features was analyzed by Cohen’s Kappa(K value).Results: The consistency level of the interpretation of the ultrasonographic characteristics of conventional ultrasound of IDC of different doctors according to the 2013 edition of the BI-RADS-US: The consistency of maximum internal diameter, section morphology, Micro Calcium stove, hyperechoic halo, spicule sign and posterior echo attenuation of section was well(K = 0.62, 0.69, 0.71, 0.68, 0.65, 0.62); The margin of the section was not smooth and flat, and the consistency of internal echo(uniform) was medium(K = 0.50, 0.53); The consistency of growth range, posterior echo enhancement and without change of the section were weak(K = 0.30, 0.30, 0.27).The consistency level of interpretation of the ultrasonographic features of IDC contrast-enhanced ultrasound by different doctors according to the observation index of sonographic features of contrast-enhanced ultrasound of breast masses in the eighth chaptor of <Prenatal ultrasound and contrast-enhanced ultrasound guide> that "Guidelines for the clinical application of breast ultrasound angiography" published in 2013 by ultrasound Doctor Association of Chinese Medical Doctor Association: The distribution of contrast agents were not consistent, and the consistency of early enhancement, high enhancement, early extinction and late extinction was well(K = 0.68, 0.75, 0.72, 0.66, 0.71); The consistency of synchronous enhancement, late enhancement, same enhancement, low enhancement and synchronous fading was weak(K = 0.33, 0.20, 0.39, 0.32, 0.29); The consistency of enhancement direction of mass(including: centripetal, centrifugal and diffuse) was weak(K = 0.23, 0.22, 0.17).Conclusion: The research in this group showed that there were differences in the consistency between the results.of IDC conventional ultrasound and CEUS features by different junior doctors(respectively engaged in ultrasound diagnosis in 3 years, 5 years and 8 years). Among them, the consistency of maximum internal diameter, section morphology, Micro Calcium stove, hyperechoic halo, spicule sign and posterior echo attenuation of section in conventional ultrasound observation index and the distribution of contrast agent(uniform), early enhancement, high enhancement, early fade and late fade in ultrasound angiography observation index were well and the effect of physician seniority was relatively weak. The conventional ultrasound observation index that the edge of section was not smooth and flat and the consistency of internal echo(uniform) was medium, therfore the effect of physician seniority was medium; While the conventional ultrasound observation index that the growth direction, posterior echo enhancement, and no change of the section and the consistency of synchronous enhancement, late enhancement, low enhancement, the same enhancement, synchronous fading and mass enhancement direction(centripetal, centrifugal and diffuse) was weak, therefore the relative influence of doctors working experience was big.Thus, different doctors(respectively engaged in ultrasound diagnosis for 3 years, 5 years and 8 years) that higher interpretation consistency of IDC with conventional ultrasound and CEUS features can result in clinical IDC in ultrasonic diagnosis of the differences in interpretation indexes of the results among junior doctors relatively smaller, stability and reliability become relatively higher and recommended as the second part of the observation index of the IDC conventional ultrasound and ultrasound imaging characteristics.Part II: Characteristics of conventional ultrasound and contrast-enhanced ultrasound images of infiltrating ductal carcinoma of the breast and its prognosis correlation analysis of molecular pathological markersObjective: The better interpretation consistency level of IDC conventional ultrasound and contrast-enhanced ultrasound sonographic features was as the observation index according to different doctors in the first part of the study(engaged in ultrasound diagnosis for 3 years, 5 years and 8 years) and the correlation of prognostic markers in molecular pathology was evaluated to provide valuable conventional ultrasound and contrast-enhanced ultrasound imaging features for Preoperative noninvasive prediction of the prognosis of IDC.Materials and methods: The ultrasonic imaging data of 193 cases of IDC patients confirmed by histopathology were selected. The patients in the group of this research had no past treatment history of IDC and all had underwent conventional ultrasound and contrast-enhanced ultrasound before surgery and biopsy. All patients were treated by operation and pathology after surgery was examined by routine pathology and immunohistochemistry(IHC). The expression of ER, PR, HER-2 and Ki-67 of cancer lesions of IDC was recorded by a deputy chief physician in breast pathology diagnosis and all the pathological results of records were complete.The better interpretation consistency level of IDC conventional ultrasound and contrast-enhanced ultrasound sonographic features was as the observation index according to different doctors in the first part of the study(engaged in ultrasound diagnosis for 3 years, 5 years and 8 years) which included: The maximum cross section diameter, shape, micro calcification, peripheral high echo halo, spicule sign and posterior echo attenuation of the section, and the distribution, early enhancement, high enhancement, early regression, late regression of the contrast medium. IDC ultrasonographic features screened in the first part of the study were as the observation index by 2 ultrasound doctors engaged in the diagnosis of breast ultrasound for 5 years and IDC ultrasonography data of 193 patients was observed, analyzed and interpretated and then the results were recorded. When the interpretation was not consistent, it would be reach an agreement by negotiation and as a final interpretation of the results to record.IDC conventional ultrasound and CEUS features and correlation of prognostic markers of molecular pathology were evaluated by Spearman rank correlation analysis. The difference was statistically significant when P<0.05. The observation index that correlated with prognostic markers in molecular pathology [Estrogen receptor(ER), progesterone receptor(PR), human epidermal growth factor(HER-2) and Ki-67] was conducted by Logistic regression analysis and was built as binary logistic regression model to analyze the correlation between them. The difference was statistically significant when P< 0.05.Results: All the 193 cases of the routine pathological examination of tumor specimens incorporated in this study were diagnosed as IDC. Immunohistochemical IDC in 193 cases of pathological specimens were detected in ER positive 137 cases(70.98%), PR positive 123 cases(63.73%), HER-2 positive 115 cases(59.59%), Ki-67 positive 158 cases(81.87%). The correlation between the characteristics of conventional ultrasound and contrast-enhanced ultrasound in IDC and prognostic molecular markers was statistically analyzed by Spearman rank correlation method and the results were that: The correlation between the morphology, micro calcium range, hyperechoic halo, spicule sign and contrast-enhanced sonographic features of the section of IDC and the prognosis of the molecular pathology markers(ER, PR, HER-2 and Ki-67) was not statistically significant(P > 0.05). The correlation between the echo attenuation and ER expression was statistically significant(r = 0.273, P < 0.05) in the sonographic features of conventional ultrasound in IDC; The correlation beween the maximum cross section diameter ≥ 2.0 cm of tumor and the expression of HER-2 and Ki-67 had statistical significance(r = 0.478, 0.258, P < 0.05); The correlation between high enhancement and late subsided and the expression of HER-2 in the characteristics of IDC ultrasound contrast imaging had statistical significance(r = 0.411, r = 0.237, P < 0.05). Logistic regression analysis was performed to analyze the correlation between the above prognosis of molecular pathological markers with statistical significance and the results were that: The dominance ratio of IDC tumor diameter ≥ 2.0 cm with HER-2 and Ki-67 positive expression was high, which indicated the high risk of HER-2 and Ki-67 positive when the tumor diameter ≥ 2.0 cm(OR=10.543, OR=6.206, P < 0.05). The dominance ratio of IDC cancer foci posterior echo attenuation and ER positive expression was high, which indicated that the high risk of ER positive when posterior echo was attenuated(OR=6.026, P < 0.05); The dominance ratio of high enhancement and late regression of IDC contrast enhanced ultrasound and positive expression of HER-2 was high, which indicated high risk of positive expression of HER-2 when high enhancement and late regression occurred(OR=6.034, OR=7.271, P < 0.05).Conclusion: The research results in this group showed that in the characteristics of the image of IDC, the dominance ratio of the maximum cross section diameter of the section ≥ 2.0 cm, ultrasound contrast enhancement, late regression and positive expression of HER-2 was high, that is maximum cross section diameter ≥ 2.0 cm, ultrasound contrast enhancement and late regression ultrasonographic features have potential predictive value of HER-2 positive expression. The dominance ratio of echo attenuation and ER expression was high, that is, the characteristic of echo attenuation ultrasonic image has the potential predictive value of ER positive expression. The dominance ratio of maximum cross section diameter of the section ≥ 2.0 cm and positive expression of Ki-67 was high, that is, the Ultrasonic image features of maximum diameter of the section ≥2.0cm has the potential predicted value of positive expression of Ki-67. The above IDC ultrasound and contrast-enhanced ultrasound sonographic have certain correlation with part of the prognostic markers of molecular pathology, which can provide valuable reference information for noninvasive predicting the prognosis of IDC before operation.