The Value Of Tumor Peripheral Nourishing Vessels In The Diagnosis Of Breast Cancer And Its Correlation With Tumor Markers

BackgroundThe risk of female breast cancer presents a globalizing trend,while the prevalence of female breast cancer in China has its own characteristics,that is,it shows significant ruralization and younger in age,as a result,the mortality rate of breast cancer increases,this not only has a serious impact on the families of the patients,but also imposes a heavy burden on society.Therefore,medical workers regard the prevention and treatment of breast cancer as the focus and hotspot of extensive attention.The secretion of vascular endothelial growth factor in mammary tumors promotes a large number of angiogenesis,leading to differences in the distribution of blood vessels in the tumor marginal zone and in the central region of the tumor.The current study considers that the heterogeneity of tumor blood vessels is determined by the type and microenvironment of the tumor,the active regulation of tumor-associated stromal cells plays a key role in the microenvironment.The inconsistency of this regulation in spatial and temporal expression leads to tumor vessels,there is a significant difference in the generation and angiogenesis under physiological conditions.Previous studies have confirmed that the blood perfusion intensity in the peripheral area of malignant breast tumors is significantly greater than that in the central area of tumor,and the blood vessels in the surrounding area are more densely distributed.The growth rate of the breast cancer is fast,the internal blood flow is insufficient,the necrotic area leads to the sparsity of the internal vessels,and the blood flow is less than the surrounding area of the tumor.Previous research and tumor therapy are more focused on the internal vessels of the tumor,often ignoring the peripheral nourishing artery.Malignant breast tumors thrive,there are nourishing blood vessels in the periphery of the tumor that distort the radial or encircling tumors,this nourishing artery determines the rate of growth and invasiveness of this tumor.In order to ensure the rapid growth of breast cancer,the diameter of the nutrient arteries around the tumor is often irregular thickening,so as to store enough blood flow to multiple branches of the tumor,these characteristics have become the basic conditions for easy detection by ultrasound.The supply of blood vessels in breast malignancies is a key factor in tumor expansion and invasion.With the increasing resolution of high-frequency ultrasound,the ability to detect malignant nodules with an intra-mammary diameter of less than 10 mm is becoming easily,these small breast nodules sonographic performance is not very specific.In addition,the malignant tumors of the breast grow rapidly,with necrotic lesions inside.The appearance of these conditions makes the nourishing blood vessels around the breast tumors useful for the differentiation of benign from malignant tumors.At present,there are few reports about the relationship between the flow spectrum of nutrient arteries around the tumor and the benign or malignant breast tumors.With the advancement of science and technology,molecular biology has been rapidly developed,and medical workers have gradually realized that in the process of the formation and development of breast cancer,the molecular markers of cancer have significant effects on the invasion and growth of cancer.An important marker of breast cancer with progesterone receptor(PR),vascular endothelial growth factor(VEGF),estrogen receptor(ER),human epidermal growth factor receptor 2(HER2,C-erbB-2 is neu of HER2)and Ki-67 subtypes,these molecular markers have important reference value to the clinician in the assessment of individual breast cancer diagnosis,clinical treatment options.Furthermore,at present,for some malignancies,a program for performing neoadjuvant chemoradiation followed by surgery is proposed clinically,these above-mentioned tumor markers are direct evidence of whether the curative effect is satisfactory or not.However,it is necessary to judge the expression of tumor markers by observing tissue specimens through pathological and epidemiological techniques,these tissue specimens must be obtained by biopsy or surgical resection.Therefore,how to use non-invasive imaging methods to obtain the relationship between the morphological changes of tumors and the expression levels of molecular markers related to the prognosis of breast cancer,so as to indirectly reflect the biological behavior of tumors and provide basis for further clinical treatment,the focus and hotspot of breast cancer imaging research at home and abroad at present.Previous studies have confirmed that the internal vessels of tumor are closely related to these molecular markers,but few literatures have reported the relationship between tumor peripheral vascular and tumor markers.Therefore,if we can find out the difference of breast cancer and fibroadenoma tumor surrounding trophoblast artery,not only have a vaule for differentiating benign and malignant,but also have a vaule for small cancers with no signs of blood flow and no significant signs of malignancy in the breast.And the diagnosis of necrosis and liquefaction of cancer foci has reference value.If we can find the correlation between the tumor surrounding blood vessels and tumor pathological markers,we can use ultrasound to observe the nourishing artery around the breast cancer to observe the change of neoadjuvant radiotherapy and chemotherapy before and after using the non-invasive.This imaging method can indirectly reflect the biological behavior of the tumor and provide a basis for further clinical treatment.It is based on the above considerations,that a study has been conducted on the nourishment of blood vessels around breast tumors.PART I The diagnostic value of the peripheral trophoblastic artery and the contrast-enhanced ultrasound of peripheral region in the differential of benign and malignant breast tumorsObjective To explore the feasibility and application value of the peripheral nutrient artery in discriminating breast benign and malignant solid tumors,and to investigate the value of contrast-enhanced ultrasonography in the peripheral region to distinguish between benign and malignant tumors of breast.Methods The peak systolic velocity(PSV)and resistive index(RI)of peripheral nutrient artery of 220 breast masses were detected by color doppler ultrasonography.All the cases were confirmed by operation and pathology.Intraclass correlation coefficient(ICC)was applied to evaluate reproducibility of the measurement of peripheral nutrient arteries.ROC curve was used to determine the critical value of diagnosis.Contrast-enhanced ultrasonography was performed on 46 of the breast lesions.Contrast-enhanced contrast intensity and angiographic parameters were compared between the benign and malignant breast lesions.Results Among the 220 breast tumors,there were 97 breast cancer lesions with a diameter of 7-52 mm,average(23.7±10.8)mm,and 123 benign lesions with a tumor diameter of 9-39 mm and an average of(19.5±4.8)mm.The reliability of three measurements of PSV and RI in the spectrum of nourishing arteries surrounding a solid mass of breast was greater than 0.75.The values of PSV and RI in the spectrum of nourishing artery around breast cancer were higher than those in benign breast tumors(P<0.05).Around the breast cancer,the radial arteries of the nutrient arteries were mostly radiating,the peripheral arteries of the benign breast tumors were mostly circular,there was differences in the way of nutrient arteries between the breast cancer and the fibroadenoma(P<0.05).The cut-off point of PSV and RI value in peripheral nutrient arteryof breast cancer was determined as 16.5 cm/s and 0.715,the corresponding diagnostic sensitivity,specificity,negative predictive value and positive predictive value were 86.60%,56.60%,84.15%,61.31%and 91.75%,79.51%,92.38%and 78.07%respectively.There were 29 breast carcinomas and 17 breast fibroadenomas among the 46 breast lesions.Contrast-enhanced ultrasonography of 46 breast lesions showed that most of the peripheral regions of breast cancer were highly enhanced,while the peripheral regions of fibroadenoma were mostly low or equal(P<0.05).Compared with breast fibroadenoma,radial perfusion was common in the peripheral area of breast cancer(P<0.05).In the comparison of angiographic parameters,the peak time of the imaging parameters in the peripheral area of breast cancer was faster than that of fibroadenoma,and the area under the curve was larger than that of fibroadenoma(P<0.001).Conclusion It was stable for the nourishing artery appling in breast ultrasonic,which had the unique advantage of non-invasive and convenient.It could be used as a supplementary method on the basis of two-dimensional ultrasound diagnosis and differential diagnosis of benign and malignant breast tumors.The contrast-enhanced sonography had certain clinical value in differentiating between benign and malignant lesions of the breast.It also further confirmed that the distribution of blood vessels around the benign and malignant breast tumors was different.PART ? The value of tumor related factors C-erbB-2,Ki-67and VEGF in the diagnosis of invasive ductal carcinoma of the breastObjective To tinvestigate the relationship between the expression of C-erbB-2,Ki-67 and VEGF in tumor markers and the axillary lymph node metastasis of infiltrating ductal carcinoma(IDC)and its influence on histopathologic grading,so as to provide a theoretical basis for clinical prognosis evaluation.Methods The data of 122 cases of female breast invasive ductal carcinoma were retrospectively analyzed.HE staining and immunohistochemical techniques were used to study 122 lesions of 122 female patients who underwent breast cancer resection in our hospital.The relationship between the expression of tumor related factors C-erbB-2,Ki-67,ER and VEGF on the clinical histological grade and axillary lymph node metastasis of invasive ductal carcinoma of the breast was analyzed.Results The age of 122 cases of breast IDC patients was 29?80 years of age,the average(52.6 + 11.3)years.The diameter of 122 lesions was IDC 7?68mm,the average(24 + 11.6)mm.The lesions larger than 20mm in diameter were 64,and 58 cases were<20mm.The positive expression of C-erbB-2 was 39.3%(48/122),and the negative expression was 60.7%(74/122).75 patients had histological grade greater than or equal to grade II,and 47 grades less than grade ?.61 cases developed axillary lymph nodes,the positive expression of ER and PR were 58 and 54 lesions,respectively.The positive expression of Ki-67 cases were 97,accounting for 79.5%(97/122),Ki-67 negative expression in 25 cases,accounting for 20.5%of the total(25/122).The positive expression of VEGF was 63.1%(77/122),negative expression of VEGF accounted for 36.9%of the total(45/122).The majority of patients with positive expression of C-erbB-2 and Ki-67 were more than or equal to grade II histological grade,and were more likely to have axillary lymph node metastasis(P<0.05).The majority of C-erbB-2 positive expression showed positive ER and PR(P<0.05).When the expression of Ki-67 and VEGF were positive,the tumor diameters were mostly greater than or equal to 20 mm(P<0.005).When the VEGF expression of breast IDC was positive,the majority of patients were prone to axillary lymph node metastasis(P<0.05).Conclusion When the tumor markers C-erbB-2 and Ki-67 were positive in the breast IDC,the histological grades of the lesions were mostly greater than or equal to grade II,and most cases of axillary lymph node metastasis occurred.When C-erbB-2 positive expression was observed,most of the estrogen receptors ER and PR were positively expressed.Ki-67 and VEGF were positively expressed,the majority of tumors grew rapidly,and the majority of tumors had a diameter greater than or equal to 20 mm.Therefore,the positive expression of tumor markers C-erbB-2,Ki-67,VEGF affects the histological grade and distant metastasis of breast IDC.PART ?Correlation between peripheral nutrient arteryand expression of C-erbB-2 in breast invasive ductal carcinoma.Objective To evaluate the relation between peripheral nutrient artery and expression of C-erbB-2 in breast invasive ductal carcinoma(IDC).Methods The peak systolic velocity(PSV)and resistive index(RI)ofperipheral nutrient artery of tumor in 122 cases with breast IDC and 138 cases with fibroadenoma which proved by operation and pathology were analyzed retrospectively.The C-erbB-2 were measured by immunohistochemical test,according to the results of immunohistochemical examination,the masses were divided into negative group(-),weakly positive group(+),positive group(++)and strong positive group(+++).The relationship between the classification of C-erbB-2 expression and the two factors of peripheral nutrient artery inbreast tumor mass were analysed.Results ThePSV of trophoblastic artery in IDC group was(20.99 ±8.14)cm/s,RI 0.66±0.07,the PSV of trophoblastic arteryinfibroadenoma group was(15.56±3.68)cm/s,RI 0.66±0.07,there was significant statistically in peripheral nutrient artery of tumor between the breast IDC and fibroadenoma(P<0.05).the RI and PSV of the peripheral nutrient artery inIDC were correlated to the classification of C-erbB-2 expression(P<0.O01,r values were 0.323 and 0.360 respectively),there was no correlation between the RI and PSV ofperipheral nutrient artery in fibroadenoma and the classification of C-erbB-2 expression(r values were 0.001).Conclusions The spectrum form of peripheral nutrient artery in IDC is high speed and high resistance.The RI and PSV of the peripheral nutrient artery in IDC are correlated to the classification of C-erbB-2 expression.PART IV The relation of the expression antigen Ki-67 and the diameter to the peripheral nutrient artery of tumor in breast infiltrative ductal carcinoma.Objective To evaluate the relation of appearance of Ki-67 and the diameter to the peripheral nutrient artery of tumor in breast infiltrative ductal carcinoma(IDC).Methods The tumor diameter and peripheral trophic artery peak flow velocity(PSV)and resistance index(RI)of 137 cases of breast IDC were retrospective analysised,all cases were confirmed by surgery and pathology,tumor specimens Ki-67 expression of postoperative immunohistochemistry was measured and Ki-67 was divided into 4 grades(strong positive,positive,weak positive,and negative)based on the number of cell stainings shown in the immunohistochemical plot,using "++++","++","+","-",respectively.The relationship between the peripheral nourishing artery and diameter of 137 cases IDC tumor and expression level of Ki-67 were analyzed.Results The diameter of 137 cases breast IDC was from 7mm to 68mm,the average(24 + 11.6)mm,Ki-67 positive expression rate was 81%(111/137).The tumor surrounding trophoblastic artery RI and tumor diameter in the Ki-67 "-" group and the"+"group and the "+" and "+++" group showed different,the difference was statistically significant(F=3.52 and 2.76,P=0.017 and 0.045).The classification of Ki-67 expression was positively correlated with the diameter of the nodules(P<0.05),there were correlated between the PSV and RI of the peripheral vessels in the tumor and the classification of Ki-67 expression(P<0.05).The PSV and RI of the peripheral vessels of the 137 breast IDC tumors were positively correlated with the diameter of the tumor(P<0.05).Conclusions The classification expression of Ki-67 and the diameter of mass in the breast are related to the peripheral nutrient artery of tumor in breast infiltrative ductal carcinoma.