| Part OneThe Prospective Study of Ultrasound Diagnosis System (Conventional Ultrasonography Combined with Ultrasonic Elastography) for Breast CancerObjective To discuss the value of the ultrasound diagnosis system consisted of conventional high-frequency ultrasonography combined with ultrasonic elastography for the diagnosis of breast cancer, and to improve the diagnosis level of breast cancer.Methods The breast mass cases were examined with ultrasound diagnostic system (conventional high-frequency ultrasonography combined with UE).The results were standardly rated according to BI-RADS and the value of ultrasound diagnostic system for the diagnosis of breast cancer was evaluated.502 female cases with 567 breast masses in the First Affiliated Hospital of Guangxi Medical University from May 2010 to December 2011 were enrolled.Chemotherapy, radiotherapy or sex hormone drugs were not taken for all the cases before surgery. All the cases had complete clinical and pathological data.The ultrasonography was performed with GE LOGIQ 9 connected to a wide frequency linear array probe, from 6?15MHZ. The ultrasound diagnostic system included 2DUS,CDFI, PW and UE. Conventional ultrasonography was used to examine the breast and detect whether there were lymph nodes in the bilateral axillary. CDFI was used to observe the blood flow of the lesions. The number,location, size, shape, margin, lesion boundary, echo pattern, posterior acoustic features and microcalcifications and vascularity in lesion were observed.According to BI-RADS, the ultrasonographic manifestations were rated. The mass was regarded as malignant when BI-RADS ? 3. And ultrasonic elastography was used to obtain elasticity scores with the method mentioned by Luo. According to ultrasound diagnostic system, breast masses were rated before surgy. The diagnosis was classified as follows: category: negative, no lesion found, category II :benign finding, category ?: probably benign finding,follow-up after 3-6 months; category?: suspicious abnormality; need to biopsy;category V: highly suggestive of malignancy. Mass was regarded as malignant when ultrasound diagnostic system rating was higher than or equal to IV. The pathological diagnosis was regarded as gold standard, and the performance of ultrasound diagnostic system was evaluated.Results 1. There were 354 benign masses and 213 malignant masses.There were significant differences in ultrasonic characteristics (irregular shape,angualr or microlobulated margin, microcalcifications, decreased posterior echoes and rating ??? blood flow in lesion, resistance index) between malignant cases and benign cases. 2 . The sensitivity, specificity and accuracy of conventional US for the diagnosis of breast cancer were 89.2%, 81.9% and 84.7%, respectively. Those of UE were 85.9%, 89.8% and 88.3%, respectively.And those of conventional US combined with UE were 93.8%, 88.1% and 90.3%, respectively. 3. The accuracy of conventional US combined with UE was significantly higher than conventional US (?2?369.5,P<0.001) and UE (?2=332.2,<0.001).Conclusions The ultrasound diagnosis system (conventional US combined with UE) can improve the accuracy of diagnosing malignant breast lesions and had high value in differentiating benign and malignant masses.Part TwoThe Detection and Analysis of BRCA1 Gene Mutation among Patients with Sporadic Breast Cancer in GuangxiObjective This study was to investigate the prevalence of BRCA1 gene mutation among sporadic breast cancer patients in Guangxi, and to study the relationship between BRCA1 mutation and sporadic breast cancer in Guangxi.Methods 200 female cases (the ultrasonic diagnosis system rating ?4)with sporadic breast cancer in the First Affiliated Hospital of Guangxi Medical University from May 2010 to December 2011 were enrolled. The median age was 47 years old. Chemotherapy, radiotherapy or sex hormone drugs were not taken for all the cases before surgery. All 200 cases had complete clinical and pathological data, and the pathological diagnosis was reviewed by experts.Genomic DNA was isolated from each peripheral blood sample in the experimental group. The primers for BRCA1 were designed with Primer 5 and evaluated with Oligo 7. And all the cases were detected for the entire sequence and splicing sites of BRCA1 genes by PCR-DNA sequencing. 30 healthy women were chosen as control group in the study.Results BRCA1 mutations was not found in 30 healthy women. 17 BRCA1 mutations were found in Exon 10 of BRCA1 among 200 female cases in the experimental group with breast cancer. And the prevalence of BRCA1 mutation was 8.5%. There were two same sense mutations (1624 C>T, 2029 T>C), one nonsense mutation (3452AGAAACA>TT), one frame-shifting mutation (4200delAAAT), and thirteen missense mutations (one case with 1268 C>T, one case with 3971G>A, two cases with 1227 G>A, one case with 2309G>A, four caces with 2238T>C, four cases with 2798T>C). Besides, six single nucleotide polymorphisms (SNPs) were found in BRCA1. They were 2314C/T (NM007300.3, rsl799949), 2543T/C (NM007300.3, rs16940),2844C/T (NM007300.3, rs799917), 3345A/G (NM007300.3, rs16941),3780A/G (NM007300.3, rsl6942), 6308T/G (NM007300.3, rs8176318), four of which led to amino acids encoding change. And all six single nucleotide polymorphisms (SNPs) were mentioned in other studies.Conclusions This study enriches the BRCA1 mutations spectrum of sporadic breast cancer in Guangxi, China and indicated that BRCA1 mutations may play an important role in the development of sporadic breast cancer among patients in Guangxi. This study also indicates that to firstly and mainly detect Exon 10 of BRCA1 can improve efficiency and reduce costs. And this provides a screening model of BRCA1 genetic testing for the future.Part ThreeThe study of the pathological, immunohistochemical and sonographic features of BRCA1 mutation-associated breast cancerObjective This study was to explore the pathological and sonographic characteristics of 17 sporadic breast cancer cases with BRCA1 mutation mentioned in part ?(1.2 Instrument and Method).Methods 183 cases without BRCA1 mutation among 200 breast cancer patients were chosen as control group. The pathological, immunohistochemical and sonographic features of 17 breast cancer patients with BRCA1 mutation were reviewed in comparison with cases without BRCA1 mutation. The pathology and immunohistochemistry were completed by assist of the pathologist. The ultrasonography was the same as Part one.Results 1.The pathological prognostic indicators of 17 BRCA1 gene mutation-associated breast cancer cases showed that triple negative breast carcinoma (TNBC) was 35.3%, and negative expression rate of HER2 was 64.7%. 2.As to sonographic characteristics, there were 10 cases (58.82%) and 164 cases (89.62%) with irregular shape in experimental and control group respectively. There were 10 cases (58.82%) and 112(61.20%) without circumscribed margin (angular or microlobulated) in these two group respectively. There were 7 cases (41.18%) and 84(45.90%) with microcalcifications in these two group respectively. There were 5 cases (29.41%)and 74 cases (40.43%) with decreased posterior echoes in these two group respectively. There were 9 cases (52.94%) and 130 cases (71.04%) with blood,flow rating ??? in these two group respectively. There were 10 cases(58.82%) and 124 cases (67.76%) with RI?0.70 in these two group respectively.There were 11 and 165 cases with BI-RADS rated >3 in experimental and control group respectively, which accounted for 64.70% and 90.16% in each group, and there was significant difference (?2 =9.54, P=0.002). There were 14 cases (82.35%) and 158 cases (86.33%) with elasticity score?4 in elastography in these two group respectively. But there was no significant differences in this index between BRCAl gene mutation carrier and control group (P>0.05).Conclusions This study shows that BRCA1 mutations were closely associated with HER2 negative expression in breast cancer patients. Masses of BRCA1 gene mutation carrier tended to show more benign characteristics in shape, margin, calcifications, posterior acoustic features and the blood flow in the masses according to the conventional ultrasonography.Full text summarizes:1. The ultrasound diagnostic system (conventional ultrasonography combined with UE) can improve the sensitivity and accuracy of diagnosing cancer and has high value for differentiating benign and malignant tumors.2. The BRCA1 gene study of 200 sporadic breast cancer patients enriches BRCA1 gene mutation spectrum of sporadic breast cancer patients in China,especially in Guangxi region and preliminarily explores the clinical genetic testing screening mode for breast cancer.3. BRCA1 mutation-related breast cancer patients have high negative HER2 expression rate. Masses of BRCA1 gene mutation carrier tend to show more benign characteristics in conventional sonographic features. Misdiagnosis might be reduced with the combination of UE. This preliminarily indicates that the prevalence of BRCA1 gene mutations can be forecasted according to the highly negative HER2 expression rate and sonographic features. |
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