The Prognostic Significance of a Combined Determination of Cathepsin D and Estrogen Receptors in Breast Carcinomas with Positive Axillary Lymph Nodes

OBJECTIVE The aim of this study was to investigate the correlation between cathepsin D （Cath-D） and estrogen receptor （ER）expression in breast cancer tissue and to explore the prognostic significance of their combined determination in breast carcinoma patients with positive axillary lymph nodes. METHODS One hundred and thirty-eight cases of breast carcinoma were examined by immunohistochemistry （IHC） and the results relating to patient follow-up analyzed. RESULTS The overall 5-year disease-free survival rate （DFS） was 60.9% （84/138） in the series. The positive rate of Cath-D expression in the tumor cells was 55.07% and the positive ER staining was 51.4%. A definite significant negative correlation was found between the positive rates for Cath-D and ER （r=-0.294, P=0.001） The Cath-D expression for the cases in clinical Stage Ⅱ, ≥10 positive-node and recurrence or distant metastasis, was higher than that those cases in clinical Stage II with fewer node-metastasis and with 5 year DFS （X^2=13.926, P=0.000; X^2=13.070, P=0.001; X^2=10.545, P=0.001）. However, there was no significant difference of Cath-D expression between 2 groups of patients with different ages or among the different histopathologic types of the nonspecific invasive carcinoma. In the combined examination of Cath-D and ER, the cases that were ER （＋） and Cath-D （-） had the highest 5-year DFS compared to other situations. In contrast, the cases that were reversed in expression, ie, ER（-） and Cath-D（＋）, had a lower 5-year DFS. There was a significant difference between the 2 conditions （X2=18.675, P=0.000）. CONCLUSION A combined determination and analysis of Cath-D and ER expression may be more useful to establish a prognosis than the biological characteristics of carcinomas with positive lymph nodes.

Polo-like kinase 1 as a biomarker predicts the prognosis and immunotherapy of breast invasive carcinoma patients

Invasive breast carcinoma(BRCA)is associated with poor prognosis and high risk of mortality.Therefore,it is critical to identify novel biomarkers for the prognostic assessment of BRCA.Methods:The expression data of polo-like kinase 1(PLK1)in BRCA and the corresponding clinical information were extracted from TCGA and GEO databases.PLK1 expression was validated in diverse breast cancer cell lines by quantitative real-time polymerase chain reaction(qRT-PCR)and western blotting.Single sample gene set enrichment analysis(ssGSEA)was performed to evaluate immune infiltration in the BRCA microenvironment,and the random forest(RF)and support vector machine(SVM)algorithms were used to screen for the hub infiltrating cells and calculate the immunophenoscore(IPS).The RF algorithm and COX regression model were applied to calculate survival risk scores based on the PLK1 expression and immune cell infiltration.Finally,a prognostic nomogram was constructed with the risk score and pathological stage,and its clinical potential was evaluated by plotting calibration charts and DCA curves.The application of the nomogram was further validated in an immunotherapy cohort.Results:PLK1 expression was significantly higher in the tumor samples in TCGA-BRCA cohort.Furthermore,PLK1 expression level,age and stage were identified as independent prognostic factors of BRCA.While the IPS was unaffected by PLK1 expression,the TMB and MATH scores were higher in the PLK1-high group,and the TIDE scores were higher for the PLK1-low patients.We also identified 6 immune cell types with high infiltration,along with 11 immune cell types with low infiltration in the PLK1-high tumors.A risk score was devised using PLK1 expression and hub immune cells,which predicted the prognosis of BRCA patients.In addition,a nomogram was constructed based on the risk score and pathological staging,and showed good predictive performance.Conclusions:PLK1 expression and immune cell infiltration can predict post-immunotherapy prognosis of BRCA patients.

Expression of E-cadherin,beta-catenin,cathepsin D,gelatinases and their inhibitors in invasive ductal breast carcinomas

Background E-cadhedn, beta-catenin, cathepsin D, matrix metalloproteinase （MMP）-2, MMP-9, tissue inhibitors of metalloproteinase （TIMP）-1 and TIMP-2 are all invasion-related proteins. The expression patterns of these proteins in invasive ductal breast carcinomas, and their associations with known clinicopathological parameters, tumor recurrence and expressions of estrogen receptor （ER）, progesterone receptor （PR）, PS2 and c-erbB2 were not well studied in Chinese patients, Methods In a set of 94 invasive ductal breast carcinomas, protein expressions of these molecular markers were investigated by immunohistochemistry, and their associations with known clinicopathological parameters, tumor recurrence and expressions of ER, PR, PS2 and c-erbB2 were also examined. In addition, the interrelationship between the expressions of these proteins were studied. Results Preserved membrane E-cadherin expression was associated with late tumor stage and tumor recurrence, whereas the reduced junctional beta-catenin associated with positive lymph node status and c-erbB2 overexpression. Positive staining of cathepsin D in tumor stromal cells displayed a significant association with late tumor stage. High expression of MMP-2 in cancer cells was associated with large tumor size and PR positive expression. TIMP-2 expression was positively associated with tumor recurrence. In addition, inter-relationship between the expressions of these biomarkers was also assessed, Cathepsin D staining in cancer cells was inversely correlated with its staining in stromal cells, and also inversely correlated with MMP-2 staining in tumor stromal cells. MMP-2 expression in stromal cells displayed an inverse correlation with TIMP-2 expression. MMP-9 expression displayed parallel associations with TIMP-1 and TIMP-2 expression. Conclusion Evaluation of E-cadherin, beta-catenin, cathepsin D, MMP-2 and TIMP-2 expression may be of some help in more accurately predictinq the pro qnosis of invasive ductal breast carcinomas.

RAPID DETECTION OF ONCOGENE AMPLIFICATION IN PARAFFIN SECTIONS OF BREAST CARCINOMAS USING QUANTITATIVE DIFFERENTIAL PCR AND FLUORESCENT DNA TECHNOLOGY

Gene amplification is a common mechanism of oncogene activation and contributes to tumor progression. Analysis of such genetic alterations are relevant to the understanding of tumor genetics and could provide prognostic information for the individual patient. Standard analytical approaches using Southern blot and slot blot require a large amount of good

Significance of β-tubulin Expression in Breast Premalignant Lesions and Carcinomas

OBJECTIVE To explore the expression of β-tubulin in premalignant lesions and carcinomas of the breast, and to observe the relationship of its expression with breast cancer pathological features. METHODS The expression of β-tubulin was detected immunohistochemically in 50 specimens of premalignant lesions of the breast （ADH and Peri-PM with ADH）, 50 specimens of breast in situ ductal carcinomas （DCIS）, and 50 specimens of invasive ductal carcinomas （IDC）. Thirty specimens of normal breast tissues served as a control group. RESULTS Immunohistochemical analysis showed that： the differences among the 4 groups （normal breast tissues, breast premalignant lesions, DCIS and IDC, P 〈 0.05） were significant, and there were also statistically significant differences between any 2 groups （P 〈 0.05） except for the β-tubulin positive expression comparing DCIS versus IDC （P 〉 0.05）. In addition, β-tubulin was expressed at a higher level in Peri-PM with ADH compared to ADH （P 〈 0.05）. Following the degree of breast epithelial hyperplasia involved, and its development into carcinoma, the β-tubulin positive expression displayed an elevating tendency. We also found a significant positive relationship of β-tubulin expression with lymph node metastasis （P 〈 0.05）, but no significant correlation with histological grading and nuclear grade. CONCLUSION Centrosome defects may be an early event in the development of breast cancer and they can also promote tumor progression. Studies of aberrations of centrosomal proteins provide a new way to tumorigenesis. explore the mechanism of breast tumorigenesis.

Invasive breast carcinoma with osteoclast-like stromal giant cells:A case report

BACKGROUND Invasive breast carcinoma with osteoclast-like stromal giant cells(OGCs) is an extremely rare morphology of breast carcinomas.To the best of our knowledge,the most recent case report describing this rare pathology was published six years ago.The mechanism controlling the development of this unique histological formation is still unknown.Further,the prognosis of patients with OGC involvement is also controversial.CASE SUMMARY We report the case of a 48-year-old woman,who presented to the outpatient department with a palpable,growing,painless mass in her left breast for about one year.Sonography and mammography revealed a 26.5 mm ×18.8 mm asymmetric,lobular mass with circumscribed margin and the Breast Imaging Reporting and Data System was category 4C.Sono-guided aspiration biopsy revealed invasive ductal carcinoma.The patient underwent breast conserving surgery and was diagnosed with invasive breast carcinoma with OGCs,grade Ⅱ,with intermediate grade of ductal carcinoma in situ(ER:80%,3+,PR:80%,3+,HER-2:negative,Ki 67:30%).Adjuvant chemotherapy and post-operation radiotherapy were initiated thereafter.CONCLUSION As a rare morphology of breast cancer,breast carcinoma with OGC occurs most often in relatively young women,has less lymph node involvement,and its occurrence is not racedependent.

The Immuno-fluorescence Quantity Analysis of α-Tubulin and γ-Tubulin Protein in Precancerous Lesion and Carcinoma of the Breast and Its Significance

OBJECTIVE To investigate the changes and values of the expression of α-tubulin and γ-tubulin in atypical ductal hyperplasia （ADH）, ductal carcinoma in situ （DCIS） and invasive ductal carcinoma （IDC） of the breast. The relationship between centrosome abnormalities and breast tumor development was further discussed. METHODS There were three groups including ADH, DCIS and IDC with 30 cases in each group. They were analyzed by immuno-fiuorescence quantity analysis. The expression levels of α-tubulin and γ-tubulin protein in these tissues were detected by flow cytometry immuno-fiuorescence analysis and compared with the results from normal tissues. Immunohistochemistry was also performed in this research. RESULTS The results showed significant differences of the average of the positive （FITC labeled） cells （P=0.000） among the four groups. The level of the IDC group was the highest, while normal breast tissue showed the lowest level. The results suggested that the expression levels of α-tubulin and γ-tubulin both increased as the grade of cellular proliferation and differentiation increased. The expressions showed significant differences among all the groups, except between the ADH and DCIS. There were no significant differences between α-tubulin and γ-tubulin expression in each group （P〈0.05）, as there was agreement in the immuno-fluorescence and immunohistochemical analysis for protein expression. CONCLUSION There is abnormal expression of centrosome tubulin as an early event in the development of breast tumor. Furthermore these aberrations may play a key role during oncogenesis and promote cellular transformation to malignancy. The immuno-fiuorescence quantitive analysis and immunohistochemistry can complement each other.

Clinical and pathological characteristics of intraductal proliferative lesions and coexist with invasive ductal carcinomas

Objective： The purpose of this study was to study the clinical and pathological characteristics of breast intraductal proliferative lesions （IDPLs） and associated with invasive breast cancer. Methods： We reviewed 327 cases of breast intra- ductal proliferative lesions including 53 cases of usual ductal hyperplasia, 57 cases of atypical ductal hyperplasia, 89 cases of ductal carcinoma in situ, and 128 cases coexist with invasive ductal carcinomas. Cases of pure invasive cancer without intraductal proliferative lesions were excluded. The mult IDPLs biological parameters including the express of ER, PR, HER2, HIF-lo and Ki-67 detected by immunohistochemistry S-P method （n = 327） and the levels of CA153, TSGF, CA125 and CEA both in nipple discharge and serum （n = 179） measured with Electrochemiluminescence method and their relationship were studied, and 30 cases of normal pregnant women were compared with. Results： A single histologic subtype was present in 49.85% （163/327） of the cases, two subtypes in 33.03% （108/327）, and three in 17.13% （56/327）. The most common subtypes present were cribriform （43.12%, 141/327） and solid （38.53%, 126/327）, while the comedo （16.35%, 54/327）, and micropapillary （12.84%, 42/327） subtypes were less common. Comedo and solid were frequently found together for coexpres- sion as were micropapillary and papillary subtypes. However, Comedo subtype was much less likely to be found with papillary, cribriform or micropapillary subtypes. Additionally, comedo subtypes tend to be hormone receptor negative, Her2 positive and high-grade while the cribriform and solid subtype tends to be hormone receptor positive, Her2 negative and low grade. Papil- lary subtype was least likely to be associated with an invasive cancer. Furthermore, the nipple discharge and serum levels of CA153, TSGF, CA125 and CEA in coexist with invasive ductal carcinomas patients were significantly higher than those in the benign breast disease （pure intraductal proliferative lesions） and normal pregnant women （P 〈 0.01）. Additionally, the levels of CA153, TSGF, CA125 and CEA in nipple discharge were significantly higher than in the serum （P 〈 0.01）, and had a positive correlation with the Ki-67, grade, clinical stage, lymph node metastasis and tumor recurrence （P 〈 0.05）, and negative correla- tion with the level of ER and PR （P 〈 0.05）. The sensitivity of the four serum tumor markers in combination was only 69.77%, in contrast, the combined detection both in discharge and serum was 97.67%, and the negative predictive value was 99.03%. The sensitivity of combined detection both in nipple discharge and serum were significantly higher than other detection （P 〈 0.05）. Conclusion： IDPLs often present more than one histologic subtype and the most common subtypes are cribriform and solid, while comedo and micropapillary subtypes are less common. Our results suggest that the levels of CA153, TSGF, CA125 and CEA in nipple discharge were significantly higher than those in the serum, and is associated with HIF-le. The aberration of HIF-la may play a key role during oncogenesis and promote breast cellular transformation into malignancy, a finding useful for further understanding of tumorigenesis. Nipple discharge can be the earliest presenting symptom of breast cancer. The dynamic combined detection of the four tumor markers both in nipple discharge and serum are helpful to the stratification of preoperative patients and benefit to better prewarning markers for monitoring their recurrence and metastasis and clinical staging of tumors in clinic, but cannot increase the sensitivity of judging the patients with early breast cancer.

Expression of HIF-1α in breast cancer and precancerous lesions and the relationship to clinicopathological features

Objective： The aim of this study was to observe the expressions and clinical significance of HIF-1a in breast cancer and precancerous lesions, and analyze the relationship between the expressions and clinicopathological features in breast cancer. Methods： We analyzed the HIF-1a expression in 128 cases of invasive ductal carcinomas, 146 precancerous lesions patients including 89 cases of ductal carcinoma in situ and 57 cases of atypical ductal hyperplasia. 53 cases of usual ductal hyperplasia breast tissues were selected as a control group. The specimens were evaluated for HIF-1a, estrogen receptor （ER） ＆ progesterone receptor （PR）, epidermal growth factor receptor type 2 （HER2/neu） and Ki-67. Immunoreactivity was semi-quantitatively evaluated in at least 1000 cells examined under the microscope at 40 x magnification and recorded as the percentage of positive tumor cells over the total number of cells examined in the same area. The percentage scores were subsequently categorized. The express of HIF-1a and their relationship with multiple biological parameters including ER ＆ PR, HER2/neu and Ki-67, the biomarkers levels of CA153, CA125 TSGF, and CEA in blood serum and nipple discharge, histological grade, region lymph node metastasis, distant metastasis and recurrence on files were also assessed. Results： Compared with usual ductal hyperplasia, the positive expression rate of HIF-1a in atypical ductal hyperplasia, ductal carcinoma in situ and invasive ductal carcinomas group was significantly increased （P 〈 0.01）. The positive rates of HIF-1a in invasive ductal carcinomas were 68.75%, which were significantly higher than that in ductal carcinoma in situ （43.8%）, atypical ductal hyperplasia （31.6%）, usual ductal hyperplasia （9.4%; X2 = 13.44, 22.27, 52.79, respectively, P 〈 0.01）. Statistical analysis showed that difference of abnormal expression rate of HIF-1a between ductal carcinoma in situ and usual ductal hyperplasia （X2 = 18.37, P = 0.00）, atypical ductal hyperplasia and usual ductal hyperplasia （x2 = 8.14, P = 0.00） was significant （P = 0.00）. However, no significant difference in the positive expression rate of HIF-1a was found between atypical ductal hyperplasia and ductal carcinoma in situ tissue （X2 = 2.19, P = 0.14）. There was a significantly difference in the mean HIF-1a frequency between ER ＆ PR positive invasive ductal carcinomas group and negative group, epidermal growth factor receptor type 2 （HER2/neu） positive and negative groups, Ki-67 proliferation index 〈 14% and 〉 14% groups, histological grade （I ＋ II） and grade III invasive ductal carcinomas groups, with lymph node metastasis, distant metastasis and recurrence groups （P 〈 0.05） and without groups （P 〈 0.05）. However, there was not difference in the mean HIF-1a between age （〈 50 years vs 〉 50 years）, tumor diameter （〈 2 cm vs 〉 2 cm; P 〉 0.05）. The nipple discharge and serum levels of CA153, TSGF, CA125 and CEA in invasive ductal carcinomas HIF-1a positive patients were significantly higher than those in the negative patients （P 〈 0.05）. Conclusion： In breast cancer, HIF-1a expressibn was abnormally increased. The aberration of HIF-1a may play a key role during oncogenesis （atypical ductal hyperplasia or ductal carcinoma in situ） and promote breast cellular transformation into malignancy, a finding useful for further understanding of tumorigenesis. The abnormal expression of HIF-1a may be as an early event in the development of breast tumor. The over-expression of HIF-1a might be important biological markers for invasion, metastasis and recurrence of breast cancer.

Expression of Presenilin-2 and Glutathione S Transferase π and Their Clinical Significance in Breast Infiltrating Ductal Carcinoma

To investigate the expressions of presenilin-2 (PS2) and glutathione Stransferase π (GSTπ) and their roles in prognosis and therapy of breast infiltrating ductalcarcinoma. Methods: The paraffin-embedded specimens of 210 patients with breast infiltrating ductalcarcinoma were examined by using LSAB immunohistochemistry for the expression of PS2 and GSTπ.Results: The expression rate of PS2 and GSTπ was 49.5% (104/210) and 48.1% (101/210) respectively.The 5-year and 10-year postoperative survival rates in 4 groups, from high to low, were group 1 (PS2positive expression/GSTπ negative expression), group 2 (PS2 positive expression/GSTπ positiveexpression), group 3 (PS2 negative expression/GSTπ negative expression) and group 4 (PS2 negativeexpression/GSTπ positive expression) in turn. Conclusion: The prognosis of the group 1 was thebest, followed by the group 2, group 3 and group 4 in turn. These results suggested that thereasonable use of endocrinotherapy and chemotherapy for patients with breast infiltrating ductalcarcinoma is necessary.

AG825 increases radiosensitivity of breast cancer cell

Objective:To observe the radiosensitivity effect of AG825 on breast cancer cell line with high expression of ERBB2 in vitro.Methods:MTT and clone formation assay were used to observe the effect of AG825 on proliferation and radiosensitivity of breast cancer line MDA-MB-453.After MDA-MB-453 was exposed to AG825 and radiation,comet assay and Western blotting were applied to detect double strand break and expressions DNA-PKcs protein,respectively.Results:AG825 inhibited proliferation rate and decrease survival fraction of MDA-MB-453.After radiation,compared with control group,expression of DNA-PKcs was lower in group with AG825 presence but double strand break was higher.Conclusion:AG825 could increase radiosensitivity of breast cancer cell line MDA-MB-453,and it may associate with its inhibition of radiation induced expression of DNA-PKcs and double strand break repair.

Expression of Survivin, Mutant p53 and C-erbB-2 in Breast Cancer and Its Clinical Significance

Objective： To investigate the relationship between the expression of survivin and mutant p53, C-erbB-2 proteins in breast cancer to explore the possible molecular mechanisms. Methods： The expression of survivin, mutant p53, and C-erbB-2 was detected in 62 specimens of breast carcinoma by using streptavidin-peroxidase （SP） immunocytochemical assay. Results： Among the 62 cases of breast carcinoma, the positive rate of survivin was 67.7%; 35.5% of the tumors were positive for p53; and 37.1% for C-erbB-2 overexpression. Survivin expression was independent on patient＇s menopausal status, tumor histology, clinical stage, tumor size, lymph node metastasis, and estrogen receptor level. Although survivin expression was not correlated with p53 mutations, the positive expression of survivin was associated with C-erbB-2 overexpression （87.0% vs 56.4%, P〈0.05）. Conclusion： The positive expression of survivin was independent on p53 mutation, but dependent on the overexpression of C-erbB-2. C-erbB-2 might up-regulate the expression of survivin.

Diffusion-tensor imaging as an adjunct to dynamic contrastenhanced MRI for improved accuracy of differential diagnosis between breast ductal carcinoma in situ and invasive breast carcinoma

Objective： To determine the value of diffusion-tensor imaging （DTI） as an adjunct to dynamic contrastenhanced magnetic resonance imaging （DCE-MRI） for improved accuracy of differential diagnosis between breast ductal carcinoma in situ （DCIS） and invasive breast carcinoma （IBC）. Methods： The MRI data of 63 patients pathologically confirmed as breast cancer were analyzed. The conventional MRI analysis metrics included enhancement style, initial enhancement characteristic, maximum slope of increase, time to peak, time signal intensity curve （TIC） pattern, and signal intensity on FS- T2WI. The values of apparent diffusion coefficient （ADC）, directionally-averaged mean diffusivity （D^vg）, exponential attenuation （EA）, fractional anisotropy （FA）, volume ratio （VR） and relative anisotropy （RA） were calculated and compared between DCIS and IBC. Multivariate logistic regression was used to identify independent factors for distinguishing IBC and DCIS. The diagnostic performance of the diagnosis equation was evaluated using the receiver operating characteristic （ROC） curve. The diagnostic efficacies of DCE- MRI, DWI and DTI were compared independently or combined. Results： EA value, lesion enhancement style and TIC pattern were identified as independent factor for differential diagnosis of IBC and DCIS. The combination diagnosis showed higher diagnostic efficacy than a single use of DCE-MRI （P=0.02）, and the area of the curve was improved from 0.84 （95% CI, 0.67-0.99） to 0.94 （95% CI, 0.85-1.00）. Conclusions： Quantitative DTI measurement as an adjunct to DCE-MRI could improve the diagnostic performance of differential diagnosis between DCIS and IBC compared to a single use of DCE-MRI.

Pure Mucinous Carcinoma of the Breast:a Clinicopathologic Analysis with 56 Patients

Objective To assess recent trends and prognostic features in the treatment of pure mucinous carcinoma(PMC) of the breast.Methods Fifty-six patients diagnosed with PMC of the breast in our hospital from December 1982 to June 2008 were included.We evaluated the general information and tumor characteristics of the patients,examined the relationship between these factors and prognosis.Fisher's exact test was applied to analyze tumor characteristics.Results The mean age of the patients was 53.7 years.The majority of the patients presented with early stage disease.Tumor size was found not a significant prognostic factor in this study.Mean follow-up period was 39 months and no breast cancer-related deaths were identified in the patient cohort.Conclusions PMC of the breast has a favorable prognosis.Tumor size does not appear to significantly impact survival.

18β-glycyrrhetinic Acid-induced Apoptosis and Relation with Intracellular Ca^2＋ Release in Human Breast Carcinoma Cells

Objective:To study the effects of 18β-glycyrrhetinic acid (GA) on proliferation inhibition, apop totic induction, and the relationship between GA-induced apoptosis and intracellular Ca2+ concentration in human breast carcinoma (MCF-7) cells. Methods: After MCF-7 cells were treated with GA at the concentrations from 50 μmol/L to 250 μmol/L for 24 h, cell viability of proliferation was assessed by MTT assay. After the cells were treated with 100 μmol/L, 150 μmol/L, and 200 μmol/L GA for 24 h, the rates of cell apoptosis were examined by terminal deoxynucleotide transferase mediated dUTP nick-end-labeling method and flow cytometry with Annexin V/propidium iodide fluorescent stain. After the cells treated with 150 μmol/L GA for 24 h, intracellular Ca2+ concentration was measured by Fure-2 fluorescein load method. Results: After the cells were treated with GA at the concentrations from 100 μmol/L to 250 μmol/L, the rates of proliferative inhibition were increased significantly (P<0.05 and P<0.01) in a dose dependent fashion. IC50 of the proliferation inhibition was 234.33 μmol/L. Treated with 100 μmol/L, 150 μmol/L, and 200 μmol/L, the rates of cell apoptosis were increased significantly (P<0.01). Intracellular Ca2+ concentration after treatment with GA was higher evidently than that of control (P<0.05). Conclusion: 18β-glycyrrhetinic acid has the effects of the proliferation inhibition and the apoptotic induction on MCF-7 cells. The rise of intracellular Ca2+ level may be depended on apoptosis induced by GA in MCF-7 cells.

MicroRNA and histopathological characterization of pure mucinous breast carcinoma

Objective: Pure mucinous breast carcinoma (PMBC) is an uncommon histological type of breast cancer characterized by a large amount of mucin production. MicroRNA (miRNA) is a large class of small noncoding RNA of about 22 nt involved in the regulation of various biological processes. This study aims to identify the miRNA expression profile in PMBC. Methods: MiRNA expression profiles in 11 PMBCs were analyzed by miRNA-microarray and real-time polymerase chain reaction (PCR). Thirty-one PMBCs and 27 invasive ductal carcinoma of no special types (IDC-NSTs) were assessed by immunohistochemistry using antibodies against ER, PR-progesterone receptor, HER2, Ki-67, Bcl-2, p53, PCNA, and CK5 and 6. Results: We analyzed the miRNA expression in 11 PMBCs and corresponding normal tissues using miRNA-microarray and real-time PCR, and found that miR-143 and miR-224-5p were significantly downregulated in mucinous carcinoma tissue. Compared with IDC-NSTs, PMBC showed a significantly higher ER positive rate, lower HER-2 positive rate, and lower cell proliferation rates. Conclusions: To our knowledge, this is the first study to demonstrate the miRNA expression profile of PMBC, and our findings may lead to further understanding of this type of breast cancer.

Expression and Clinical Significance of Vascular Endothelial Growth Factor in Benign and Malignant Tissues of Breast

Objective： To detect the expression of vascular endothelial growth factor （VEGF） and microvessel density （MVD） count in breast benign affection, breast atypical hyperplasia and breast carcinoma in situ, and to clarify the relationship between VEGF expression, MVD and the clinicopathological features of these diseases. Methods： The expression of VEGF and MVD count in 115 cases breast benign diseases （including 40 breast fibroid tumor, 40 breast cystic hyperplasia and 35 intraductal papilloma, 19 breast atypical hyperplasias and 32 breast carcinomas in situ were examined by immunohistochemistry staining （SP-method）. Results： The positive rate of VEGF in breast benign diseases, breast atypical hyperplasia and breast carcinoma in situ were 21.74%（25/115）, 31.58.% （6/19）and 53.13%（17/32） respectively. It was the lowest in breast benign affection group, and was the highest breast carcinoma in situ group. The expression of VEGF increased gradually in the three groups （P〈0.05）. The MVD count of the three groups were 14.41 ± 2.59, 18.89± 4.47 and 21.13 ± 4.12 respectively, It was the lowest in breast benign affection group, and was the highest breast carcinoma in situ group. The MVD count of the three groups increased gradually （P〈0.05）. In VEGF positive group, MVD count was 19.41 ±4.78; In VEGF negative group, MVD count was 14.91±3.15. The MVD count was higher in VEGF positive group than that in VEGF negative group （P〈0.05）. Conclusion： The results of this study suggested that VEGF could promote microvessel growth in breast tumors. The occurrence and progression of breast cancer might be related with the expression of VEGF.

Breast-conserving therapy and modified radical mastectomy for primary breast carcinoma:a matched comparative study

Background- To compare two types of therapy for primary breast carcinoma, breast-conserving therapy （BCT） and modified radical mastectomy （MRM）, in a matched cohort study. Methods： A series of 1,746 patients with primary breast cancer treated with BCT or MRM in a single Chinese institute between January 2000 and February 2009 were analyzed retrospectively to compare their outcomes with respect to the incidence of local recurrence （LR）, distant metastasis, and survival. The patients were matched with regard to age at diagnosis, spreading to axillary lymph nodes, hormone receptor status, the use of neoadjuvant chemotherapy and maximal tumor diameter. The match ratio was 1：1, and each arm included 873 patients. Results： The median follow-up period was 71 months. The 6-year disease-free survival （DFS） and 6-year distant disease-free survival （DDFS） rates differed significantly between two groups. The 6-year local recurrence-free survival （LRFS） rates were 98.2% [95% confidence interval （CI）： 0.973-0.989] in the BCT group and 98.7% （95% CI： 0.980-0.994） in the MRM group （P=0.182）, respectively. DFS rates in BCT and MRM groups were 91.3% （95% CI： 0.894-0.932） and 86.3% （95% CI： 0.840-0.886） （P〈0.001）, respectively, whereas the DDFS rates in BCT and MRM groups were 93.6% （95% CI： 0.922-0.950） and 87.7% （95% CI： 0.854-0.900） （P〈0.001）, respectively. Conclusions： BCT in eligible patients is as effective as MRM with respect to local tumor control, DFS and DDFS, and may result in a better outcome than MRM in Chinese primary breast cancer patients.

Metastatic breast cancer to the gastrointestinal tract:A case series and review of the literature

Metastatic breast cancer involving the hepatobiliary tract or ascites secondary to peritoneal carcinomatosis has been well described. Luminal gastrointestinal tract involvement is less common and recognition of the range of possible presentations is important for early and accurate diagnosis and treatment. We report 6 patients with a variety of presentations of metastatic breast cancer of the luminal gastrointestinal tract. These include oropharyngeal and esophageal involvement presenting as dysphagia with one case of pseudoachalasia, a linitis plastica-like picture with gastric narrowing and thickened folds, small bowel obstruction and multiple strictures mimicking Crohn’s disease, and a colonic neoplasm presenting with obstruction. Lobular carcinoma, representing only 10% of breast cancers is more likely to metastasize to the gastrointestinal tract. These patients presented with gastrointestinal manifestations after an average of 9.5 years and as long as 20 years from initial diagnosis of breast cancer. Given the increased survival of breast cancer patients with current therapeutic regimes, more unusual presentations of metastatic disease, including involvement of the gastrointestinal tract can be anticipated.

Establishment of VX2 breast carcinoma model in rabbit by injecting tumor mass suspension

Objective: To establish a stable model of VX2 breast carcinoma in rabbit and select the optimal way. Methods: Thirty female New Zealand rabbits were randomly divided into 3 groups with 10 in each. Tumor cell suspensions or tumor mass suspensions were injected into breast tissues of rabbits of group A and B, respectively. Tumor blocks were surgically implanted in rabbit breasts of group C. Tumor formation rate, tumor growth rate, and tumor-bearing survival time was compared, and the histological feature of tumor was observed. Results: Models were established conveniently and successfully in rabbits received injection of tumor mass suspensions. Tumor proliferated rapidly with the biological feature of squamous cell carcinoma. Conclusion: VX2 breast carcinoma model in rabbit was established successfully. Intramammary injection of tumor mass suspension is the best method.