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.

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.

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.

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.

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.

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.

Effect of amlodipine on apoptosis of human breast carcinoma MDA-MB-231 cells

Objective： To elucidate the effects of amlodipine on the proliferation and apoptosis of human breast carcinoma MDA-MB-231 cells. Methods： Light microscopy was used to determine the effects of amlodipine on cell morphology; Flow cytometry was used to quantitate cells undergoing apoptosis; the expression of a cell cycle-related protein, proliferating cell nuclear antigen （PCNA） and an antiapoptosis protein, Bcl-2 were assessed by immunocytochemistry. Results： Amlodipine concentration of 8.25umol/L （1/2 of ICs0） affected the morphology, decreased the expression of PCNA and Bcl-2 and induced apoptosis of human breast carcinoma MDA-MB-231 cells. Conclusion： The effect of amlodipine on the antiproliferation of human breast carcinoma MDA-MB-231 cells is related to inducement of apoptosis, and the decrease of the expression of Bcl-2 and PCNA may be the possible mechanism for proliferation inhibitory and inducement of apoptosis.

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.

Identification of TM9SF2 as a Candidate of the Cell Surface Marker Common to Breast Carcinoma Cells

OBJECTIVE We aimed identification of cell surface molecules, which might serve as diagnostic biomarkers or useful targets for therapies, in breast cancer. METHODS We developed unique DNA microarray coupled with spherical self-organizing map （sSOM） analysis to characterize cells and tissues by the cell surface markers. In the microarray 1,797 probes for human genes coding membrane bound proteins were spotted. With this microarray the gene expression profiles of eight breast carcinoma cell lines were compared to identify the genes that were commonly expressed in breast carcinomas but not in normal cells. RESULTS The gene expression profiles of sSOM from the eight breast carcinoma cell lines were successfully distinguished from that of normal breast tissue derived cells suggesting the presence of genes of interest, sSOMon the data extensively filtered revealed several candidate genes, of which expression was significant in carcinoma cells but low in normal cells. Finally, TM9SF2 was nominated through validations of PCR procedures together with CD24 and ErbB3, which are known breast carcinoma markers. TMgSF2 expression was further confirmed by immunological staining. Interestingly, TMgSF2 was found to be expressed in all the cell lines evaluated while CD24 and ErbB3 were not in all of the carcinoma cells, supporting their relationship in sSOM. Although physiological significance of TMgSF2 is unknown yet, siRNA treatment significantly inhibited the growth of MDA- MB-231 cells. CONCLUSION We propose TM9SF2 as a novel and useful diagnostic marker as well as a potential molecular target specific to breast carcinoma cells covering wide range of breast cancer.

EXPRESSION AND SIGNIFICANCE OF ERK PROTEIN IN HUMAN BREAST CARCINOMA

Objective: To investigate the expression of ERK and p-ERK protein in human breast cancer and their corresponding tissue, to assess the significance of ERK signal pathway in tumorigenesis and progression of breast carcinoma. Methods: 40 breast cancer cases were used in S-P immunohistochemistry technique and Western Blot study. Results: The expression of ERK1, ERK2, and p- ERK protein levels increased remarkably in breast cancer tissues in comparison to normal tissues (P<0.01). The expression was upregulated by 1.32-, 1.53-and 4.27-fold, respectively. The overexpressions of ERK1, ERK2, and p- ERK proteins were obviously correlated with clinical stage of breast cancer. Protein levels of ERK and p-ERK were higher in stage III patients than in stage I and stage II patients (P<0.05). These proteins were strongly related with axillary lymph node metastasis of breast cancer, but not correlated with histopathological type and status of ER and PR of breast cancer. Expression of ERK1, and ERK2, protein showed a positive linear correlation. Conclusion: ERK signal transduction pathway is a key factor during human breast tumorigenesis and breast cancer progression.

CLINICAL SIGNIFICANCE OF P-GLYCOPROTEIN EXPRESSION IN METASTATIC BREAST CARCINOMA

Objectives: To evaluate the expression of P-glycoprotein (P-gp) and it's effect on chemotherapy response in metastatic breast carcinoma. Methods: 46 postoperative patients with metastatic breast carcinoma were enrolled. P-gp expression was detected by SABC immunohistochemical method. These patients were treated with combined chemotherapy of cyclophosphamide, pirarubicin and 5-fluorouracil for at least two cycles. The relationship between P-gp expression and chemotherapeutic response was analyzed. Results: The positive rate of P-gp expression was 56.5%, the P-gp expression in the patients with lung or liver metastasis was higher than that in patients with skin or lymph node metastasis (P=0.049). The overall response rate was 58.1% in 43 patients; the response rate (89.5%) of the P-gp negative group was higher than that (30.0%) of the P-gp positive group (P<0.01). The response rate (87.5%) in the patients with skin or lymph node metastasis was higher than that (40.7%) in the patients with lung or liver metastasis (P<0.05). In the postoperative patients who had received CAF or CMF regimen adjuvant chemotherapy previously, the response rate of metastatic diseases to chemotherapy had no significant difference (71.4% and 37.5%, respectively) (P=0.052). Conclusion: Patients with metastatic breast carcinoma had higher P-gp expression and these patients should be treated with non-MDR drugs chemotherapy.

CORRELATION BETWEEN LAMININ AND CATHEPSIN D EXPRESSIONS IN BREAST CARCINOMA

Objective： Laminin is a major glycoprotein component of basement membrance which is an important barrier to tumor cells which must be breeched before metastatic spread can occur. Proteolytic enzymes play an important role in mediating the passage of cancer cells through the basement membrane （BM） and extracellular matrix. We compared the patterns of laminin and cathepsin D （CD） expressions in a range of benign and malignant breast lesions to better understand the process of tumor progression. Methods： One hundred and sixty-two cases of breast samples comprising 18 fibroadeomas, 22 cases of fibrocystic disease, 96 cases of invasive ductal carcinoma and 26 carcinomas with intraductal components were evaluated for laminin and cathepsin D expressions by immunohistocbemical staining. Results： The prevalence of CD positivity in both neoplastic and stromal cell components were significantly higher in higher histological grade tumors compared to lower grades （P〈0.001）. Various severity of BM disruption correlated with histological grade of the carcinomas （P〈0.001）. There was a negative correlation between the laminin expression and CD presence. Conclusion： In the process of cancer cell invasion and metastasis, the basement membrane is disrupted by proteinase secreted by cancer cells, especially by stroma cells of cancer.

RELATIONSHIP BETWEEN EXPRESSIONS OF P38 PROTEIN IN HUMAN BREAST CARCINOMA AND LYMPH NODES METASTASIS

Objective： To detect the change of p38 protein expression and investigate the relationship of p38 and lymph nodes metastasis in human breast carcinomas. Methods： Sixty breast cancer cases were checked by S-P immunohistochemistry technique and 30 breast cancer cases were examined by Western Blot. Results： Immunohistochemical results showed that p38 protein was observed in breast cancer and normal cytoplasm. P-p38 was positive in nucleus in breast cancer. P38 protein expressed positively in 29 out of 38 patients who had lymph nodes metastasis （positive rate 76.3%） and in 9 out of 22 patients who had no lymph nodes metastasis （positive rate 40.9%）. There was a significant difference between these two groups （P〈0.01）. The positive rate of p-p38 in patients who had lymph nodes metastasis was 68.4%, and the positive rate in patients who had no metastasis was 36.4%, and there was a significant difference between these two groups （P〈0.05）. The result of western blot showed that the protein contents of p38 and p-p38 in patients with metastasis was higher than those in patients without metastasis （P〈0.05）. P38 and p-p38 protein expressions had relation with clinical pathological grades in breast cancer, higher in grade Ⅲ than in grade Ⅰ, Ⅱ （P〈0.05）, while had no relation with patients＇ age and tumor size （P〉0.05）. Conclusion： p38 and p-p38 protein expressions had relationship with lymph nodes metastasis and the levels of p38 and p-p38 protein expression in groups with lymph nodes metastasis were higher than in groups without lymph nodes metastasis. P38 and p-p38 protein expressions had relationship with clinical grades and had no relationship with patients＇ age and tumor size.

EXPRESSION AND CLINICAL SIGNIFICANCE OF p73A IN BREAST CARCINOMA TISSUES

Objective: To study the expression and clinical significance of p73α in breast carcinomas. Methods: The expression of p73α was detected by immunohistochemistry in 41 breast carcinoma tissues, 13 benign breast tumor tissues and 8 normal tissues and 8 normal breast tissues, respectively. Results: The positive expression of p73α was found in 20/41 (48.8%) of breast carcinoma tissues, 1/13 (7.7%) of benign breast tumor tissues. The positive expression rate of p73α in breast carcinoma tissues was significant1y higher than that in benign breast tumor tissues and normal breast tissues (P<0.05). The expression intensity of p73α increased significantly in breast carcinoma tissues compared with benign breast tumor tissues and normal breast tissues (P<0.05). Significant association of the expression of p73α with lymph node metastases and TNM stages of the carcinoma was found (P<0.05). The expression of p73α displayed a positive correlation with p53 (P<0.05). Conclusion: These results suggest that there is an up-regulation of p73α expression in breast carcinoma tissues, which may be implicated in the tumorigenesis of breast carcinoma as a molecular alteration.

EXPRESSION OF ONCOGENE AND ANTI-ONCOGENE IN MALE BREAST CARCINOMA

Expression of oncogene and anti-oncogene products in 12 cases of male breast carcinoma was studied.Positive staining was seen in 6 cases for c-myc,6 cases for EGFR.4 cases for c-erbB-2 cases for N-ras,5 cases for Rb and 3 cases for P53.One case was positive and 4 cases were negative for all above mentioned oncogene and antioncogene products.In addition,Cathepsin D(Cath-D),ER.PR,AR.PCNA and AgNOR were also assayed.In all the cases showed c-erbB-2 or P53 positive were Cath-D positive.The significance of expression of c-erbB-2,c-myc,Cath-D,ER and PR in male breast carcinoma was emphatically discussed.

Migration of the localization wire to the back in patient with nonpalpable breast carcinoma: A case report

BACKGROUND Due to the increasing number of diagnosed nonpalpable breast cancer cases,wire localization has been commonly performed for surgical guidance to remove nonpalpable breast lesions.This report presents a rare case of localized wire migration to a subcutaneous lesion of the upper back in a breast cancer patient undergoing breast-conserving surgery.CASE SUMMARY A 48-year-old female was scheduled for breast-conserving surgery for left breast cancer.Ultrasonography guided wire localization was performed intraoperatively by surgeon to localize the nonpalpable breast cancer.After axilla sentinel lymph node biopsy,we realized that the wire was not visualized.The wire was not found in the operation field,including the breast and axilla.Breast-conserving surgery was performed after wire re-localization.Intraoperative chest posteroanterior view revealed that the wire was located on the level of midaxillary line.Two days after the operation,a serial simple X-ray revealed that the wire was located on the subcutaneous lesion of the back.The wire tip was palpable under the skin of the upper back,and the wire was removed under local anesthesia.CONCLUSION Hooked wire misplacement can lead to fatal complications.Surgeons must consider the possibility of wire migration during breast cancer surgery.

Retinoic acid affects basic cellular processes and SOX2 and SOX18 expression in breast carcinoma cells

Genetic and molecular heterogeneity,together with intrinsic and acquired resistance to therapy,represent the major obstacles to the successful treatment of different types of breast carcinoma.Increasing evidence demonstrates that SOX transcription factors in breast carcinomas could act both as oncogenes and tumor suppressors and have been associated with tumor stage and grade,poor prognosis,and therapy resistance.Both SOX2 and SOX18 overexpression has been correlated with poor prognosis in breast carcinomas,and these genes are recognized as potential antitumor targets.Our aim was to evaluate the effect of retinoic acid(RA),a well-known cyto-differentiating agent,on breast carcinoma cells in vitro and to investigate the potential of RA treatment to modify the expression of SOX2 and SOX18 genes.By applying various experimental approaches,we evaluated the effect of RA on basic cellular processes in SK-BR-3 and MCF7 breast carcinoma cell lines.We have shown that RA inhibits cell growth,reduces the number of Ki-67 positive cells,and causes cell-cycle arrest.RA effect was more prominent in SK-BR-3 cell line that lacks SOX2 expression,including a higher decrease in cell viability,reduction in colony formation,and significant remodeling of cellular structure.We have shown that RA treatment led to the downregulation of SOX2 expression in MCF7 cells and to the reduction of SOX18 expression in both cell lines.By functional analysis,we showed that the anti-proliferative effect of RA in both cell lines was not based on the activity of stemness marker SOX2,pointing to a SOX2-independent mechanism of action.The ability of RA to reduce SOX2/SOX18 expression raises the possibility that these genes can be used as biomarkers to distinguish RA-responders from non-responders.Together,our study shows that the response of breast carcinoma cell lines to RA treatment may vary,highlighting that the development of RA-based therapy should consider differences in breast carcinoma subtypes.

Infiltrating ductal breast carcinoma with monoclonal gammopathy of undetermined significance:A case report

BACKGROUND Infiltrating ductal breast carcinoma with monoclonal gammopathy of undetermined significance(MGUS)is rare and easily misdiagnosed.Most patients are first diagnosed with MGUS.We report a rare case of MGUS secondary to infiltrating ductal breast carcinoma.We also review the literature to analyze the clinical characteristics and diagnostic methods.CASE SUMMARY A 51-year-old woman underwent modified radical mastectomy for infiltrating ductal carcinoma of the right breast and was then treated with radiation and chemotherapy.A decreased platelet count was found on routine blood examination,and MGUS was subsequently diagnosed.This is the first report of the occurrence of MGUS after breast cancer surgery.CONCLUSION Vigilance is required to distinguish this rare comorbidity from breast plasmacytoma.

Relationship between p38MAPK activity and apoptosis during the drug resistance of breast carcinoma cell lines

Objective： The aim of this study was to investigate the relationship between p38MAPK activity and apoptosis during the drug resistance of breast carcinoma cell lines. Methods： Using p38MAPK special inhibitor SB203580 to analyze the effect on the cell apoptosis of MCF-7/ADM cell. Cell apoptosis was analysed by PI staining and flow cytometry （FCM） （F test）. 50% inhibition concentration （IC50） of adriamycin on MCF-7/ADM was determined by MTT method （F test） in vitro. MDR-1 mRNA expression was detected by RT-PCR （F test） and Western Blot （F test） respectively. Results： After SB203580 24 h action the MCF-7/ADM＇s apoptosis rate was 26.73±4.90%, higher than the control group and untreated group （F = 143.80, P 〈 0.001）. The sensitity to the ADM was improved significantly （F = 148927.1, P 〈 0.001）, and the reversal effect of treat SB203580 group was 68.45%. The P38MAPK protein （F= 685.419, P 〈 0.001） and MDR-1 mRNAexpression after SB203580 24 h action were lower than the control group and untreated group （F = 9139.24, P 〈 0.001）. Conclusion： P38MAPK signal way plays an important role in drug resistance of breast carcinoma ceil. p38MAPK can protect MCF-7/ADM cells from apoptosis, and blocking the p38MAPK signal way can increase the apoptosis for breast carcinoma drug resistance cell lines.

Foxp3 rs2294021 polymorphism contributes to the susceptibility to breast carcinoma

Objective:Foxp3,the main regulator of Treg (regulatory T) cells, is down-regulated in breast carcinoma and other cancers. The rs2294021 Foxp3 polymorphism contributes to Foxp3 down-regulation, thereby weakens its tumor suppressing activity. The aim of our study was to evaluate the potential influence of Foxp3 polymorphism on breast cancer, we conducted a case-control study in Han Chinese women. Methods: Foxp3 genotyping was conducted in 677 breast carcinoma patients and 828 age-frequency matched cancer-free controls. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Experiment data was analyzed using Chi-square test and SPSS software. Results: The T/C genotype was found to be significantly associated with increased risk of breast carcinoma occurrence (OR = 1.462; 95% CI 1.165-1.833, P = 0.001) compared with the T/T or C/C (OR 1.143; 95% CI 0.838-1.559, P = 0.397) genotype. The increased risk for breast carcinoma related to heterozygous genotype was more pronounced in subjects over 50 years (OR 1.631; 95% CI 1.116-2.383, P = 0.011). No significant association was found between the polymorphism and the ER/PR status, metastasis or tumor stage of breast cancer. Conclusion: Our findings suggest that rs2294021 Foxp3 polymorphism may be a potential contributor for development of breast carcinoma in Han Chinese women.