OBJECTIVETo investigate the progesterone-binding site on the normal fertile human sperm membrane after 2 hours of in vitro capacitation.

METHODSViable spermatozoa were selected by a swim-up method. After 2 hours of in vitro capacitation, multipoint saturation binding experiments were performed. Sperm suspension and increasing concentrations of progesterone-11alpha-glucuronide-[125I] iodotyramine (125I-P) were added to 7 total binding tubes respectively, and equal amounts of sperm suspension and 125I-P were added to another 7 corresponding non-specific binding tubes in the presence of 10 micromol/L progesterone. After incubation for 1 hour at 4 degrees C, the radioactivity of both the tubes and the pellets after centrifugation was measured respectively. The equilibrium dissociation constant (Kd) and maximum binding capacity (Bmax) were calculated using the mathematical model of single site multi-point saturation method of Scatchard function and least-squares regression.

RESULTSKd was (0.61 +/- 0.04) nmol/L and Bmax was (830 +/- 344) sites/cell. The significance test of the regression equation indicated that r = -0.980, P < 0.01.

CONCLUSIONThere is a high affinity and low capacity binding site for the progesterone (progesterone receptor) on the normal fertile human sperm membrane.

Adult ; Cell Membrane ; chemistry ; Humans ; Male ; Progesterone ; Radioligand Assay ; Receptors, Progesterone ; analysis ; Sperm Capacitation ; Spermatozoa ; chemistry

Antibodies ; Breast Neoplasms ; chemistry ; Female ; Humans ; Immunohistochemistry ; Neoplasm Proteins ; analysis ; Receptors, Estrogen ; analysis ; immunology ; Receptors, Progesterone ; analysis ; immunology

Breast Neoplasms ; chemistry ; pathology ; Cytodiagnosis ; methods ; Cytological Techniques ; methods ; Female ; Humans ; Immunohistochemistry ; methods ; Receptors, Estrogen ; analysis ; Receptors, Progesterone ; analysis

OBJECTIVESTo observe the expression of somatostatin receptor subtype 2 (SSTR2) mRNA, and investigate the relationship between the expression of SSTR2 mRNA and the expressions of estrogen and progesterone receptors (ERs and PRs) in benign and malignant breast tissues.

METHODSSamples from a total of 23 breast carcinomas, 16 mammary hyperplasias, and 9 mammary fibroadenomas were analyzed. SSTR2 mRNA expression was examined by in situ hybridization using multiphase oligoprobes. ER and PR expressions were detected by immunohistochemical staining. A computerized image analysis system was utilized to estimate the relative content of SSTR2 mRNA.

RESULTSThe rate of expression (87.0%) and relative content (0.47) of SSTR2 mRNA in breast cancer were higher than those in benign breast tissue (64%, 0.26) (P < 0.05). SSTR2 mRNA expression was closely correlated with ER and PR expressions in breast cancer (P < 0.05). SSTR2 mRNA was also positively correlated with ER expression in benign breast tissues.

CONCLUSIONSSSTR2 mRNA expression is higher or in benign breast tissues than in malignant ones. There is a significant positive correlation between SSTR2 mRNA and ER and PR expressions. Combined antiestrogen and somatostatin analogue in treatment of ER-positive breast cancers should be further investigated.

Breast Diseases ; metabolism ; Breast Neoplasms ; chemistry ; Humans ; Immunohistochemistry ; In Situ Hybridization ; RNA, Messenger ; analysis ; Receptors, Estrogen ; analysis ; Receptors, Progesterone ; analysis ; Receptors, Somatostatin ; genetics

PURPOSE: A growing body of evidence indicates that zoledronic acid (ZA) can improve the clinical outcome in patients with breast cancer and low estrogen levels. In the present study, we aimed to investigate the survival benefit of ZA administration in postmenopausal Korean women with breast cancer who were also receiving aromatase inhibitors. METHODS: Between January 2004 and December 2010, 235 postmenopausal breast cancer patients undergoing aromatase inhibitor therapy were investigated. All patients were postmenopausal, as confirmed by laboratory tests. Of these patients, 77 received adjuvant upfront ZA for at least 1 year in addition to conventional adjuvant treatment. The remaining 158 patients never received ZA and were treated according to the St. Gallen guidelines. RESULTS: The baseline characteristics for ZA treatment were not different between the two groups. The median follow-up time was 62 months, and the patients who received ZA in addition to aromatase inhibitors showed a better recurrence-free survival compared to those who received aromatase inhibitors alone (p=0.035). On multivariate analysis, the patients who received ZA showed a better recurrence-free survival independent of the tumor size, nodal status, progesterone receptor, and histological grade. For this model, Harrell c index was 0.743. The hazard ratio of ZA use for recurrence-free survival was 0.12 (95% confidence interval, 0.01-0.99). CONCLUSION: Our findings suggest that upfront use of ZA as part of adjuvant treatment can offer a survival benefit to postmenopausal breast cancer patients receiving aromatase inhibitor treatment.
Aromatase ; Aromatase Inhibitors* ; Breast Neoplasms* ; Estrogens ; Female ; Follow-Up Studies ; Humans ; Multivariate Analysis ; Postmenopause ; Receptors, Progesterone

PURPOSE: This study aimed at evaluating the pattern of changes in estrogen receptor (ER), progesterone receptor (PR) and the HER2 expression in primary and recurrent breast cancer. METHODS: In the study, we analyzed the changes of the ER and PR and the HER2 immunohistochemical expression to identify the patterns of changes and the predictive factors for the changes in 153 patients with primary and recurrent breast cancer between 1991 and 2005. RESULTS: There was a significant decrease in the positive rate of ER (50.3% to 38.6%, p<0.001), PR (43.8% to 26.8%, p=0.0095) and the HER2 (40.3% to 36.3%, p<0.001) expression in the primary breast cancers and recurrent breast cancers. The rate of triple negativity (ER/PR/HER2: all negative) was increased from 25.8% to 43.5% (p<0.001). Among 44 (28.6%) patients with changes in ER and ER status changed from positive to negative in 31 patients (20.3%) and negative to positive in 13 patients (8.3%) (p=0.007). For 58 patients (37.9%) who showed a change of the PR, the PR status changed from positive to negative in 42 patients (27.5%) and vice versa in 16 patients (10.4%) (p=0.0006). Twenty one patients (16.9%) changed from HER2 positive to HER2 negative and vice versa in 9 patients (7.3%) (p=0.029) among the 30 patients (24.2%) with changes in the HER2 expression. A multivariate analysis indicated that hormonal therapy was a significant factor that had an influence on the ER (odds ratio, 4.4) and PR (odds ratio, 2.6) changes. There were no significant differences in the survival rates according to the changes of the ER and PR, and the HER2 expression. CONCLUSION: The more common changes from positive to negative among the ER, PR, and HER2 indicated poor tumor biology of recurrent tumor. Therefore, the assessment of the ER, PR, and HER2 statuses is important for effectively treating recurrent breast cancer and especially those who have a previous history of hormonal therapy although survival benefit was not observed in this study.
Biology ; Breast ; Breast Neoplasms ; Estrogens ; Humans ; Multivariate Analysis ; Receptors, Progesterone ; Recurrence ; Survival Rate

PURPOSE: Survivin is a member of the inhibitors of apoptosis family. It has recently comes into the limelight as a promising tumor marker, but many previous reports have shown controversial results regarding the significance and prognostic value of a survivin expression. In this study we determined the correlation between the survivin expression and the conventional prognostic markers and we also investigated the outcomes according to the localization of the survivin expression. METHODS: Tissue microarray (TMA) blocks were made with formalin-fixed paraffin-embedded tissues from 185 breast cancer patients and the immunohistochemical staining was done using an anti-survivin antibody. Among these, 157 patients were available for a survivin expression. The conventional clinicopathologic features and overall survival were correlated with the localization of the survivin expression. RESULTS: Survivin was expressed in 101 breast cancers (64.3%). A higher cytoplasmic survivin expression were noted in the older group (p=0.003), in the node-negative cancers (p=0.012), in the earlier tumor stages (p=0.012) and in the cancers that had not been treated with adjuvant chemotherapy (p=0.014). On the contrary, a higher nuclear survivin expression was inversely correlated with an estrogen expression (p=0.006) and a progesterone receptor (p=0.043) expression. In terms of survival, a cytoplasmic expression was associated with improved overall survival (p=0.01) but a nuclear survivin expression was correlated with unfavorable overall survival (p=0.002). A high cytoplasmic to nuclear ratio of survivin was associated with improved overall survival (p=0.001) conversely, increased nuclear to cytoplasmic survivin ratio was correlated with unfavorable overall survival (p<0.0001). Multivariate analysis revealed that nuclear survivin expression (p=0.001) and high nuclear to cytoplasmic survivin ratio (p=0.012) were independent predictor of overall survival. CONCLUSION: Survivin is frequently expressed in primary breast cancer. A cytoplasmic survivin expression is a good prognostic predictor for patients with axillary node negative early breast cancers and a nuclear survivin expression is a worse independent predictor of overall survival for patients with axillary node positive breast cancers.
Apoptosis ; Breast ; Breast Neoplasms ; Chemotherapy, Adjuvant ; Cytoplasm ; Estrogens ; Humans ; Multivariate Analysis ; Receptors, Progesterone

PURPOSE: This study was designed to assess the protein levels of transformation/transcription domain-associated protein (TRRAP) in invasive ductal breast carcinomas, and investigated the association between TRRAP and the clinicopathological features of breast cancer. METHODS: We examined TRRAP protein expression in 470 breast cancer tissues and normal breast tissues by tissue microarray to study the correlation between TRRAP expression and clinicopathological features. This was analyzed using the chi-square test. Kaplan-Meier survival curves and log-rank tests were applied to analyze the survival status. Cox regression was applied for multivariate analysis of prognosis. RESULTS: The data demonstrated that expression of TRRAP was significantly lower in breast carcinomas (36.6%) than in corresponding normal breast tissues (50.8%). In addition, TRRAP protein levels negatively correlated with tumor size, and indicated poor differentiation, increased nodal involvement, and low p53-positive rates. Analysis of survival revealed that lower TRRAP expression correlated with shorter survival time. Univariate analyses identified TRRAP and progesterone receptor as independent protective factors for breast cancer prognosis. However, Ki-67, tumor size, and nodal involvement appeared to be independent risk factors. CONCLUSION: The findings indicate a significant correlation between TRRAP protein levels and adverse prognosis in breast cancer. Therefore, TRRAP could be a prognostic biomarker for breast cancer. In addition, TRRAP is also a predictive biomarker of breast cancer treatment.
Biomarkers ; Breast Neoplasms* ; Breast* ; Kaplan-Meier Estimate ; Multivariate Analysis ; Prognosis ; Receptors, Progesterone ; Risk Factors

PURPOSE: The purpose of the study was to evaluate the effect of preoperative magnetic resonance imaging (MRI) on survival outcomes for breast cancer. METHODS: A total of 954 patients who had T1–2 breast cancer and received breast-conserving therapy (BCT) between 2007 and 2010 were enrolled. We divided the patients according to whether they received preoperative MRI or not. Survival outcomes, including locoregional recurrence-free survival (LRRFS), recurrence-free survival (RFS), and overall survival (OS), were analyzed. RESULTS: Preoperative MRI was performed in 743 of 954 patients. Clinicopathological features were not significantly different between patients with and without preoperative MRI. In the univariate analyses, larger tumors were marginally associated with poor LRRFS compared to smaller tumors (hazard ratio [HR], 3.22; p=0.053). Tumor size, histologic grade, estrogen receptor (ER), progesterone receptor (PR), hormonal therapy, and adjuvant chemotherapy status were associated with RFS. Larger tumor size, higher histologic grade, lack of ER and PR expression, and no hormonal therapy were associated with decreased OS. Tumor size was associated with LRRFS in the multivariate analyses (HR, 4.19; p=0.048). However, preoperative MRI was not significantly associated with LRRFS, RFS, or OS in either univariate or multivariate analyses. CONCLUSION: Preoperative MRI did not influence survival outcomes in T1–2 breast cancer patients who underwent BCT. Routine use of preoperative MRI in T1–2 breast cancer may not translate into longer RFS and OS.
Breast Neoplasms* ; Breast* ; Chemotherapy, Adjuvant ; Estrogens ; Humans ; Magnetic Resonance Imaging* ; Mastectomy, Segmental ; Multivariate Analysis ; Receptors, Progesterone

PURPOSE: The p53 gene is one of the most frequently mutated genes in breast cancer. We investigated the patterns and biologic features of p53 gene mutation and evaluated their clinical significance in Korean breast cancer patients. METHODS: Patients who underwent p53 gene sequencing were included. Mutational analysis of exon 5 to exon 9 of the p53 gene was carried out using polymerase chain reaction-denaturing high performance liquid chromatography and direct sequencing. RESULTS: A total of 497 patients were eligible for the present study and p53 gene mutations were detected in 71 cases (14.3%). Mutation of p53 was significantly associated with histologic grading (p<0.001), estrogen receptor and progesterone receptor status (p<0.001), HER2 status (p<0.001), Ki-67 (p=0.028), and tumor size (p=0.004). The most frequent location of p53 mutations was exon 7 and missense mutation was the most common type of mutation. Compared with patients without mutation, there was a statistically significant difference in relapse-free survival of patients with p53 gene mutation and missense mutation (p=0.020, p=0.006, respectively). Only p53 missense mutation was an independent prognostic factor for relapse-free survival in multivariate analysis, with an adjusted hazard ratio of 2.29 (95% confidence interval, 1.08-4.89, p=0.031). CONCLUSION: Mutation of the p53 gene was associated with more aggressive clinicopathologic characteristics and p53 missense mutation was an independent negative prognostic factor in Korean breast cancer patients.
Breast Neoplasms* ; Breast* ; Chromatography, Liquid ; Estrogens ; Exons ; Genes, p53 ; Humans ; Multivariate Analysis ; Mutation, Missense ; Receptors, Progesterone