OBJECTIVETo explore the pathogenesis and significance of neuroendocrine breast carcinoma by detecting chromogranin A (CgA) in human mammary tissues.

METHODEighty-nine cases of human mammary tissues were collected to detect CgA expression using immunohistochemistry.

RESULTNo CgA expression was detected in normal or hyperplastic tissues, but its expression was found in mammary carcinoma tissues at the rate of 16.7%. A significant difference in CgA expression was found between cancer tissues and non-cancer tissues, but not between the cancer tissues with different pathological grades.

CONCLUSIONThe pathogenesis of mammary neuroendocrine carcinoma may involve the micro-environmental factors that affect the differentiation of stem cells to give rise to immature cells, cell differentiation in other lineages or transdifferentiation. CgA may serve as an immunological parameter for this type of breast cancer in routine screening test.

Breast ; metabolism ; Breast Neoplasms ; metabolism ; Carcinoma, Neuroendocrine ; etiology ; metabolism ; Chromogranin A ; metabolism ; Female ; Humans

Cyclin/cdc complexes are known to function in cell-cycle regulation. Cyclin D1/cdk4 and -6 complexes, which functions as a G1-S checkpoint and cyclin B1/cdc2 complexes, a G2-M checkpoint are essential for DNA synthesis and mitosis, respectively. Thus, dysregulated overexpression of cyclins appears to be involved in uncontrollable cell proliferation and early tumor development. We investigated the expression and proliferative index of cyclin D1 (PIcyclin D1), cyclin B1 (PIcyclin B1) and Ki-67 (PIKi-67) using immunohistochemical staining on 15 cases of ductal hyperplasia (DH), 26 cases of atypical ductal hyperplasia (ADH) and 43 cases of ductal carcinoma in situ (DCIS) of the breast in order to evaluate whether these cyclins are associated with abnormal cell proliferation and play a role in tumor development from ADH to carcinoma. Furthermore, we investigated whether the expression and proliferative index of the cyclins and Ki-67 are correlated with the histologic grade according to the Van Nuys classification and with the histologic subtype according to traditional classification. Finally, we estimated the correlation coefficient among PIcyclin D1, PIcyclin B1, PIKi-67 and estrogen receptor in ADH and DCIS. The expression of cyclin D1 was detected in 39.5% of DCIS and 7.7% of ADH cases. In the DH cases, expression of cyclin D1 was not found. Expression of cyclin B1 was also detected in 69.7% of DCIS, 50.0% of ADH and 93.3% of the DH cases. The PIcyclin D1 was significantly different among these three groups. Moreover, the PIcyclin D1 and PIKi-67 were differed significantly between the low grade DCIS and ADH cases. However, PIcyclin B1 only appeared to be significantly different between the total DCIS and ADH. Results of the correlation coefficient among PIcyclin D1, PIcyclin B1 and PIKi-67 were positively correlated with each other. No significant correlation was found between the expression of ER and cyclin D1 in ADH and DCIS. In summary, our results support the hypothesis that a cyclin D1 and cyclin B1 protein aberration, along with Ki-67, may act as a relatively early event in the tumor development from ADH to carcinoma.
Breast/pathology* ; Breast/metabolism* ; Breast Neoplasms/pathology* ; Breast Neoplasms/metabolism* ; Carcinoma, Infiltrating Duct/pathology* ; Carcinoma, Infiltrating Duct/metabolism* ; Cyclins/metabolism* ; Female ; Human ; Hyperplasia ; Ki-67 Antigen/metabolism

Breast Neoplasms/metabolism* ; Female ; Humans ; Receptor, ErbB-2/metabolism*

OBJECTIVESTo investigate the intralaboratory reproducibility of immunohistochemistry (IHC) testing for HER2 status in breast cancer, and to evaluate the factors which influence the reproducibility. The concordance between monoclonal antibody CB11 and HercepTest was also assessed.

METHODSHER2 overexpression on paraffin sections from thirty-seven cases of breast invasive ductal carcinoma was evaluated using CB11 and the evaluation procedure had been repeated for five times scored the tests together according to the HercepTest and new American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) grading schemes by 2 experienced pathologists together. Reproducibility rates of the five rounds were assessed using Kappa statistic, and the results from two scoring systems were compared. HercepTest kit was applied to the same cases afterward and the results were compared with CB11.

RESULTSSubstantial intralaboratory reproducibility was achieved among 5 rounds tests. Excluding the influence effect of changing antibody lots, the intralaboratory reproducibility was closed to the perfect threshold (Kappa = 0.7858, HercepTest scheme). The results derived from the two grading schemes had an almost perfect agreement (Kappa = 0.8549). The concordance (positive vs. negative) between CB11 and HercepTest was 83.78%.

CONCLUSIONSLaboratory work with strict supervision and more experience will ensure a reliable testing consistency. Reproducibility analysis could be adopted to evaluate the intralaboratory staining quality on HER2 testing. Different antibody lots bring some influence to the intralaboratory reproducibility, but not significant. CB11 could be accepted to screen HER2 status in routine practice after testing validation.

Antibodies, Monoclonal ; metabolism ; Breast Neoplasms ; metabolism ; Carcinoma, Ductal, Breast ; metabolism ; Female ; Humans ; Immunohistochemistry ; methods ; Receptor, ErbB-2 ; metabolism ; Reproducibility of Results

Adenocarcinoma, Mucinous ; metabolism ; Breast Neoplasms ; metabolism ; Female ; Humans ; Neoplasm Proteins ; metabolism ; Receptor, ErbB-2 ; metabolism

Cancer stem cells (CSCs), a subpopulation of cancer cells with ability of initiating tumorigenesis, exist in many kinds of tumors including breast cancer. Cancer stem cells contribute to treatment resistance and relapse. Conventional treatments only kill differentiated cancer cells, but spare CSCs. Combining conventional treatments with therapeutic drugs targeting to CSCs will eradicate cancer cells more efficiently. Studying the molecular mechanisms of CSCs regulation is essential for developing new therapeutic strategies. Growing evidences showed CSCs are regulated by non-coding RNA (ncRNA) including microRNAs and long non-coding RNAs (lncRNAs), and histone-modifiers, such as let-7, miR-93, miR-100, HOTAIR, Bmi-1 and EZH2. Herein we review the roles of microRNAs, lncRNAs and histone-modifiers especially Polycomb family proteins in regulating breast cancer stem cells (BCSCs).
Breast Neoplasms ; genetics ; metabolism ; pathology ; Histones ; metabolism ; Humans ; Neoplastic Stem Cells ; metabolism ; RNA, Untranslated ; genetics ; metabolism

Tumor PET imaging with radiopharmaceuticals plays a major role in the understanding of tumor biological information and for diagnosis of tumorswith non-invasive methods. These radiopharmaceuticals can be divided into two categories radiopharmaceuticals for metabolic process imaging and for specific receptor imaging. Most tumor imaging radiopharmaceuticals such as [18F]FDG, [18F]FLT, and [11C]choline can be trapped in tumor cells by specific metabolic processes of each radiopharmaceutical and show an increase in metabolism of tumor regions. Unlike these compounds, the hypoxia imaging adiopharmaceuticals such as [18F]FMISO and [64Cu]ATSM are trapped by oxidative metabolic mechanisms under only hypoxic conditions of tumor cells. For tumor specific receptor imaging, [18F]FES for estrogen receptor positive breast cancer may be used and recent clinical results showed the possibility of evaluating tumor therapy responseby estrogen receptor imaging with [18F]FES. This paper gives an overview of the current status of tumor PET imaging adiopharmaceuticals and the development of new lead compounds as potential radiopharmaceuticals by medicinal chemistry.
Anoxia ; Breast Neoplasms ; Chemistry, Pharmaceutical ; Diagnosis ; Estrogens ; Metabolism ; Radiopharmaceuticals*

OBJECTIVE: To study the expression of PTEN, p53 and epidermal growth factor receptor (EGFR) in the molecular subtypes of breast carcinoma and to evaluate the correlations with triple-negative breast cancer.
 METHODS: Immunohistochemical MaxVision(TM) method was used to detect the expression of PTEN, p53, EGFR, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) in 291 cases of infiltrating ductal carcinoma of breast. 
 RESULTS: The positive expression of PTEN, p53 and EGFR protein in breast carcinoma was 57.0%, 57.0% and 38.5%, respectively, which were significantly different from those in benign breast diseases (P<0.05). The expression of PTEN or EGFR in breast cancer was correlated with tumor size, histological grade, lymph node metastasis, TNM stage, ER and HER2 status (P<0.05); the expression of p53 was correlated with tumor size, histological grade and ER status (P<0.05). The difference of positive expression rates of PTEN, p53 and EGFR protein among different subtypes including luminal A, luminal B (HER2-), luminal B (HER2+), HER2 over-expression and triple-negative was statistically significant (P<0.05). There were close correlations among PTEN, p53 and EGFR in the triple-negative subtype (P<0.05).
 CONCLUSION Low expression of PTEN and high expression of EGFR and p53 are observed in triple-negative breast cancer, which may synergistically contribute to the pathogenesis of triple-negative breast cancer.
Breast Neoplasms ; classification ; metabolism ; pathology ; Carcinoma, Ductal, Breast ; metabolism ; pathology ; Female ; Humans ; Lymphatic Metastasis ; PTEN Phosphohydrolase ; metabolism ; Receptor, ErbB-2 ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Triple Negative Breast Neoplasms ; metabolism ; pathology ; Tumor Suppressor Protein p53 ; metabolism

PURPOSE: The aim of this study was to determine whether plasma lecithin:cholesterol acyltransferase (pLCAT) and erythrocyte membrane Na(+)-K(+)-ATPase ase (emNaKATPs) activity have a correlation in breast cancer. This study compared these parameters at time points before and after treatment with radiotherapy. METHODS: The levels of pLCAT and emNaKATPs were assessed in 30 patients with breast carcinoma and 20 control subjects. While emNaKATPs was measured with spectrophotometric method, pLCAT levels was measured using a specific enzyme-linked immunosorbent assay. RESULTS: pLCAT levels, both before and after radiotherapy, were found to be decreased in breast cancer patients than in the controls groups (p<0.001 and p<0.001, respectively). Also, pLCAT levels after radiotherapy were found to be decreased in breast cancer patients than the pLCAT levels before radiotherapy (p<0.001). The emNaKATPs activity were higher in the control group than in the breast cancer patients before/after radiotherapy (RT) (p<0.001 and p<0.001, respectively). At the same time, emNaKATPs activity before RT was higher in the breast cancer patients than emNaKATPs activity after RT (p<0.001). There was a significant correlation between pLCAT and emNaKATPs activity in breast cancer patients receiving radiotherapy (r=0.63, p<0.001), but no correlation between in breast cancer patients before RT and control group (r=0.023, p>0.05). CONCLUSION: The results of the present study demonstrated that decreased pLCAT and emNaKATPs activity levels in breast cancer patients after/before RT than control group. In addition, decreased emNaKATPs activity in breast cancer patients receiving radiotherapy may be due to decreased pLCAT concentrations and RT beam. In our opinion, altered activities of pLCAT and emNaKATPs are linked to the treatment effect of radiotherapy. These data may clarify the development of cell membrane dysfunction and lipid metabolism in breast cancer patients receiving radiotherapy.
Breast ; Breast Neoplasms ; Cell Membrane ; Cholesterol ; Erythrocyte Membrane ; Humans ; Lecithins ; Lipid Metabolism ; Plasma ; Sterol O-Acyltransferase

OBJECTIVETo study the expression of fascin-1 protein in breast cancer and to evaluate its correlation with clinicopathologic features of the tumor.

METHODSImmunohistochemical EnVision method was performed to evaluate the expression of fascin-1 in 23 cases of normal breast tissues, 69 cases of benign breast lesions, 58 cases of usual ductal hyperplasia (UDH), 61 cases of ductal carcinoma in situ (DCIS) and 221 cases of breast cancer from March 2007 to December 2011.

RESULTSFascin-1 protein expression rates in normal breast tissues, benign breast lesions, UDH, DCIS and breast cancer were 100.0% (23/23), 89.9% (62/69), 13.8% (8/58), 19.7% (12/61), and 42.1% (93/221), respectively. Fascin-1 expression in normal breast tissues and benign breast lesions was significantly higher than those in UDH, DCIS and breast cancer (P < 0.01); Fascin-1 expression in breast cancer was significantly higher than those in UDH and DCIS (P < 0.01). There was a tendency of increased fascin-1 expression in DCIS compared to UDH, but the difference was not statistically significant (P > 0.05). Fascin-1 positive rates in patients with DCIS grade III (26.8%, 11/41) was significantly higher than that in patients with DCIS grade I-II (1/20, P < 0.05). Fascin-1 protein expression in breast cancer increased with increasing histologic grade and clinical stage (P < 0.01). Fascin-1 protein expression was also significantly higher in tumors with negative estrogen receptor (ER) and progestone receptor (PR) status and > 3 axillary lymph node metastases compared to tumors that were ER and PR positive and ≤ 3 axillary lymph node metastases (P < 0.01 and P < 0.05, respectively). Logistic regression analysis showed that fascin-1 expression correlated positively with high clinical stage (OR = 1.568, 95% CI = 1.029-2.387, P < 0.05) , but negatively with ER expression (OR = 0.149, 95% CI = 0.079-0.281, P < 0.01) .

CONCLUSIONSFascin-1 is highly expressed in normal breast tissues and benign breast lesions, suggesting that it may be a biological marker of mature mammary ductal epithelium. Fascin-1 protein expression shows a significantly increasing trend from UDH, DCIS to invasive breast cancer, suggesting that fascin-1 plays an important role in breast carcinogenesis and may be a potential target for therapy.

Axilla ; Breast ; metabolism ; pathology ; Breast Neoplasms ; metabolism ; pathology ; Carcinoma in Situ ; metabolism ; pathology ; Carcinoma, Ductal, Breast ; metabolism ; pathology ; Carrier Proteins ; metabolism ; Estrogen Receptor alpha ; metabolism ; Female ; Humans ; Hyperplasia ; metabolism ; Lymph Nodes ; metabolism ; Lymphatic Metastasis ; Microfilament Proteins ; metabolism ; Receptors, Estrogen ; metabolism