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

Adenocarcinoma, Mucinous ; pathology ; Adult ; Breast ; metabolism ; pathology ; Breast Neoplasms ; metabolism ; pathology ; Carcinoma ; metabolism ; pathology ; Female ; Humans ; Keratins ; metabolism ; Metaplasia ; Mucin-1 ; metabolism ; S100 Proteins ; metabolism

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

Actins ; metabolism ; Adult ; Breast ; pathology ; Breast Neoplasms ; metabolism ; pathology ; surgery ; Female ; Humans ; Mammography ; Neoplasms, Muscle Tissue ; metabolism ; pathology ; surgery ; Vimentin ; 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

Adenocarcinoma, Mucinous ; pathology ; Adult ; Breast Neoplasms ; metabolism ; pathology ; surgery ; Carcinoma ; pathology ; Carcinoma in Situ ; metabolism ; pathology ; surgery ; Carcinoma, Ductal, Breast ; metabolism ; pathology ; surgery ; Diagnosis, Differential ; Female ; Fibrocystic Breast Disease ; metabolism ; pathology ; surgery ; Humans ; Hyperplasia ; Lactalbumin ; metabolism ; S100 Proteins ; metabolism

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

Animals ; Apoptosis ; Bone Neoplasms ; metabolism ; pathology ; Breast Neoplasms ; metabolism ; pathology ; Cell Proliferation ; Chondrosarcoma ; metabolism ; pathology ; Colorectal Neoplasms ; metabolism ; pathology ; Female ; Humans ; Male ; Ovarian Neoplasms ; metabolism ; pathology ; Prostatic Neoplasms ; metabolism ; pathology ; RNA, Messenger ; metabolism ; SOX9 Transcription Factor ; biosynthesis ; genetics ; physiology

Actins ; metabolism ; Breast ; cytology ; metabolism ; Breast Neoplasms ; metabolism ; pathology ; Cell Differentiation ; Female ; Humans ; Keratins ; metabolism ; Neoplastic Stem Cells ; metabolism ; pathology ; Signal Transduction ; Stem Cells ; cytology ; metabolism

OBJECTIVETo investigate the clinicopathological and immunohistochemical features, diagnosis and differential diagnosis of nipple adenoma of the breast.

METHODSMorphological observation and immunohistochemistry were applied to 18 cases of nipple adenoma with a review of the related literatures.

RESULTSThe neoplasms were localized at nipples or under the areola of breast, adherent to the epidermis, mainly composed of dilated ducts in a tubular appearance associated with fibrotic matrix. The glandular epithelium showed various type of proliferation, forming thick layers or complex structures such as papillae, micropapillae, tufts, fronds, arcades or bridges accompanying with solid or cribriform cell nests. The tumor cells were crowding, lack of an uniform morphology and polarity with intact myoepithelial cells around the ducts. By immunostaining, the glandular epithelium was diffusely positive for 34betaE12, patchily positive for CK5/6, and negative for p53 and c-erbB-2. The myoepithelium, positive for p63, smooth muscle actin and Calponin, was well preserved and outlining the ducts.

CONCLUSIONSNipple adenoma is an infrequent type of benign breast neoplasm, presenting as sclerosing papilloma, papillomatosis or florid sclerosing adenosis. It is easily confused with atypical ductal hyperplasia/low grade ductal carcinoma in situ, invasive ductal carcinoma or low grade adenosquamous carcinoma. A correct diagnosis is based on the peculiar location and morphology of the tumor, and immunohistochemistry is helpful in some cases.

Adenoma ; metabolism ; pathology ; surgery ; Adult ; Breast Neoplasms ; metabolism ; pathology ; surgery ; Carcinoma in Situ ; metabolism ; pathology ; Carcinoma, Adenosquamous ; metabolism ; pathology ; Carcinoma, Ductal, Breast ; metabolism ; pathology ; Diagnosis, Differential ; Female ; Humans ; Keratin-5 ; metabolism ; Keratins ; metabolism ; Middle Aged ; Nipples ; metabolism ; pathology ; surgery