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

OBJECTIVETo evaluate the application of the immunohistochemistry (IHC) and the fluorescence in situ hybridization (FISH) in detecting the amplification and the expression of HER-2 gene in the breast cancer patients.

METHODSSixty-six cases of paraffin-embeded breast cancer samples with overexpression, low or no expression of HER-2 gene as detected by IHC were analyzed for HER-2 gene amplification using FISH.

RESULTSAmong the 42 samples with HER-2 gene overexpression (3+/2+) detected by IHC, 31 showed positive HER-2 gene amplification and 11 showed negative HER-2 gene amplification in FISH. In the 24 samples with low or no HER-2 gene expression (1+/-) detected by IHC, no HER-2 gene amplification was detected by FISH. The results of the two testing methods showed a good consistency with the kappa coefficient of 0.672 (P<0.001). We also found that the 17 chromosome polysomy in 42% of the samples and the incidence of 17 polysomy was significantly higher in the HER-2 gene overexpression (3+/2+) group than in low or no HER-2 gene expression (1+/-) group (chi(2)=4.688, P=0.03).

CONCLUSIONIHC can be used as a screening method for detecting HER-2 gene amplification, and FISH should be performed in cases of HER-2 gene overexpression (3+/2+) as detected by IHC.

Breast Neoplasms ; genetics ; metabolism ; Carcinoma, Ductal, Breast ; genetics ; metabolism ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Receptor, ErbB-2 ; analysis ; genetics

OBJECTIVETo make quantitative analysis of DNA content of breast cancer with neuroendocrine (NE) cells and its significance.

METHODSUsing MIPS-III image analyzer, DNA content and 9 parameter measurements of the tumor nuclei were made in both NE positive (17) and negative (64) breast carcinomas.

RESULTSOut of 81 breast carcinomas, 17 cases were NE positive while 64 cases were NE negative. In the NE (+) cases, the integral optic density, mean optic density, DNA index, DNA stemlines peak, > 5c aneuploidy cells and the rate of aneuploidy cells were all lower than those in the NE negative breast carcinoma cases (P < 0.01). The positive rates of NE cells were 32.5% and 7.9% in grade I - II breast carcinomas and in grade III breast carcinomas respectively with significant difference between the two groups (P < 0.01).

CONCLUSIONOur study shows that NE (+) breast carcinomas have lower DNA parameters than NE (-) breast carcinomas, suggesting that NE (+) breast carcinomas have lower malignancy.

Aneuploidy ; Breast Neoplasms ; genetics ; pathology ; Carcinoma, Neuroendocrine ; genetics ; pathology ; DNA, Neoplasm ; genetics ; metabolism

OBJECTIVETo explore the role of TBX3 gene in the pathogenesis of breast cancer.

METHODSThe total RNA of 51 fresh breast cancer tissues and the corresponding adjacent tissues were extracted and reverse transcribed into cDNA to detect the expression of TBX3 mRNA by real-time PCR. The correlation between TBX3 mRNA expression and the clinicopathologic parameters in relation to breast cancer metastasis was analyzed.

RESULTCompared to that in the adjacent tissues, the expression of TBX3 mRNA was markedly increased in breast cancer tissues. TBX3 mRNA expression was significantly higher in metastatic breast cancer than in non-metastatic tumors.

CONCLUSIONIncreased expression of TBX3 mRNA suggests the involvement of TBX3 in the pathogenesis and metastasis of breast cancer.

Breast Neoplasms ; etiology ; genetics ; pathology ; Female ; Humans ; Neoplasm Metastasis ; genetics ; RNA, Messenger ; genetics ; metabolism ; T-Box Domain Proteins ; genetics ; metabolism

OBJECTIVETo study the expression of prostate stem cell antigen (PSCA) at protein and mRNA levels in invasive micropapillary carcinoma of the breast (IMPC) and to analyze the relationship between PSCA expression and clinicopathologic features.

METHODSThe expression of PSCA protein was analyzed by immunohistochemistry (LSAB) in 66 cases of IMPC and 67 cases of invasive ductal carcinoma, not otherwise specified (IDC-NOS). The association between PSCA expression and clinicopathologic features was also analyzed in IMPC. Furthermore, RT-PCR was used to detect PSCA mRNA in 10 cases of primary IMPC and 10 cases of primary IDC-NOS with paired normal breast tissues, each from the same subject.

RESULTSImmunohistochemical analysis revealed the overexpression of PSCA in 47 of 66 (71.2%) cases of IMPC and 35 of 67 (52.2%) IDC-NOS. Statistical analysis showed a significant difference of PSCA expression between IMPC and IDC-NOS (P = 0.024). In IMPC, the expression of PSCA was correlated with lymph nodes metastasis (P = 0.039). RT-PCR showed the mRNA level of PSCA was significantly higher in primary IMPC and IDC-NOS tissue than that in paired normal breast tissue (7/10 and 5/10, respectively), and it was also significantly higher in primary IMPC tissue than that in IDC-NOS tissue.

CONCLUSIONPSCA might play an important role in lymph node metastasis in IMPC.

Antigens, Neoplasm ; genetics ; metabolism ; Breast Neoplasms ; genetics ; metabolism ; pathology ; Carcinoma, Ductal, Breast ; genetics ; metabolism ; pathology ; Carcinoma, Papillary ; genetics ; metabolism ; pathology ; Female ; GPI-Linked Proteins ; genetics ; metabolism ; Humans ; Lymphatic Metastasis ; Neoplasm Invasiveness ; Neoplasm Proteins ; genetics ; metabolism ; Neoplasm Staging ; RNA, Messenger ; metabolism

OBJECTIVETo study the expression level and significance of glucose transporter 1 (Glut-1) in normal breast tissue, adenosis, adenoma and breast carcinoma.

METHODSA total of 147 cases of female breast tissue samples, including 92 cases of invasive ductal carcinoma, 26 cases of breast fibroadenoma, 24 cases of breast adenosis and 5 cases of normal breast tissues, were collected for quantitative detection of the expression of Glut-1 protein by immunohistochemistry (EnVision method) and Western blot, and its mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR).

RESULTSIn normal breast tissue and benign lesions of the breast, Glut-1 was undetectable or only weakly detectable in cytoplasm of ductal and acinar epithelia. In contrast, the intensity of Glut-1 staining was significantly higher in invasive ductal carcinomas (P = 0.0002) with protein expression predominantly in cellular membrane and lesser in cytoplasm. Western blot and RT-PCR analyses showed that the expression of Glut-1 protein and mRNA were significantly increased in invasive ductal carcinoma than fibroadenoma (P =0.001 for protein; P <0.05 for mRNA) and adenosis (P =0.001 for protein; P < 0.05 for mRNA). There was a significant difference among groups (P = 0.0002 for protein; P = 0.0001 for mRNA).

CONCLUSIONSGlucose transport activity, as indicated by Glut-1 protein and its mRNA expression, significantly increases in breast carcinoma than non-cancerous lesions. The over-expression of Glut-1 in breast carcinoma is tightly coupled with tumor cell proliferation, invasion and metastasis, implying that Glut-1 may serve as a new marker in the early diagnosis and prognostication of breast malignancy as well as a new therapeutic target.

Breast Neoplasms ; metabolism ; Carcinoma, Ductal, Breast ; metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Glucose ; physiology ; Glucose Transport Proteins, Facilitative ; genetics ; metabolism ; Glucose Transporter Type 1 ; genetics ; metabolism ; Humans ; Prognosis

Breast Neoplasms ; metabolism ; pathology ; Female ; Humans ; Ki-67 Antigen ; genetics ; metabolism

Antigens, Neoplasm ; genetics ; metabolism ; Breast Neoplasms ; enzymology ; genetics ; metabolism ; DNA Topoisomerases, Type II ; genetics ; metabolism ; DNA-Binding Proteins ; genetics ; metabolism ; Female ; Gene Expression Regulation, Neoplastic ; physiology ; Humans

OBJECTIVETo investigate the relationship between positive expression of Her2 and abnormal expressions of beta-catenin and E-cadherin and its implications.

METHODSImmunohistochemistry was used to detect the expressions of Her2, beta-catenin and E-cadherin in 147 samples of human breast carcinoma. The expressions of beta-catenin and E-cadherin were also detected in 19 tissues adjacent to the carcinoma and 17 benign breast lesions as controls.

RESULTSIn breast carcinoma, positive Her2 expression was associated with lymph node metastasis, advanced clinical stage and negative expression of ER and PR (P<0.05). Abnormal beta-catenin expression was associated with positive lymph node status and high histological grade (P<0.01). Abnormality of E-cadherin expression was related to lymph node metastasis and advanced clinical stage (P<0.05). Abnormal beta-catenin expression was directly correlated with abnormal E-cadherin expression (P<0.01). Her2 positivity showed a direct correlation to abnormal beta-catenin expression (P<0.01), and they cooperated in promoting axillary lymph node metastasis in human breast carcinoma (P<0.01).

CONCLUSIONA direct correlation between positive Her2 expression and abnormal beta-catenin expression exists in human breast carcinoma, and positive Her2 expression may have functional interactions with abnormal activation of Wnt/beta-catenin signaling pathway.

Adult ; Aged ; Breast Neoplasms ; metabolism ; pathology ; Cadherins ; metabolism ; Carcinoma, Ductal, Breast ; metabolism ; pathology ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Receptor, ErbB-2 ; metabolism ; beta Catenin ; genetics ; metabolism

OBJECTIVETo evaluate the sensitivity and specificity of chromogenic in-situ hybridization (CISH) in detecting HER2 gene amplification in breast carcinomas.

METHODSHER2 oncogene amplification and its protein expression in 165 cases of breast carcinoma were investigated by immunohistochemistry (IHC) and CISH.

RESULTS(1) CISH did not detect HER2 gene amplification in 107 cases of IHC negative tumors and 24 cases of IHC 1+ tumors. (2) CISH identified high copy numbers of HER2 gene amplification in 21/22 (95.5%) cases with IHC 3+. (3) In 12 HIC 2+ cases, CISH identified 3 cases of high copy number amplification, 6 cases of low copy number amplification and 3 cases without amplification.

CONCLUSIONSHER2 gene amplification detection by CISH is highly sensitive and has a high concordance with IHC detection of the protein expression. It is concluded that CISH is a tool to evaluate HER2 gene status in breast cancer and can be an implement in conventional pathology laboratories.

Breast Neoplasms ; genetics ; metabolism ; pathology ; Carcinoma, Ductal, Breast ; genetics ; metabolism ; pathology ; Carcinoma, Intraductal, Noninfiltrating ; genetics ; metabolism ; pathology ; Carcinoma, Lobular ; genetics ; metabolism ; pathology ; Chromogenic Compounds ; Female ; Gene Amplification ; Humans ; Immunohistochemistry ; methods ; In Situ Hybridization ; methods ; Receptor, ErbB-2 ; genetics ; metabolism