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 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 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 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 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

OBJECTIVETo investigate telomerase gene expression in precancerous mammary lesion, such as atypical ductal hyperplasia and breast cancer and to study the relationship between expression and malignant transformation.

METHODSExpression of human telomerase genes (hTR) and human reverse transcriptase gene (hTRT) in 76 cases of mammary tissue was evaluated using in situ hybridization and included 50 cases of mammary hyperplasia, 6 of which were benign hyperplasia, 9 were mild atypical hyperplasia, 12 were moderate atypical hyperplasia, 23 were severe atypical hyperplasia and 26 were mammary cancer.

RESULTSThe expressions of hTR and hTRT mRNA were much weaker or negative in benign hyperplasia (16.6%, 0), weak to mild moderate in atypical hyperplasia (22.2%, 11.1%, 33.3%, 25.0%), strong in severe atypical hyperplasia (60.9%, 52.1%), and significantly strong in mammary cancer (88.5%, 80.8%). The difference between mild-moderate atypical hyperplasia, invasive ductal carcinoma and severe atypical hyperplasia was significant (P < 0.05) and the difference between severe atypical hyperplasia and intraductal carcinoma was not significant (P > 0.05).

CONCLUSIONTelomerase genes (hTR and hTRT) expressions are related to the transformation of atypical hyperplasia. Activated telomerase may play a role in mammary cancer development.

Breast ; metabolism ; pathology ; Breast Neoplasms ; genetics ; pathology ; DNA-Binding Proteins ; Female ; Gene Expression ; Humans ; Precancerous Conditions ; genetics ; pathology ; RNA ; genetics ; physiology ; RNA, Messenger ; analysis ; Telomerase ; genetics ; physiology

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

OBJECTIVEThis study was designed to investigate the significance of hTERT mRNA in breast carcinogenesis and to explore the diagnostic efficacy, and to study the effect of tumor suppressor gene p53 on the expression of hTERT mRNA.

METHODSThe expression of hTERT mRNA was examined by in situ hybridization in 12 cases of normal breast tissue nearby cancer, 7 of simple ductal hyperplasia, 20 of atypical hyperplasia, 18 of ductal carcinoma in situ and 25 with invasive ductal carcinoma. The expression of p53 protein were examined by immunohistochemistry in 43 carcinomas.

RESULTShTERT was not detected in normal breast tissue nearby cancer and simple ductal hyperplasia. The positive rate of hTERT mRNA in atypical hyperplasia, ductal carcinoma in situ and invasive ductal carcinoma were 25.0%, 83.3% and 88.0%, respectively. The prevalence and intensity of hTERT mRNA expression were much greater in carcinoma than those in simple or atypical hyperplasia and normal breast tissue nearby cancer (P < 0.05). The expression of hTERT was not correlated with tumor size and lymph node metastasis (P > 0.05). The positive correlation between hTERT mRNA and p53 was found in breast carcinoma (r = 0.5540, P < 0.01).

CONCLUSIONhTERT mRNA expression is closely related to the malignant transformation of breast tissue. Semi-quantitative detection of hTERT mRNA expression in situ is helpful in differentiated diagnosis of carcinoma in situ and atypical hyperplasia. Inactivation of p53 may play a role in the transcriptive activation of hTERT gene in breast carcinoma.

Adult ; Breast ; metabolism ; pathology ; Breast Neoplasms ; genetics ; metabolism ; pathology ; Carcinoma, Ductal, Breast ; metabolism ; pathology ; Carcinoma, Intraductal, Noninfiltrating ; metabolism ; pathology ; Diagnosis, Differential ; Disease Progression ; Humans ; Hyperplasia ; Lymphatic Metastasis ; Middle Aged ; RNA, Messenger ; biosynthesis ; genetics ; Telomerase ; biosynthesis ; genetics ; Tumor Suppressor Protein p53

Biopsy, Fine-Needle ; methods ; Breast ; metabolism ; pathology ; Breast Neoplasms ; diagnosis ; genetics ; pathology ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Lymph Nodes ; metabolism ; pathology ; Lymphoma ; diagnosis ; genetics ; pathology ; Pancreas ; metabolism ; pathology ; Pancreatic Neoplasms ; diagnosis ; genetics ; pathology

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