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1.  Male breast carcinoma: a clinicopathological and immunohistochemical characterization study 
Male breast carcinoma is a relatively rare disease. This study retrospectively investigated the clinicopathological features of 73 cases of male breast carcinoma in Chinese population, and classified the molecular subtype based on surrogate immunohistochemical definitions. The expression of GCDFP15, MGB, AR and FOXP1 were evaluated. Invasive carcinoma of no special type was the most common histological type in the study group (71.2%, 52/73). The luminal A and B subtypes were the major types of male breast carcinoma (60.9%, 34.8% respectively). AR and FOXP1 are expressed in 84.2% (48/57) and 71.9% (41/57) of the studied cases. Carcinoma of the luminal A subtype expressed GCDFP15 (73.5%, 25/34) and MGB (58.8%, 20/34) more frequently than cases of the luminal B subtypes (34.8%, 8/23 and 43.5%, 10/23, respectively; P = 0.004, P = 0.255, respectively). In conclusion, invasive carcinoma of no special type was the most common histological type in male breast carcinoma among Chinese population. Our study revealed that the luminal A and B subtypes were the major types of male breast carcinoma. AR and FOXP1 are highly expressed in male breast cancer. The luminal A subtype tends to express GCDFP15 and MGB more frequently than the luminal B subtype.
PMCID: PMC4230132  PMID: 25400768
Breast carcinoma; male; molecular subtype; immunohistochemistry
2.  Similar Prognoses for Invasive Micropapillary Breast Carcinoma and Pure Invasive Ductal Carcinoma: A Retrospectively Matched Cohort Study in China 
PLoS ONE  2014;9(9):e106564.
Purpose
Invasive micropapillary breast carcinoma (IMPC) is a rare pathological finding. Few studies have compared IMPC with invasive ductal breast carcinoma (IDC) according to matched nodal status and age. To better illustrate the difference between IMPC and IDC prognoses, we conducted this cohort study.
Methods
51 mixed or pure IMPC patients and 102 pure IDC patients were matched for nodal status and age. Clinical and biological features as well as disease-free survival (DFS) were compared between groups.
Results
More than one-half of IMPC consisted of mostly or exclusively IMPC component (meaning greater than 75%) and these tumors significantly correlated with a higher histologic grade (P = 0.016) and LVI positivity (P = 0.036) compared with mixed IMPC. IMPC displayed a significantly higher rate of estrogen receptor (ER) positivity and lymphovascular invasion (LVI) compared to matched IDC. Women diagnosed with IMPC had a slight, but not significant, reduced frequency for recurrence and metastasis compared to women with IDC (15.7% vs. 21.6%, P = 0.518). In the subgroup analysis, IMPC patients demonstrated significantly reduced survival (P = 0.018) compared to IDC patients in the T1N2–3 subpopulation, whereas IDC patients demonstrated significantly increased recurrence and metastasis (P = 0.024) compared to IMPC patients in the T2N2–3 subgroup. No difference was observed in patients with 3 or less positive lymph nodes (LNs).
Conclusion
Although no difference in DFS was observed between IMPC and LN-matched IDC patients, IMPC patients demonstrated a significantly poorer outcome compared to IDC patients with smaller tumors and 4 or more positive LNs. The opposite results were observed in larger tumors and patients with 4 or more positive LNs. Therefore, we might advise more proactive treatment for IMPC patients with a smaller tumor size and extensive LN involvement. Furthermore, correlative IMPC studies should focus on this subset of patients to elucidate the genetic and/or biologic differences that contribute to metastatic potential.
doi:10.1371/journal.pone.0106564
PMCID: PMC4154720  PMID: 25188383
3.  Carcinoma arising in microglandular adenosis of the breast: triple negative phenotype with variable morphology 
Carcinoma arising in microglandular adenosis (MGACA) is an extremely rare subtype of breast carcinoma. In this study, clinicopathological analysis of MGACA from 11 Chinese patients was conducted. Microscopically, all cases showed a spectrum of structure and glandular proliferations ranging from microglandular adenosis (MGA) to atypical MGA (AMGA) to MGACA. Carcinoma components were composed of high grade ductal carcinoma in situ (DCIS) in 1 case and invasive carcinoma in 10 cases. Invasive carcinomas were grade 3 in 10 tumors and grade 2 in 1. Invasive components in 5 of 10 cases were composed of invasive carcinoma of no special type (NST), and 1 case showed partially acinic cell differentiation. In 5 cases, invasive components were mixed of NST and matrix-producing carcinoma (MPC). All epitheliums in 11 cases were triple negative (ER-, PR-, HER2-), and diffuse positive for CK and S-100 protein. No myoepithelial cells were demonstrable from MGA to invasive components with immunohistochemical staining for P63 and calponin. PAS or reticulin stain showed the presence of a basement membrane around glands in MGA, AMGA, DCIS, and its absence in invasive components. Follow-up time ranged from 10 to 64 months. One patient developed a lung metastasis 24 months after surgery, 10 patients have been alive without recurrence. Our study revealed that MGACA is a distinct subset of breast carcinoma, with triple negative phenotype, high grade nuclear and variable morphology. Despite histopathologic and immunohistochemical features usually associated with a poor prognosis, MGACA seems to have a relatively favorable outcome.
PMCID: PMC4203234  PMID: 25337263
Breast carcinoma; microglandular adenosis; matrix-producing carcinoma; triple-negative phenotype; morphology
4.  Primary squamous cell carcinoma of the breast with unusual basal-HER2 phenotype 
Objectives: To report three cases of primary squamous cell carcinoma of the breast with an unusual “basal-HER2” phenotype. Methods: Clinical data were analyzed. Morphological features were observed. Immunohistochemical study for ER, PR, HER2, Ki-67, CK 5/6, CK10/13, CK14, EGFR, P63 and FISH detection of HER2 gene amplification were performed. Results: Three patients were all female with 26, 57 and 66 years old. The tumors were 3 cm, 4 cm and 5 cm in size respectively. Morphologically, all three tumors were pure squamous cell carcinoma and entirely composed metaplastic squamous cells. Two tumors were moderately differentiated and one was poorly differentiated. All three patients were positive for P63 or CK10/13. All three tumors exhibited basal-HER2 phenotype: negative for ER and PR, positive for HER2 protein and HER2 gene amplification, and positive for at least two basal markers. Conclusions: SCC with basal-HER2 phenotype is an extremely rare subset of breast carcinoma. Since it may have worse prognosis than typical basal-like SCC, recognization of this unusual SCC in routine work may have obvious clinical significance.
PMCID: PMC4152088  PMID: 25197398
Squmous cell carcinoma; basal-HER2 phenotype; breast cancer
5.  Gene-environment and protein-degradation signatures characterize genomic and phenotypic diversity in wild Caenorhabditis elegans populations 
BMC Biology  2013;11:93.
Background
Analyzing and understanding the relationship between genotypes and phenotypes is at the heart of genetics. Research on the nematode Caenorhabditis elegans has been instrumental for unraveling genotype-phenotype relations, and has important implications for understanding the biology of mammals, but almost all studies, including forward and reverse genetic screens, are limited by investigations in only one canonical genotype. This hampers the detection and functional analysis of allelic variants, which play a key role in controlling many complex traits. It is therefore essential to explore the full potential of the natural genetic variation and evolutionary context of the genotype-phenotype map in wild C. elegans populations.
Results
We used multiple wild C. elegans populations freshly isolated from local sites to investigate gene sequence polymorphisms and a multitude of phenotypes including the transcriptome, fitness, and behavioral traits. The genotype, transcriptome, and a number of fitness traits showed a direct link with the original site of the strains. The separation between the isolation sites was prevalent on all chromosomes, but chromosome V was the largest contributor to this variation. These results were supported by a differential food preference of the wild isolates for naturally co-existing bacterial species. Comparing polymorphic genes between the populations with a set of genes extracted from 19 different studies on gene expression in C. elegans exposed to biotic and abiotic factors, such as bacteria, osmotic pressure, and temperature, revealed a significant enrichment for genes involved in gene-environment interactions and protein degradation.
Conclusions
We found that wild C. elegans populations are characterized by gene-environment signatures, and we have unlocked a wealth of genotype-phenotype relations for the first time. Studying natural isolates provides a treasure trove of evidence compared with that unearthed by the current research in C. elegans, which covers only a diminutive part of the myriad of genotype-phenotype relations that are present in the wild.
doi:10.1186/1741-7007-11-93
PMCID: PMC3846632  PMID: 23957880
Gene-environment interactions; Genotype-phenotype relations; Wild C. elegans strains; Transcriptomic diversity
6.  The significance of low PU.1 expression in patients with acute promyelocytic leukemia 
Background
Although the importance of the hematopoietic transcription factor PU.1 in acute myeloid leukemia (AML) has been demonstrated, the expression of PU.1 in acute promyelocytic leukemia (APL) patient samples awaits further investigation. The current study used APL patient samples to assess the expression pattern of PU.1 in the initiation and progression of APL.
Findings
We used real-time RT-PCR to compare PU.1 expression between de novo APL patient samples and normal blood specimens, and the results indicated that PU.1 expression was significantly lower in newly diagnosed APL patient samples as compared to normal hematopoietic cells. Further evidence showed a significant inverse correlation between the expression level of PML-RARα and that of PU.1. In addition, we analyzed the correlation between PML-RARα and PU.1 expression in a large population of AML patients retrieved from the expression profiles. The results showed that PU.1 expression was lower in patients with APL than other AML subtypes and there was also a trend towards increasing PU.1 expression from AML-M0 to AML-M5, with the exception of AML-M3 (APL). These observations suggested that PU.1 expression was reduced by PML-RARα in APL patients. Furthermore, we measured PU.1 expression in APL-initiating cells isolated from de novo APL patients by side population cell analysis and found that suppression of PU.1 expression occurred concurrently with PML-RARα expression, indicating the pivotal role of PU.1 in APL initiation.
Conclusion
Our findings provide evidence that low PU.1 expression in APL patients is required for disease initiation and progression.
doi:10.1186/1756-8722-5-22
PMCID: PMC3407792  PMID: 22569057
PML-RARα; PU.1; Acute promyelocytic leukemia
7.  AMD, an Automated Motif Discovery Tool Using Stepwise Refinement of Gapped Consensuses 
PLoS ONE  2011;6(9):e24576.
Motif discovery is essential for deciphering regulatory codes from high throughput genomic data, such as those from ChIP-chip/seq experiments. However, there remains a lack of effective and efficient methods for the identification of long and gapped motifs in many relevant tools reported to date. We describe here an automated tool that allows for de novo discovery of transcription factor binding sites, regardless of whether the motifs are long or short, gapped or contiguous.
doi:10.1371/journal.pone.0024576
PMCID: PMC3171486  PMID: 21931761
8.  Clinicopathological Characteristics and Her-2/neu Status in Chinese Patients with Uterine Papillary Serous Carcinoma 
ISRN Obstetrics and Gynecology  2010;2011:575327.
Objective. To analyze clinico-pathological features of Chinese patients with UPSC, and investigate roles of Her-2/neu protein expression and gene amplification in UPSC prognosis. Methods. Thirty-six patients with UPSC treated in Cancer Hospital of Fudan University from 1996 to 2006 were analysed retrospectively. Chromogenic in situ hybridization (CISH) and immunohistochemistry (IHC) were performed to evaluate Her-2/neu gene amplification and protein expression respectively. Results. The median age was 63 years, and 61% (22/36) were late stages (stage III/IV). The 1-year, 3-year, and 5-year overall survival (OS) was 73.1%, 51.9% and 43.9%, respectively. Advanced stages (P = .0006) and deep myometrial invasion (P = .0138) were significantly associtated with a shorter OS. In 36 cases, 27.8% (10/36) showed 2+ staining and 8.3% (3/36) showed 3+ by IHC. Amplification of the Her-2/neu gene was observed in 11.1% (4/36) cases. The 5-year overall survival rate in Her-2/neu IHC 2 + ∼3+ and 0 ~ 1+ cases was 12.9% and 68.6% respectively. Her-2/neu protein expression 2 + ∼3+ was significantly associated with advanced surgical stage and worse overall survival (P = .03 and P = .0023, resp.). Conclusion. Chinese patients with UPSC showed characteristics of deep myometrial invasion, advanced stages and poor overall survival. Her-2/neu protein overexpression is associated with advanced stage and poor survival outcome.
doi:10.5402/2011/575327
PMCID: PMC3102014  PMID: 21647234
9.  14-3-3ζ Overexpression Defines High Risk for Breast Cancer Recurrence and Promotes Cancer Cell Survival 
Cancer research  2009;69(8):3425-3432.
The ubiquitously expressed 14-3-3 proteins are involved in numerous important cellular functions. The loss of 14-3-3σ is a common event in breast cancer; however, the role of other 14-3-3s in breast cancer is unclear. Recently, we found that 14-3-3ζ overexpression occurs in early stage breast diseases and contributes to transformation of human mammary epithelial cells. Here, we show that 14-3-3ζ overexpression also persisted in invasive ductal carcinoma and contributed to the further progression of breast cancer. To examine the clinical impact of 14-3-3ζ overexpression in advanced stage breast cancer, we performed immunohistochemical analysis of 14-3-3ζ expression in primary breast carcinomas. 14-3-3ζ overexpression occurred in 42% of breast tumors and was determined to be an independent prognostic factor for reduced disease-free survival. 14-3-3ζ overexpression combined with ErbB2 overexpression and positive lymph node status identified a subgroup of patients at high risk for developing distant metastasis. To investigate whether 14-3-3ζ overexpression causally promotes breast cancer progression, we overexpressed 14-3-3ζ by stable transfection or reduced 14-3-3ζ expression by siRNA in cancer cell lines. Increased 14-3-3ζ expression enhanced anchorage independent growth and inhibited stress-induced apoptosis, whereas downregulation of 14-3-3ζ reduced anchorage independent growth and sensitized cells to stress-induced apoptosis via the mitochondrial apoptotic pathway. Transient blockade of 14-3-3ζ expression by siRNA in cancer cells effectively reduced the onset and growth of tumor xenografts in vivo. Therefore, 14-3-3ζ overexpression is a novel molecular marker for disease recurrence in breast cancer patients and may serve as an effective therapeutic target in patients whose tumors overexpress 14-3-3ζ.
doi:10.1158/0008-5472.CAN-08-2765
PMCID: PMC2671640  PMID: 19318578
14-3-3ζ; breast cancer; apoptosis resistance; disease recurrence; prognostic marker

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