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Aims Identification of prognostic and predictive biomarkers for breast cancer is essential to better stratify patients for treatment and evaluate patient outcome. AT-rich interactive domain-containing protein 1B ( ARID1B) is implicated in cell proliferation, but its role in tumorigenesis remains unclear. Methods and results Immunohistochemical analysis of ARID1B expression using breast cancer tissue microarrays containing 156 breast invasive ductal carcinoma patient samples and subsequent statistical data analysis based on ARID1B immunoreactivity score were performed to examine the correlation between clinicopathological parameters in breast cancer and ARID1B expression. In-vitro assays were also performed to study the role of ARID1B in cell cycle progression. Univariate analysis revealed that high ARID1B expression is correlated closely with histological grade ( P = 0.045) and size ( P = 0.043) of invasive breast cancer. These findings were confirmed by multivariate analysis. Notably, increased ARID1B expression was frequently detected in the aggressive triple-negative breast cancer subtypes ( P = 0.039) and associated with decreased 5-year disease-free survival rate. Lastly, MDA- MB-231 cells with reduced ARID1B activity displayed a delay in G1 to S phase cell cycle transition and consequently showed a decrease in cell proliferation compared with controls ( P < 0.001). Conclusions ARID1B potentially serves as a valuable prognostic and predictive biomarker as well as a therapeutic target in breast cancer. [ABSTRACT FROM AUTHOR]

The article describes the case of a 38-year-old female patient who was diagnosed with spindle cell sarcoma in her breast and chest wall after receiving radiotherapy for bilateral breast carcinomas. Particular focus is given to the patient's histopathological and immunohistochemistry findings. Also mentioned are myofibroblastic differentiation, undifferentiated sarcoma, and diagnosis of radiation-induced sarcoma.

Aims Y-box binding protein-1 ( YB-1) is known to modulate gene transcription and protein translation, as well as cellular response to drug treatment. The aim of this study is to correlate YB-1 protein expression levels with clinicopathological parameters in intestinal-type gastric cancer tissue samples (as categorized by the Lauren classification) and substantiate the findings with in vitro experimentation. Methods and results Paraffin-embedded samples from 167 patients with intestinal-type gastric cancer were used for the construction of tissue microarrays ( TMAs). TMA slides were immunostained and YB-1 immunoreactivity score was based on the weighted average intensity score. Univariate analysis revealed that YB-1 immunohistochemical expression was correlated significantly with lymph node status ( P = 0.054, borderline significance) and perforation ( P = 0.043). YB-1 expression was also found to be an independent predictor of lymph node spread by multivariate analysis. Furthermore, si RNA-mediated YB-1 gene knockdown in MKN7 gastric cancer cells (which is known to originate from an intestinal-type gastric cancer tissue) inhibited cell migration ( P = 0.0002) and invasion in vitro ( P = 0.0129) significantly. Conclusion YB-1 expression is associated with lymph node spread in intestinal-type gastric cancer and is a potential prognostic biomarker in this subtype of gastric cancer. [ABSTRACT FROM AUTHOR]

Aims Homeoproteins are transcription factors which critically regulate developmental processes. Deregulated expression of homeoproteins is observed in several malignancies, such as breast cancer and rhabdomyosarcoma, and contributes to malignant progression. We aimed to investigate the expression and prognostic importance of Six1 and Pax3 homeoproteins in phyllodes tumours - a group of uncommon biphasic tumours comprising both epithelial and stromal components. Methods and results A total of 272 cases diagnosed from January 2003 to December 2010 were included in this study - 189 (69.5%) benign, 60 (22.1%) borderline and 23 (8.4%) malignant tumours. Immunohistochemistry was performed on tissue microarray sections using antibodies against Six1 and Pax3. Staining H-score was assessed in epithelium and stroma separately, and correlated with tumour grade, clinicopathological parameters and prognosis. Tumour grade was associated positively with stromal cytoplasmic expression ( P < 0.001; P = 0.011) but correlated negatively with epithelial nuclear expression ( P = 0.013; P = 0.007) of both Six1 and Pax3. High stromal cytoplasmic expression of Six1 was associated with metastasis ( P = 0.044) and shorter time to recurrence ( P = 0.056). Pax3 stromal cytoplasmic expression was associated with poorer overall survival ( P = 0.033). Conclusions Six1 and Pax3 expression is correlated with tumour grade, unfavourable clinicopathological parameters and poorer clinical outcome, suggesting that both proteins may play a role in malignant progression. [ABSTRACT FROM AUTHOR]

The literature concerning the subcellular location of Y-box binding protein 1 (YB-1), its abundance in normal and cancer tissues, and its prognostic significance is replete with inconsistencies. An explanation for this could be due in part to the use of different antibodies in immunohistochemical and immunofluorescent labeling of cells and tissues. The inconsistencies could also be due to poor resolution of immunohistochemical data. We analyzed two cohorts of breast tumours for both abundance and subcellular location of YB-1 using three different antibodies; two targeting N-terminal epitopes (AB-a and AB-b) and another (AB-c) targeting a C-terminal epitope. We also investigated stress-induced nuclear translocation of YB-1 in cell culture. We report that both AB-a and AB-c detected increased YB-1 in the cytoplasm of high-grade breast cancers, and in those lacking estrogen and progesterone receptors; however the amount of YB-1 detected by AB-a in these cancers is significantly greater than that detected by AB-c. We confirm our previously published findings that AB-b is also detecting hnRNP A1, and cannot therefore be used to reliably detect YB-1 by immunohistochemistry. We also report that AB-a detected nuclear YB-1 in some tumour tissues and stress treated cells, whereas AB-c did not. To understand this, cancer cell lines were analyzed using native gel electrophoresis, which revealed that the antibodies detect different complexes in which YB-1 is a component. Our data suggest that different YB-1 antibodies show different staining patterns that are determined by the accessibility of epitopes, and this depends on the nature of the YB-1 complexes. It is important therefore to standardize the protocols if YB-1 is to be used reproducibly as a prognostic guide for different cancers. [ABSTRACT FROM AUTHOR]

: PurposeThe expression of inducible nitric oxide synthase (iNOS) and bcl-2 proteins was evaluated and the prognostic significance determined in nasopharyngeal cancer (NPC) patients treated by radiotherapy.: Methods and materialsTissue sections from 55 patients with NPC were assessed for iNOS and bcl-2 protein expression by immunohistochemistry, immunoelectron microscopy, and in situ hybridization before treatment. The markers were correlated with apoptosis (detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay) and clinicopathologic parameters.: ResultsAll NPC sections exhibited positive iNOS and bcl-2 immunoreactivity, with a mean percentage of 6.24% ± 0.58% and 17.09% ± 2.48%, respectively. A significant positive correlation was observed between iNOS expression and the apoptotic index (p < 0.0001, Pearson’s r = 0.8518), and bcl-2 expression correlated inversely with apoptosis (p = 0.0001; Pearson’s r = −0.6170). A significant inverse correlation was found between iNOS and bcl-2 immunoreactivity (p < 0.0001, Pearson’s r = −0.7144). Bcl-2 but not iNOS expression was associated with the stage of the tumor according to the criteria of the American Joint Committee on Cancer (1997) (p < 0.0001). Patients who had recurrence of the tumor and metastasis after radiotherapy had a lower expression of iNOS (p = 0.014 and p = 0.035, respectively), although overall survival was not significantly different statistically. Higher bcl-2 expression was also associated with local tumor recurrence (p = 0.005) but not with metastasis or overall survival.: ConclusionIt appears that iNOS and bcl-2 expression may be potentially useful biomarkers for predicting the outcome of radiotherapy in NPC patients. [Copyright &y& Elsevier]