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Background Urothelial carcinoma (UC) is prevalent worldwide. Dysregulation of cell growth is a critical event of tumorigenesis and has not been assessed systemically in UC. We thus assessed the published transcriptome of urinary bladder urothelial carcinoma (UBUC) and identified insulin-like growth factor-binding protein-5 (IGFBP-5) as the most significantly upregulated gene associated with the regulation of cell growth. Moreover, validated by using public domain data set, IGFBP-5 expression also significantly predicted worse outcome. IGFBP-5 is one of the binding proteins that regulate insulin-like growth factors (IGFs) and its significance has not been comprehensively evaluated in UCs. Methods Using immunohistochemistry, we evaluated the IGFBP-5 expression status and its associations with clinicopathological features and survival in 340 cases of upper urinary tract urothelial carcinoma (UTUC) and 295 cases of UBUC. Western blot analysis was used to evaluate IGFBP-5 protein expression in human urothelial cell (HUC) lines. Results IGFBP-5 overexpression was significantly associated with advanced pT stage ( p<0.001), high histological grade (UTUC, p<0.001; UBUC, p=0.035), lymph node metastasis (UTUC, p=0.006; UBUC, p=0.004), vascular invasion (UTUC, p<0.001; UBUC, p=0.003), perineural invasion (UTUC, p=0.034; UBUC, p=0.021) and frequent mitosis (UTUC, p<0.001; UBUC, p=0.023). IGFBP-5 overexpression also independently predicted poor disease-specific survival and metastasis-free survival in both groups of patients. Western blot analysis showed IGFBP-5 protein as overexpressed in human urothelial cancer cell lines and not in normal urothelial cancer cells. Conclusions IGFBP-5 plays an important role in tumour progression in UC. Its overexpression is associated with advanced tumour stage and conferred poorer clinical outcome. [ABSTRACT FROM AUTHOR]

Background and aim Low expression of cyclindependent kinase 2-associated protein (CDK2AP1) is associated with tumour progression in oral and oesophageal carcinomas, but is not well studied in patients with head and neck cancer and nasopharyngeal carcinoma (NPC). Methods A rabbit anti-human CDK2AP1 polyclonal antibody was prepared. Immunoblotting of CDK2AP1 was examined in three cell lines and immunoexpression was retrospectively assessed in biopsies of 124 consecutive NPC patients without initial distant metastasis and treated with consistent guidelines. Results Higher CDK2AP1 expression level was identified in dysplastic oral keratinocytes, compared with two NPCderived HONE-1 and TW01 cell lines. Low expression of CDK2AP1 (50.8%) was correlated with advanced nodal status (p=0.002) and American Joint Committee on Cancer (AJCC) stage (p=0.004). In multivariate analyses, low CDK2AP1 expression emerged as an independent prognosticator for worse disease-specific survival (DSS; p=0.037) and local recurrence-free survival (LRFS; p=0.042), along with AJCC stage IIIeIV (p=0.034, DSS; p=0.029, LRFS). Conclusions Low CDK2AP1 expression is common and associated with adverse prognosticators, conferring tumour aggressiveness through cycle cycle, cell growth or apoptosis cellular processes. [ABSTRACT FROM AUTHOR]

Backgrounds Urothelial carcinoma of the urinary bladder (UCUB) is prevalent in developed countries. It often shows genetic instability and is associated with amplification (or gain) of various oncogenic genes or suppressive genes. Rsf-1, a subunit of ATP-dependent chromatin-remodelling complexes that mediates ATPasedependent chromatin remodelling, confers tumour aggressiveness in certain carcinomas. The authors evaluate the Rsf-1 gene and expression status and its associations with clinicopathological features and survival in their UCUB collection. Methods Immunohistochemistry was used to assess the Rsf-1 expression profile in 295 UCUB specimens, and was found to correlate with clinicopathological data. Real-time RT-PCR and fluorescence in situ hybridisation were used to detect RSF-1 mRNA expression and gene dosage in 20 independent cases. Western blot analysis was used to evaluate Rsf-1 protein expression in human urothelial cell lines. Results Rsf-1 overexpression was demonstrated in 101 cases (34.2%), and was significantly associated with advanced primary tumour (p<0.001), nodal metastasis (p=0.004), higher histological grades (p=0.001) and frequent mitoses (p<0.001). Moreover, it was predictive in disease-specific survival and metastasis-free survival in both univariate and multivariate analyses (p<0.0001 for both). Although RSF-1 gene amplification can be barely detected, its mRNA expression is significantly enhanced in tumours with higher primary tumour (p=0.041) and positive nodal statuses (p=0.010), respectively. Rsf-1 protein was abundant in invasive urothelial carcinoma cells but was not benign. Conclusions Overexpression of Rsf-1 is associated with higher tumour stage and poorer clinical outcome. The current study by the authors suggests gene amplification-independent mechanisms driving Rsf-1 overexpression during UCUB tumour progression. [ABSTRACT FROM AUTHOR]

Aims Neoadjuvant chemoradiation therapy (CRT) is an increasingly used therapeutic strategy for rectal cancer. Clinically, it remains a major challenge to predict therapeutic response and patient outcome after CRT. Rsf-1 (HBXAP), a novel nuclear protein with histone chaperon function, mediates ATPase-dependent chromatin remodelling and confers tumour aggressiveness and predicts therapeutic response in certain carcinomas. However, the expression of Rsf-1 has never been reported in rectal cancer. This study examined the predictive and prognostic impacts of Rsf-1 expression in patients with rectal cancer following neoadjuvant CRT. Methods Rsf-1 immunoexpression was retrospectively assessed for pre-treatment biopsies of 172 rectal cancer patients without initial distant metastasis. All of them were treated with neoadjuvant CRT followed by surgery. The results were correlated with the clinicopathological features, therapeutic response, tumour regression grade and metastasis-free survival (MeFS), local recurrent-free survival and disease-specific survival. Results Present in 82 cases (47.7%), high-expression of Rsf-1 was associated with advanced pre-treatment tumour status (T3, T4, p=0.020), advanced posttreatment tumour status (T3, T4, p<0.001) and inferior tumour regression grade (p=0.028). Of note, high-expression of Rsf-1 emerged as an adverse prognosticator for diseases-specific survival (p=0.0092) and significantly predicted worse MeFS (p=0.0006). Moreover, high-expression of Rsf-1 also remained prognostic independent for worse MeFS (HR 2.834; p=0.0214). Conclusions High-expression of Rsf-1 is associated with poor therapeutic response and adverse outcome in rectal cancer patients treated with neoadjuvant CRT, which confers tumour aggressiveness and therapeutic resistance through chromatin remodelling and represents a potential prognostic biomarker in rectal cancer. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the expression of epithelial membrane protein-2 (EMP2) protein and its clinicopathological associations in patients with nasopharyngeal carcinoma. Design: Retrospective population-based cohort study. Setting: This study was based on a biobank in Chi-Mei Medical Center (Tainan, Taiwan) from 1993 to 2002. Participants: Biopsies of 124 consecutive nasopharyngeal carcinoma patients without initial distant metastasis and treated with consistent guidelines were assessed. Immunoexpressions of EMP2 were analysed and the outcomes were correlated with clinicopathological features and patient survivals. Primary and secondary outcome measures: Immunoexpressions of EMP2 were analyzed and the outcomes were correlated with clinicopathological features and patient survivals. Results: Loss of EMP2 expression (49.2%) was correlated with advanced primary tumour (p=0.044), nodal status (p=0.045) and the 7th American Joint Committee on Cancer stage (p=0.027). In multivariate analyses, loss of EMP2 expression emerged as an independent prognosticator for worse disease-specific survival (DSS; p=0.015) and local recurrence-free survival (LRFS; p=0.030), along with the American Joint Committee on Cancer stages IIIeIV (p=0.034, DSS; p=0.023, LRFS). Conclusions: Loss of EMP2 expression is common and associated with adverse prognosticators and might confer tumour aggressiveness through hampering its interaction with specific membrane protein(s) and hence the downstream signal transduction pathway(s). [ABSTRACT FROM AUTHOR]

Aims Deregulated chromatin remodelling often leads to aberrant gene expression in cells, thereby implicating tumour development and progression. As a subunit of remodelling and spacing factor complex, Rsf-1 (HBXAP), a novel nuclear protein with histone chaperon function, mediates ATPase-dependent chromatin remodelling and confers tumour aggressiveness in common carcinomas. However, the expression of Rsf-1 has never been reported in nasopharyngeal carcinoma (NPC). This study aimed at evaluating the expression status, associations with clincopathological variables and prognostic implications of Rsf-1 in a well-defined cohort of NPC. Methods Rsf-1 immunoexpression was retrospectively assessed in biopsies of 108 consecutive NPC patients without initial distant metastasis and treated with consistent guidelines. The results were correlated with the clinicopathological features, therapeutic response, local recurrence-free survival (LRFS), distant metastasisfree survival (DMFS) and disease-specific survival (DSS). Results Present in 49 cases (45%), Rsf-1 overexpression was associated with N2,3 status (p=0.016), American Joint Committee on Cancer stage 3, 4 (p=0.004), and incomplete therapeutic response (p=0.041). In multivariate analyses, Rsf-1 overexpression not only emerged as the sole independent adverse prognosticator for LRFS (p=0.0002, RR 5.287) but also independently predicted worse DMFS (p=0.0011, RR 3.185) and DSS (p<0.0001, RR 4.442), along with T3,4 (p=0.0454) and N2,3 (p=0.0319), respectively. Conclusion Rsf-1 overexpression is common and is associated with adverse prognosticators and therapeutic response, which confers tumour aggressiveness through chromatin remodelling, and represents a potential prognostic biomarker in NPC. [ABSTRACT FROM AUTHOR]