We retrospectively studied 19 cases of nasal NK/T-cell lymphoma for various potential prognostic factors and performed real-time quantitative polymerase chain reaction for Epstein-Barr virus (EBV) viral load in tumor tissue. Patients with a low EBV viral load (<1 copy per cell) more frequently survived for more than 2 years compared with patients with a high EBV viral load (>/=1 copies/cell) (7/7 vs 3/9; P = .014; Fisher exact test). Furthermore, the patients with low EBV viral loads had a better overall survival than patients with high viral loads (50% accumulative survival: not reached vs 4-5 months; Kaplan-Meier survival analysis; P = .049). In contrast, the overall survival of the patients did not correlate with the extent of lesion, age, stage, necrosis, histologic subtypes, CD56 expression, or angiocentric or angiodestructive growth pattern. Our findings suggest that the EBV viral load in tumor tissues is a useful indicator for predicting outcome of nasal NK/T-cell lymphoma.

No abstract

Urothelial carcinoma (UC) carcinogenesis has been hypothesized to occur through epigenetic repression of tumor-suppressor genes (TSGs). By quantitative real-time polymerase chain reaction array, we found that one potential TSG, angiopoietin-like 4 (ANGPTL4), was expressed at very low levels in all bladder cancer cell lines we examined. Previous studies had demonstrated that ANGPTL4 is highly expressed in some cancers, but downregulated, by DNA methylation, in others. Consequently, owing to these seemingly conflicting functions in distinct cancers, the precise role of ANGPTL4 in the etiology of UC remains unclear. In this study, using methylation-specific PCR and bisulfite pyrosequencing, we show that ANGPTL4 is transcriptionally repressed by DNA methylation in UC cell lines and primary tumor samples, as compared with adjacent noncancerous bladder epithelium. Functional studies further demonstrated that ectopic expression of ANGPTL4 potently suppressed UC cell proliferation, monolayer colony formation in vitro, and invasion, migration, and xenograft formation in vivo. Surprisingly, circulating ANGPTL4 was significantly higher in plasma samples from UC patients than normal control, suggesting it might be secreted from other cell types. Interestingly, our data also indicated that exogenous cANGPTL4 could promote cell proliferation and cell migration via activation of signaling through the Erk/focal adhesion kinase axis. We further confirmed that mouse xenograft tumor growth could be promoted by administration of exogenous cANGPTL4. Finally, immunohistochemistry demonstrated that ANGPTL4 was downregulated in tumor cells but overexpressed in tumor adjacent stromal tissues of muscle-invasive UC tissue samples. In conclusion, our data support dual roles for ANGPTL4 in UC progression, either as a tumor suppressor or oncogene, in response to microenvironmental context.

No abstract

Background. Survivin is a member of the inhibitors of apoptosis protein family that plays an important role in carcinogenesis. Here, we examined the association between survivin expression and clinical outcome in urothelial carcinoma of the bladder (UCB). Methods. A total of 56 histopathologically confirmed UCB patients were recruited from the Department of Urology of Chiayi Christian Hospital from August 2007 to May 2009. Immunohistochemistry (IHC) was used to detect the survivin expression in tumor tissues. The –31 C/G polymorphism in survivin promoter region was determined by polymerase chain reaction-restricted fragment length polymorphism. Results. The frequency of high survivin expression was significantly higher in muscle-invasive tumors (66.6%) than in non-muscle-invasive tumors (34.2%) (P = 0.042) and in poorly differentiated (85.7%) tumors than in moderately differentiated tumors (30.8%) (P = 0.0014). The higher frequency of risk genotypes (C/C and C/G) was found in the median (72.7%) and high (68.0%) survivin expression groups. The multivariate analysis showed that a high survivin expression level was a potential predictive biomarker of poor overall survival (P = 0.02). Conclusion. Our results suggest that the high survivin expression was associated with tumor stage and grade and may present a predictive marker of overall survival in UCB.