Application of fluorescence in situ hybridization in the detection of bladder transitional-cell carcinoma: A multi-center clinical study based on Chinese population.

OBJECTIVE: To evaluate the diagnostic value of fluorescence in situ hybridization (FISH) in bladder cancer. METHODS: We enrolled healthy volunteers and patients who were clinically suspected to have bladder cancer and conducted FISH tests and cytology examinations from August 2007 to December 2008. Receiver operating characteristic (ROC) curve analysis was performed and the area under curve (AUC) values were calculated for both the FISH and urine cytology tests. RESULTS: A cohort of 988 healthy volunteers was enrolled to establish a reference range for the normal population. A total of 4807 patients with hematuria were prospectively, randomly enrolled for the simultaneous analysis of urine cytology, FISH testing, and a final diagnosis as determined by the pathologic findings of a biopsy or a surgically-excised specimen. Overall, the sensitivity of FISH in detecting transitional-cell carcinoma was 82.7%, while that of cytology was 33.4% (p < 0.001). The sensitivity values of FISH for non-muscle invasive and muscle invasive bladder transitional-cell carcinoma were 81.7% and 89.6%, respectively (p = 0.004). The sensitivity values of FISH for low and high grade bladder cancer were 82.6% and 90.1%, respectively (p = 0.002). CONCLUSION: FISH is significantly more sensitive than voided urine cytology for detecting bladder cancer in patients evaluated for gross hematuria at all cancer grades and stages. Higher sensitivity using FISH was obtained in high grade and muscle invasive tumors.

LncRNA LINC00641 predicts prognosis and inhibits bladder cancer progression through miR-197-3p/KLF10/PTEN/PI3K/AKT cascade.

As a new group of important effector molecules involved in multiple cancers, long noncoding RNAs (lncRNAs) have attracted much attention recently. Especially, evidences have indicated lncRNAs might be promising biomarkers and targets for cancer therapy. LINC00641 is a novel lncRNA, whose function remains totally unclear. The aim of our study was to determine the functions of LINC00641 in bladder cancer. We found that LINC00641 expression was significantly down-regulated in bladder cancer tissues. Down-regulation of LINC00641 in patients with bladder cancer predicts poor prognosis. Gain-of-function assays indicated that LINC00641 up-regulation markedly inhibited the proliferation, migration and invasion of bladder cancer cells. Xenograft assay also confirmed that LINC00641 overexpression suppressed bladder cancer growth in vivo. Mechanistically, LINC00641 was demonstrated to interact with miR-197-3p, whose target was KLF10. By up-regulating KLF10 level, LINC00641 suppressed the PTEN/PI3K/AKT pathway, leading to prevention of bladder cancer progression. Taken together, our study illustrated a novel signaling cascade of LINC00641/miR-197-3p/KLF10/PTEN/PI3K/AKT pathway regulating bladder cancer development.

Amplification and protein expression of androgen receptor gene in prostate cancer cells: Fluorescence in situ hybridization analysis.

Prostate cancer (PCa) is the most frequently diagnosed non-skin cancer and the second highest cause of cancer-related mortality in adult males worldwide. PCa is highly dependent upon androgen receptor (AR) signaling for cell proliferation and survival. The AR therefore plays a vital role in the development and function of normal and malignant prostate cells or PCa recurrence. The present study aimed to examine the ubiquity of AR amplification in PCa recurrence, even in the absence of androgen. For this purpose, specimens were collected from 37 patients. The amplification of AR and the number of X chromosomes were determined by two-colored fluorescence in situ hybridization analysis. The automated image analysis was used to determine the protein expression of AR. Clinical characteristics and survival in patients whose tumors showed or did not show AR amplification and in X-chromosome polysomy with PCa recurrence has also been compared. The results showed that >35% of patients (13 specimens) exhibited AR amplification. It was also observed that AR was immunostained more intensely in the tumors with amplified AR compared with those tumors with non-amplified AR. This study demonstrated an influential role of AR in tumor growth and progression even after the deprivation of androgen, as well as showing the potential contribution of AR amplification to AR activation even in the relative absence of androgen.