Clinical significance of protocadherin-8 (PCDH8) promoter methylation in bladder cancer.

OBJECTIVE: To investigate the clinical significance of protocadherin-8 (PCDH8) promoter methylation in bladder cancer. METHODS: Methylation-specific polymerase chain reaction was used to examine the promoter methylation status of PCDH8 in tumour tissue samples obtained from patients with bladder cancer, and in normal bladder epithelial tissue samples obtained from age- and sex-matched control subjects. Methylation status was correlated with demographic, clinical and pathological parameters and disease outcome. RESULTS: PCDH8 promoter methylation was detected in 76/135 (56.3%) patients with bladder cancer and none of 34 (0%) control subjects. Methylation was significantly associated with advanced stage (T2-T4), high grade (G3), tumour recurrence, larger tumour diameter (>3 cm) and nonpapillary morphology. In addition, methylation was associated with significantly shorter survival time and was an independent predictor of overall survival. CONCLUSIONS: PCDH8 promoter methylation is a common occurrence in bladder cancer, and is associated with malignant behaviour and poor prognosis. Determination of PCDH8 promoter methylation status in tumour tissue may assist in the identification of patients who require aggressive postoperative intervention in order to improve prognosis.

The clinical significance of PCDH10 promoter methylation in patients with bladder transitional cell carcinoma.

OBJECTIVE: To investigate the clinical significance of PCDH10 (protocadherin 10) promoter methylation in patients with bladder transitional cell carcinoma (TCC). MATERIALS AND METHODS: 107 samples of bladder TCC and 38 normal bladder epithelial tissues were investigated using methylation-specific PCR, and the relationships between PCDH10 methylation and clinicopathologic features as well as patients' outcome were analyzed. RESULTS: PCDH10 methylation was detected in 63 (58.9%) bladder TCC samples, but no methylation of PCDH10 was found in controls. Moreover, PCDH10 methylation was significantly associated with larger tumor size (p = 0.0074), non-papillary shape (p = 0.0268), tumor relapse (p = 0.0029), high grade (p = 0.0397), advanced stage (p = 0.0004) and poor prognosis (p = 0.0009). In addition, multivariate analysis indicated that PCDH10 methylation is independently associated with poor outcome and may be used as a useful independent prognostic factor (p = 0.0255). CONCLUSIONS: PCDH10 methylation is closely associated with malignancy of bladder TCC and may be used as an independent predictor for patients with bladder TCC.

Downregulation of CDH13 expression promotes invasiveness of bladder transitional cell carcinoma.

OBJECTIVE: To investigate the association of downregulated CDH13 expression with invasiveness of bladder transitional cell carcinoma (TCC). MATERIALS AND METHODS: CDH13 and matrix metalloproteinase-2 (MMP2) expression was detected in 23 normal bladder epithelial tissues and 71 bladder TCC tissues. RNA interference was used to inhibit CDH13 expression in bladder TCC 5637 cells and then analyzed its effects on migration, invasion, adhesion, and proliferation of 5637 cells, as well as MMP2 expression in 5637 cells. RESULTS: The CDH13 expression in bladder TCC tissues was significantly lower than that in normal bladder epithelial tissues. Moreover, the expression of CDH13 from the muscle-invasive group was significantly lower than that from the non-muscle-invasive group. In addition, the MMP2 expression was increased in bladder TCC, especially in muscle-invasive tumors. After the transfection of CDH13 siRNA into 5637 cells, CDH13 expression was significantly decreased, and the migration, invasion, adhesion of 5637 cells, as well as MMP2 expression in 5637 cells was significantly promoted compared with blank and negative controls. CONCLUSIONS: Downregulated expression of CDH13 is associated with increased invasion of bladder TCC, and may be due to the enhancement of cell-extracellular matrix adhesion and increased MMP2 expression.

[Histological characteristics of the prostate in men who receive re-TURP for benign prostatic hyperplasia and their clinical significance].

OBJECTIVE: To investigate the pathohistological characteristics of the prostate tissues in patients who receive a second TURP and to evaluate their clinical significance. METHODS: We collected surgical specimens from 50 cases of TURP (the control group) and another 50 cases of re-TURP (the re-TURP group), detected the expressions of CD34, vascular endothelial growth factor (VEGF) and androgen receptor (AR) in the prostate tissues by immunohistochemistry (S-P), and determined microvessel density (MVD) and the expressions of VEGF and AR. We performed statistical analyses on the results obtained from the specimens of the control group as well as from those of the first and second operations of the re-TURP group. RESULTS: VEGF and AR expressed in all the specimens. The expressions of VEGF and AR and MVD were significantly higher in the re-TURP group than in the controls (P < 0.05), but showed no significant differences between the first and second operations in the re-TURP group (P > 0.05). Positive correlations were found between the expressions of AR and VEGF, VEGF and MVD, and AR and MVD (r = 0.650, 0.705 and 0.525, P < 0.05). CONCLUSION: Increased AR, VEGF and MVD in the prostatic tissues may be one of the important causes of recurrence of BPH after TURP, and could be considered as the risk factors for postoperative recurrence and targeted indicators for preventive measures.

Polymorphisms of GSTM1 and CYP1A1 genes and their genetic susceptibility to prostate cancer in Chinese men.

BACKGROUND: Variation in prostate cancer incidence between different racial groups has been well documented, for which genetic polymorphisms are hypothesized to be an explanation. We evaluated the association between polymorphisms in the cytochrome P-450 CYP1A1 (CYP1A1) and glutathione S-transferase M1 (GSTM1) genes and genetic susceptibility to prostate cancer in Chinese men. METHODS: Two hundred and eight prostate cancer patients and 230 age matched controls were enrolled in this study. All DNA samples from peripheral blood lymphocytes were genotyped for common genetic polymorphisms of the CYP1A1 and GSTM1 genes using the oligonucleotide microarray (DNA chip) technique and the polymorphism results confirmed by sequencing. The different polymorphisms in prostate cancer patients were also analyzed according to age at diagnosis, prostate specific antigen level, cancer stage and grade (Gleason score). RESULTS: The prevalence of the GSTM1 (0/0) genotype was significantly higher in prostate cancer patients (58.2%) than in controls (41.7%, P<0.05). Further analysis demonstrated that the prostate cancer patients with a GSTM1 (0/0) genotype were younger than those with the GSTM1 (+/+) genotype (P=0.024). No significant differences in the frequency distributions of CYP1A1 polymorphisms were observed between prostate cancer patients and controls. CONCLUSION: GSTM1 (0/0) gene polymorphism may be linked to prostate cancer risk and early age of onset in Chinese.

[Polymorphism of metabolic gene and genetic susceptibility to prostate cancer].

OBJECTIVE: To study the possible relationship between the single nucleotide polymorphism (SNP) of cytochrome P-450 CYP1A1 (CYP1A1) m1, m2 and GSTM1 [null] genotype and genetic susceptibility to prostate cancer (PC). METHODS: Eighty-three PC patients and 115 age-matched healthy controls were enrolled in this study. All DNA samples from peripheral blood were genotyped for genetic polymorphisms of CYP1A1 and GSTM1 genes by genechip technique. RESULTS: There was a significant difference in the frequency of GSTM1 [null] genotype in PC cases (57.8%) compared to healthy controls (41.7%) (chi(2) = 4.99, P = 0.025). Individuals with the GSTM1 [null] genotype demonstrated increased risk (OR = 1.9, 95% CI = 1.10-1.34). The frequency of the GSTM1 [null] genotype was also higher in patients with advanced stage or high grade disease. There were no significant differences in the frequent distribution of two locate of CYP1A1 polymorphisms between prostate cancer patients and healthy controls (P > 0.05). CONCLUSIONS: GSTM1 [null] genotype may be linked to prostate cancer risk in Chinese population. GSTM1 [null] genotype was also related to the stage and grade, which may be helpful in determining the risk of locally disease and advanced PC.