The utility of apical anterior horn biopsies in prostate cancer detection.

We sought to determine the utility of adding apical anterior horn biopsies to systematic prostate sampling regimens in detecting cancer in men with measured prostate volume < or =50 cc. We reviewed the biopsy data of consecutive men referred for an abnormal digital rectal exam or PSA elevation > or =4.0 ng/mL. All of these patients underwent lesion directed biopsy as well as a systematic 12-core biopsy regimen consisting of the standard sextant, bilateral lateral mid- and lateral base-sites, and bilateral apical anterior horn sites. Overall cancer detection and unique cancer detection rates were calculated for each of the 12 sites, stratified by race, age, PSA, and findings on digital rectal exam. In addition, cancer detection rates of various biopsy schemes were calculated and compared. There were 255 men undergoing biopsy who had calculated prostate volume < or =50 cc, and the prostate cancer detection rate was 47%. The overall cancer detection rate of apical anterior horn biopsies ranged between 29% and 56%. The utility of these biopsies was greatest in men with normal rectal exam and PSA <10 ng/mL, with unique cancer detection rates of 6% and 4%, respectively. Including the apical anterior horn biopsies in an 8-biopsy scheme (anterior, apex, lateral mid, lateral base) yielded cancer detection rates greater than 91% in all subgroups that were not statistically different from extended 10- and 12-core biopsy regimens. Apical anterior horn prostate biopsies target cancers that are potentially in the anterior region of the prostate, a region under-sampled using traditional schemes. The use of these biopsies as part of an 8-core biopsy pattern provides high cancer detection in all groups of patients and may represent a new standard.

CpG hypermethylation of promoter region and inactivation of E-cadherin gene in human bladder cancer.

Several studies have shown that E-cadherin expression is lost during malignant transformation. We hypothesized that CpG methylation in the promoter region may inactivate the expression of the E-cadherin gene in human bladder cancer. Normal and bladder cancer samples from 51 patients were compared in terms of E-cadherin gene expression and methylation status by immunohistochemistry, methylation-specific polymerase chain reaction (MSP), and bisulfite genome-sequencing techniques. Ten different CpG sites (nt 863, 865, 873, 879, 887, 892, 901, 918, 920, and 940) in the promoter region were studied. Thirty-five of 51 (69%) bladder cancer samples lacked E-cadherin expression, whereas only six of 51 (12%) normal bladder samples lacked E-cadherin immunoreactivity. MSP analysis of bladder cancer samples suggested that 43 of 51 (84%) showed methylation of the promoter region, whereas only 12 of 51 (24%) normal bladder samples showed hypermethylation. Sodium bisulfite genome-sequencing analysis revealed that of 10 CpG sites, two sites (nt 892 and nt 940) showed 100% methylation in all the cancer samples analyzed. Other CpG sites were partially methylated (47-91%). Normal tissue showed only 12% methylation (range, 1-33%) on various CpG sites. Also supporting these data, E-cadherin-negative bladder cancer cell lines restored expression of the E-cadherin gene after treatment with the demethylating agent 5-aza-2'-deoxycytidine. The present study showed that CpG hypermethylation was an important mechanism of E-cadherin gene inactivation in bladder cancer and also that specific CpG sites consistently presented higher methylation levels than others. These findings may provide a better strategy for the diagnosis and management of bladder cancer.