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Objectives: To investigate the significance of dedicated central pathologic review for Gleason score (GS) correlation between the biopsy and radical prostatectomy (RP) specimens and the prediction of high-grade Gleason patterns. A discrepancy in the GS between the biopsy and RP specimens has been reported. Methods: The Clinicopathological Research Group for Localized Prostate Cancer disease registry collated the data from 1629 patients who had undergone RP from 1997 to 2005. All biopsy and RP specimens were retrospectively re-evaluated by 2 central uropathologists according to the International Society of Urological Pathology consensus. The GS correlation between the biopsy and RP specimens and the presence of high-grade Gleason patterns (4 or 5) were recorded. The GS was categorized into 5 groups (2-4, 5-6, 3 + 4, 4 + 3, and 8-10). Results: Central review significantly increased the exact concordance rate and decreased the undergrading and overgrading rates between the biopsy and RP specimens compared with local review (P < .05 for all). In each GS or prostate-specific antigen group, the central review biopsy GS had a significantly greater exact concordance rate with the RP specimen GS compared with the local review biopsy GS (P < .05 for all). Regarding high-grade Gleason patterns in the RP specimens, central review showed significantly greater sensitivity, positive predictive value, and negative predictive value than local review (P < .05 for all). Conclusions: We have demonstrated that central review using the International Society of Urological Pathology consensus improves the GS correlation and better predicts high-grade Gleason patterns compared with local review. We recommend central pathologic review by dedicated uropathologists for multi-institutional studies using data from prostate biopsy and RP specimens. [ABSTRACT FROM AUTHOR]

Background: The correlation between fine surface patterns of gastric mucosal lesions and early gastric cancer is not sufficiently clear. Objective: To evaluate the efficacy of surface pattern classification by enhanced-magnification endoscopy (EME) for identifying early gastric cancers. Design: Observational study. Setting: All procedures were performed at Mie University Hospital. Patients: A total of 380 consecutive patients who underwent EGD by using magnification endoscopy. Among these subjects were found 250 newly detected lesions suspected of being gastric cancer. Methods: Conventional magnification endoscopy (CME), magnification chromoendoscopy (MCE), and EME were performed, and surface patterns of lesions were classified into 5 types: type I, small round pits of uniform size and shape; type II, slit-like pits; type III, gyrus and villous patterns; type IV, irregular arrangement and size; and type V, destructive pattern. Biopsy specimens were obtained from all lesions. Main Outcome Measurements: Correlation between surface pattern classification by EME and histopathologic findings of early gastric cancer. Results: Surface patterns were evident by CME/MCE in only 66.4% (166/250) of lesions but in 100% (250/250) of lesions by EME. Classification by EME was as follows: type I, 52 lesions; type II, 12; type III, 146; type IV, 32; and type V, 8. By histopathologic examination, 16 early gastric cancers were detected between type IV or V lesions. Thus, classification of types IV-V strongly correlated with the presence of gastric cancer (sensitivity 100%, specificity 89.7%). Limitations: Single-center study. Conclusions: Surface pattern classification by EME may be useful for identifying early gastric cancers. [Copyright &y& Elsevier]

: ObjectivesTo determine the percent area density of epithelial and stromal components in the development of prostatic hyperplasia in spontaneously hypertensive (SH) rats.: MethodsThe ventral lobes of prostates obtained from male SH rats and their normotensive counterparts, Wistar Kyoto (WKY) rats, were examined histopathologically at 15, 29, 40, and 54 weeks of age (5 SH and WKY rats each at each age group). The degree of prostatic hyperplasia was evaluated with a score-chart protocol, histoscore. The percent area density of epithelium and stroma of the ventral prostate were determined using a computerized image analysis system.: ResultsDefinite lesions of hyperplastic changes were demonstrated in the ventral prostate of SH rats from 15 to 54 weeks. In comparison with WKY rats, SH rats showed a significantly increased degree of prostatic hyperplasia as reflected by the histoscore values. Furthermore, the histoscore of the ventral prostate of SH rats increased with age (from 21.7 ± 0.7 at 15 weeks to 26.1 ± 0.4 at 54 weeks). The percent area density of epithelium and stroma were significantly increased in SH rats, and the ratio of stroma to epithelium ranged from 1:2.94 to 1:3.50 in SH rats but was maintained at 1:1.15 to 1:1.19 in WKY rats during the observation period.: ConclusionsThe hyperplastic changes of the ventral prostate may develop with advancing age in SH rats. The development of prostatic hyperplasia may result from both epithelial and stromal proliferation and may be predominantly expressed as a glandular type in SH rats. [Copyright &y& Elsevier]

Objective: To distinguish good candidates for watchful waiting from those who need immediate treatment in localized prostate cancer.Methods: Prostate specific antigen (PSA)-doubling time (DT) was calculated by a log-linear regression model for 78 patients with clinically localized prostate cancer (T1c: 47, T2a: 6, T2b: 21, and T3: 4) under surveillance. Median observation period was 37.5 months. The first 1-year PSA-DT was compared with the overall PSA-DT in 41 patients who had been under surveillance for more than 3 years.Results: There was significant difference in the PSA-DT distribution between a pooled group of T1c and T2a and a group of T2b and T3 patients (median 58.8 versus 33.3 months, P=0.0052). A combination of three parameters consisting of initial PSA level less than 10 ng/ml, WHO grade 1, one or two positive core per six to eight systematic biopsy cores with 50% or less cancer involvement significantly correlated with PSA-DT distribution in the T1c plus T2a group (P=0.0034). The first year assessment of PSA-DT was identical to the overall assessment in 48.8%, 2 years or more in 36.6%, while it was 2 years or less (possibly over-estimated) in 14.6%.Conclusion: PSA-DT can be predictable to some extent with the initial PSA level and biopsy features in early stage prostate cancers. Prospective study is needed to clarify whether temporary observation together with PSA-DT estimation is a safe strategy and is complementary to clinico-pathological parameters at diagnosis. [Copyright &y& Elsevier]

Abstract: Objectives: To investigate the presence of manserin in human prostate cancers and to correlate manserin expression with pathologic outcomes and progression-free survival. Methods: Eighty-seven patients with recent prostate cancer were classified into 4 groups based on Gleason score, and manserin immunohistochemistry was correlated with Gleason sum grade. To investigate the validity of manserin as a prognostic factor, the Cox proportional hazards regression model was performed on 48 patients in our cohort with T3 or T4 prostate cancer who were initially treated with androgen deprivation therapy. Results: The manserin-positive rates of patients with Gleason sums of 6, 7, 8, and ≥9 were 0%, 20.0%, 35.0%, and 48.1%, respectively. Manserin-positive rates were positively correlated with Gleason sums (P = 0.0001). Median times to cancer progression in groups with (n = 8) and without (n = 40) manserin expression were 8 months and 28 months, respectively (P = 0.01). Univariate Cox analysis revealed that manserin expression, clinical stage T4, and high Gleason sum were significantly associated with progression. Multivariate analysis revealed that only 2 factors, manserin expression (hazard ratio (HR) 4.99, P = 0.01) and clinical stage T4 (HR 4.77, P = 0.03), were independent risk factors for progression. Conclusions: This is the first report of manserin expression in human prostate cancers. Manserin may serve as a marker of prostate cancer progression. [Copyright &y& Elsevier]

Abstract: Combination vaccines of the NY-ESO-1 protein complexed with cholesteryl pullulan (CHP), CHP-NY-ESO-1, and the truncated 146HER2 protein with CHP, CHP-HER2, were subcutaneously administered with the immuno-adjuvant OK-432 to eight esophageal cancer patients. Vaccination was well-tolerated. NY-ESO-1- and HER2-specific antibody responses were analyzed using the patients’ sera and samples from previous single CHP-NY-ESO-1 or CHP-HER2 vaccine trial. The responses to NY-ESO-1 in the combination vaccine study were comparable to the single vaccine. For responses to HER2, there were fewer antibody responses in the combination vaccines. Although there were marked individual variations in the antibody responses to the NY-ESO-1 and HER2 antigens, the reaction patterns to these antigens were comparable within each patient. Antibodies to OK-432 were not augmented. Protein cancer vaccines targeting multiple antigens are feasible. [Copyright &y& Elsevier]

Summary: Methylthioadenosine phosphorylase (MTAP) is involved in the metabolism of purines and converts methylthioadenosine (MTA) to adenine. It is abundant in all normal tissues but is deficient in various tumors. Here, we investigated MTAP deficiency in clinical samples of lung cancer using immunohistochemistry (IHC), and compared these results with those obtained by real-time PCR. Seventy-five samples were obtained from patients who underwent operations for non-small cell lung cancer (NSCLC). MTAP genetic analysis, using real-time PCR, and IHC were carried out on the samples. Methylation-specific primers were used to analyze methylation of the MTAP promoter, using DNA treated with sodium bisulfite. Sixty-nine of 75 samples were compared using both IHC and real-time PCR. The IHC results were consistent with those of real-time PCR in 56 samples. Of 62 positive samples tested by real-time PCR, only 49 (79%) were MTAP-positive by IHC. Seven samples were MTAP-negative by real-time PCR and IHC. In 13 samples of PCR (+) and IHC (−), six samples showed that the promoter region of MTAP was methylated. IHC is an accurate and useful diagnostic method for detecting MTAP deficiency in NSCLC, and the frequency of MTAP deficiency was found to be relatively high. The metabolic alterations diagnosed by IHC could be exploited for selective chemotherapy. [Copyright &y& Elsevier]