Recurrent chromosomal rearrangements have not been well characterized in common carcinomas. We used a bioinformatics approach to discover candidate oncogenic chromosomal aberrations on the basis of outlier gene expression. Two ETS transcription factors, ERG and ETV1, were identified as outliers in prostate cancer. We identified recurrent gene fusions of the 5' untranslated region of TMPRSS2 to ERG or ETV1 in prostate cancer tissues with outlier expression. By using fluorescence in situ hybridization, we demonstrated that 23 of 29 prostate cancer samples harbor rearrangements in ERG or ETV1. Cell line experiments suggest that the androgen-responsive promoter elements of TMPRSS2 mediate the overexpression of ETS family members in prostate cancer. These results have implications in the development of carcinomas and the molecular diagnosis and treatment of prostate cancer.

Prostate cancer is a common and clinically heterogeneous disease with marked variability in progression. The recent identification of gene fusions of the 5 ¶-untranslated region of TMPRSS2 (21q22.3) with the ETS transcription factor family members, either ERG (21q22.2), ETV1 (7p21.2), or ETV4 (17q21), suggests a mechanism for overexpression of the ETS genes in the majority of prostate cancers. In the current study using fluorescence in situ hybridization (FISH), we identified the TMPRSS2:ERG rearrangements in 49.2% of 118 primary prostate cancers and 41.2% of 18 hormone-naive lymph node metastases. The FISH assay detected intronic deletions between ERG and TMPRSS2 resulting in TMPRSS2:ERG fusion in 60.3% (35 of 58) of the primary TMPRSS2:ERG prostate cancers and 42.9% (3 of 7) of the TMPRSS2:ERG hormone-naive lymph node metastases. A significant association was observed between TMPRSS2:ERG rearranged tumors through deletions and higher tumor stage and the presence of metastatic disease involving pelvic lymph nodes. Using 100K oligonucleotide single nucleotide polymorphism arrays, a homogeneous deletion site between ERG and TMPRSS2 on chromosome 21q22.2-3 was identified with two distinct subclasses distinguished by the start point of the deletion at either 38.765 or 38.911 Mb. This study confirms that TMPRSS2:ERG is fused in approximately half of the prostate cancers through deletion of genomic DNA between ERG and TMPRSS2. The deletion as cause of TMPRSS2:ERG fusion is associated with clinical features for prostate cancer progression compared with tumors that lack the TMPRSS2:ERG rearrangement. (Cancer Res 2006; 66(17): 8337-41)

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A repeat Papanicolaou smear combined with a HPV DNA test is a sensitive alternative to colposcopic evaluation for the detection of CIN in women referred for a previous low-grade abnormal Papanicolaou smear. However, because of the low specificity of this approach, it results in only modest cost reductions compared to the more standard triage of performing colposcopy at the first visit.

The purpose of this study was to clarify the outcome of the ratio between metastatic and examined lymph nodes (N ratio) in gastric cancer patients with < or =15 examined lymph nodes after D2 lymphadenectomy. A retrospective study was performed in 906 patients with gastric cancer who had undergone D2 resection. Patients with < or =15 examined lymph nodes (group 1, n = 729) and those with >15 lymph nodes (group 2, n = 177) were analyzed separately. N ratio categories were identified as follows: N ratio 0, 0%; N ratio 1, 1% to 9%; N ratio 2, 10% to 25%; N ratio 3, >25%. Univariate analysis found that both the tumor, node, metastasis system (N staging system) and N ratio system well classified patients with significantly different prognosis. By multivariate analysis, only the N ratio classification was retained as an independent prognostic factor in both group 1 and 2 compared with the N stage system. Furthermore, when patients were divided into four groups according to the number of lymph nodes examined (1 to 3, 4 to 7, 8 to 11, and 12 to 15), the 5-year survival rates remained similar between groups according to the same N ratio (p > .05). Positive N ratio classification is a better prognostic tool compared with N staging system after D2 resection in patients with gastric cancer. It can prevent stage migration and can be used regardless of the examined number of lymph nodes.

Retinal organoids (ROs) derived from human induced pluripotent stem cells (hiPSCs) provide potential opportunities for studying human retinal development and disorders; however, to what extent ROs recapitulate the epigenetic features of human retinal development is unknown. In this study, we systematically profiled chromatin accessibility and transcriptional dynamics over long-term human retinal and RO development. Our results showed that ROs recapitulated the human retinogenesis to a great extent, but divergent chromatin features were also discovered. We further reconstructed the transcriptional regulatory network governing human and RO retinogenesis in vivo. Notably, NFIB and THRA were identified as regulators in human retinal development. The chromatin modifications between developing human and mouse retina were also cross-analyzed. Notably, we revealed an enriched bivalent modification of H3K4me3 and H3K27me3 in human but not in murine retinogenesis, suggesting a more dedicated epigenetic regulation on human genome.

AimTo evaluate the prognostic efficacy of the 7th edition tumor–node–metastasis (TNM) classification compared with the 6th edition in gastric cancer patients.MethodsA total of 1,503 gastric cancer patients undergoing surgical resection were staged using the 6th and 7th edition staging systems. Homogeneity, discriminatory ability, and monotonicity of gradients of the two systems were compared using linear trend χ2, likelihood ratio χ2 statistics, and Akaike information criterion (AIC) calculations.ResultsSignificant differences in 5-year survival rates were observed for the T, N, and M subgroups using the 7th edition system, except for stage N2 and N3 patients in the 6th edition system. There were no significant differences in survival between IB and IIA in the 7th edition system. Patients with stage IV disease due to T4/N3 in the 6th edition system who were downstaged to stage III in the 7th edition system had significantly better survival than those who remained at stage IV. The 7th edition system had higher linear trend and likelihood ratio χ2 scores, and smaller AIC values compared with those for the 6th edition, which represented the optimum prognostic stratification.ConclusionsOur study suggests that the 7th edition system performs better than the 6th edition in several aspects.

BackgroundThis study compared the performance of endoscopic ultrasonography (EUS) and multislice spiral computed tomography (MSCT) in the preoperative staging of gastric cancer.Methodology/Principal FindingsA total of 610 patients participated in this study, all of whom had undergone surgical resection, had confirmed gastric cancer and were evaluated with EUS and MSCT. Tumor staging was evaluated using the Tumor-Node-Metastasis (TNM) staging and Japanese classification. The results from the imaging modalities were compared with the postoperative histopathological outcomes. The overall accuracies of EUS and MSCT for the T staging category were 76.7% and 78.2% (P=0.537), respectively. Stratified analysis revealed that the accuracy of EUS for T1 and T2 staging was significantly higher than that of MSCT (P<0.001 for both) and that the accuracy of MSCT in T3 and T4 staging was significantly higher than that of EUS (P<0.001 and 0.037, respectively). The overall accuracy of MSCT was 67.2% when using the 13th edition Japanese classification, and this percentage was significantly higher than the accuracy of EUS (49.3%) and MSCT (44.6%) when using the 6th edition UICC classification (P<0.001 for both values).Conclusions/SignificanceOur results demonstrated that the overall accuracies of EUS and MSCT for preoperative staging were not significantly different. We suggest that a combination of EUS and MSCT is required for preoperative evaluation of TNM staging.