Publications (2)5.89 Total impact
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Article: Landscape of chromosome number changes in prostate cancer progression.
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ABSTRACT: PURPOSE: Both genetic instability resulting in aneuploidy and increased proliferative activity are common features of tumor development and progression. Cytometric evaluation of tumor ploidy status was recently suggested as a prognostic marker. However, in prostate cancer (PCa), a chromosome-specific evaluation is lacking. With the present study, we sought to identify distinct chromosomal changes to complement cytometric results concerning the diagnosis and prognosis of PCa patients. METHODS: We assessed a cohort of 428 PCa specimens (186 localized PCa, 75 lymph node metastasized PCa, 125 lymph node metastases, 42 hormone-refractory distant metastases) for numerical alterations of all 24 chromosomes by using fluorescence in situ hybridization (FISH). Conducting immunohistochemistry with phosphorylated histone H3 (PHH3) and Ki-67, we quantified the proliferation rate. FISH results were fit in a linear model and tested for predictive power. RESULTS: As expected, we observed a significant increase in aneuploidy with advancing tumor stage. Similarly, an increased expression of the mitotic marker PHH3 was significantly associated with aneuploidy and higher pT-stage. We found aneusomy of chromosomes 4, 6, 20, and X to be indicative of lymph node metastasized PCa. However, with an AUC of 65 %, this set of chromosomal changes was poorly suited to distinguish non-metastasized and lymph node metastasized primary tumors. CONCLUSION: Our results provide thorough insight into the so far incompletely elucidated chromosomal landscape of PCa. While overall ploidy status and PHH3 expression in primary tumors indicate advanced disease, a FISH-based test for distinct alterations does not seem to be beneficial for diagnostic or prognostic decisions.World Journal of Urology 03/2013; · 2.41 Impact Factor -
Article: Improved method of detecting the ERG gene rearrangement in prostate cancer using combined dual-color chromogenic and silver in situ hybridization.
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ABSTRACT: The recently detected TMPRSS2-ERG fusion gene was revealed as a recurrent and prevalent prostate cancer (PCa)-specific event, potentially qualifying it for clinical use. To detect this alteration, fluorescence in situ hybridization (FISH) is the method of choice. However, FISH has some disadvantages for widespread adoption in clinical practice. Subsequently, chromogenic in situ hybridization, which uses organic chromogens, and enzymatic metallography silver in situ hybridization have emerged as promising bright-field alternatives. Compared with chromogenic in situ hybridization, silver in situ hybridization signals are very distinct and superior with regard to signal clarity and resolution, but the method excludes multicolor protocols. Based on the ERG break-apart FISH assay, we established a dual-color ERG break-apart assay using combined chromogenic in situ hybridization and silver in situ hybridization (CS-ISH) and compared these results with those obtained by FISH. We assessed 178 PCa and 10 benign specimens for their ERG rearrangement status by applying dual-color FISH and CS-ISH ERG break-apart assays to consecutive sections. We observed a highly significant concordance (97.7%) between FISH- and CS-ISH-based results (Pearson's correlation coefficient = 0.955, P < 0.001). Our findings demonstrate that the ERG rearrangement status can reliably be assessed by CS-ISH. Further, the CS-ISH technique combines the accuracy and precision of FISH with the ease of bright-field microscopy. This tool allows a much broader spectrum of applications in which to study the biological role and clinical use of ERG rearrangements in PCa.The Journal of molecular diagnostics: JMD 05/2012; 14(4):322-7. · 3.48 Impact Factor
