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Erschienen in: Der Urologe 4/2014

01.04.2014 | Leitthema

Prognostische und prädiktive molekulare Marker urologischer Tumoren

verfasst von: A. Hartmann, T. Schlomm, S. Bertz, J. Heinzelmann, S. Hölters, R. Simon, R. Stoehr, Prof. Dr. K. Junker

Erschienen in: Die Urologie | Ausgabe 4/2014

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Zusammenfassung

Molekulare Prognosefaktoren und genetische Veränderungen als prädiktive Marker für die Wirksamkeit spezifischer Target-Therapien sind bei vielen malignen Tumoren in den klinischen Alltag eingezogen. Bei urologischen Tumoren wurden zwar in den letzten Jahren zahlreiche molekulare Marker identifiziert. Diese werden heute jedoch noch nicht in der Klinik genutzt. Beim Prostatakarzinom haben moderne Sequenzierverfahren ein immer differenzierteres Bild der molekularen Grundlagen geliefert. Es zeichnet sich ab, dass durch die Kombination klassischer histologischer und validierter molekularer Marker Verbesserungen in der Prognoseabschätzung zu erwarten sind, die zukünftig für mehr Patienten eine „Active Surveillance“ als realistische Therapieoption erscheinen lassen. Beim Urothelkarzinom sind neben klassischen histopathologischen Faktoren v. a. die Proliferation des Tumors, der Mutationsstatus für proliferationsfördernde Onkogene und Veränderungen in Genen, die zur Invasion und Metastasierung führen, von wesentlicher Bedeutung. Zusätzlich konnten Genexpressionsprofile identifiziert werden, die aggressive, metastasierende von nicht-metastasierenden Tumoren unterscheidet und somit in Zukunft Patienten selektieren könnten, die eine systemische perioperative Therapie benötigen. Für die Nierenzellkarzinome wurden eine ganze Reihe molekularer Marker identifiziert, die eine Korrelation mit der Prognose im Sinne der Metastasierung und dem Überleben der Patienten zeigen. Ein Teil dieser Marker konnte auch als unabhängige Prognoseparameter bestätigt werden. In Zukunft scheint damit eine Selektion von Patienten, die ein erhöhtes Metastasierungsrisiko bei primär organbegrenzten Tumoren haben und einer adjuvanten systemischen Therapie zugeführt werden sollten, möglich.
Literatur
1.
Zurück zum Zitat Alqurashi N, Hashimi SM, Wei MQ (2013) Chemical Inhibitors and microRNAs (miRNA) Targeting the Mammalian Target of Rapamycin (mTOR) pathway: potential for novel anticancer therapeutics. Int J Mol Sci 14:3874–3900PubMedCentralPubMedCrossRef Alqurashi N, Hashimi SM, Wei MQ (2013) Chemical Inhibitors and microRNAs (miRNA) Targeting the Mammalian Target of Rapamycin (mTOR) pathway: potential for novel anticancer therapeutics. Int J Mol Sci 14:3874–3900PubMedCentralPubMedCrossRef
2.
Zurück zum Zitat Als AB, Dyrskjot L, Maase H von der et al (2007) Emmprin and survivin predict response and survival following cisplatin-containing chemotherapy in patients with advanced bladder cancer. Clin Cancer Res 13:4407–4414PubMedCrossRef Als AB, Dyrskjot L, Maase H von der et al (2007) Emmprin and survivin predict response and survival following cisplatin-containing chemotherapy in patients with advanced bladder cancer. Clin Cancer Res 13:4407–4414PubMedCrossRef
3.
Zurück zum Zitat Balbas-Martinez C, Sagrera A, Carrillo-de-Santa-Pau E et al (2013) Recurrent inactivation of STAG2 in bladder cancer is not associated with aneuploidy. Nat Genet 45:1464–1469PubMedCrossRef Balbas-Martinez C, Sagrera A, Carrillo-de-Santa-Pau E et al (2013) Recurrent inactivation of STAG2 in bladder cancer is not associated with aneuploidy. Nat Genet 45:1464–1469PubMedCrossRef
4.
Zurück zum Zitat Barbieri CE, Baca SC, Lawrence MS et al (2012) Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer. Nat Genet 44:685–689PubMedCentralPubMedCrossRef Barbieri CE, Baca SC, Lawrence MS et al (2012) Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer. Nat Genet 44:685–689PubMedCentralPubMedCrossRef
5.
Zurück zum Zitat Berger MF, Lawrence MS, Demichelis F et al (2010) The genomic complexity of primary human prostate cancer. Nature 470:214–220CrossRef Berger MF, Lawrence MS, Demichelis F et al (2010) The genomic complexity of primary human prostate cancer. Nature 470:214–220CrossRef
6.
Zurück zum Zitat Burger M, Aa MN van der, Oers JM van et al (2008) Prediction of progression of non-muscle-invasive bladder cancer by WHO 1973 and 2004 grading and by FGFR3 mutation status: a prospective study. Eur Urol 54:835–843PubMedCrossRef Burger M, Aa MN van der, Oers JM van et al (2008) Prediction of progression of non-muscle-invasive bladder cancer by WHO 1973 and 2004 grading and by FGFR3 mutation status: a prospective study. Eur Urol 54:835–843PubMedCrossRef
7.
Zurück zum Zitat Burkhardt L, Fuchs S, Krohn A et al (2013) CHD1 Is a 5q21 tumor suppressor required for ERG rearrangement in prostate cancer. Cancer Res 73:2795–2805PubMedCrossRef Burkhardt L, Fuchs S, Krohn A et al (2013) CHD1 Is a 5q21 tumor suppressor required for ERG rearrangement in prostate cancer. Cancer Res 73:2795–2805PubMedCrossRef
8.
Zurück zum Zitat Cancer Genome Atlas Research N (2013) Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature 499:43–49CrossRef Cancer Genome Atlas Research N (2013) Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature 499:43–49CrossRef
9.
Zurück zum Zitat Cho D, Signoretti S, Dabora S et al (2007) Potential histologic and molecular predictors of response to temsirolimus in patients with advanced renal cell carcinoma. Clin Genitourin Cancer 5:379–385PubMedCrossRef Cho D, Signoretti S, Dabora S et al (2007) Potential histologic and molecular predictors of response to temsirolimus in patients with advanced renal cell carcinoma. Clin Genitourin Cancer 5:379–385PubMedCrossRef
10.
Zurück zum Zitat Choi W, Porten S, Kim S et al (2014) Identification of distinct Basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy. Cancer Cell 25:152–165PubMedCrossRef Choi W, Porten S, Kim S et al (2014) Identification of distinct Basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy. Cancer Cell 25:152–165PubMedCrossRef
11.
Zurück zum Zitat Choudhury A, Nelson LD, Teo MT et al (2010) MRE11 expression is predictive of cause-specific survival following radical radiotherapy for muscle-invasive bladder cancer. Cancer Res 70:7017–7026PubMedCentralPubMedCrossRef Choudhury A, Nelson LD, Teo MT et al (2010) MRE11 expression is predictive of cause-specific survival following radical radiotherapy for muscle-invasive bladder cancer. Cancer Res 70:7017–7026PubMedCentralPubMedCrossRef
12.
Zurück zum Zitat Cuzick J, Berney DM, Fisher G et al (2012) Prognostic value of a cell cycle progression signature for prostate cancer death in a conservatively managed needle biopsy cohort. Br J Cancer 106:1095–1099PubMedCentralPubMedCrossRef Cuzick J, Berney DM, Fisher G et al (2012) Prognostic value of a cell cycle progression signature for prostate cancer death in a conservatively managed needle biopsy cohort. Br J Cancer 106:1095–1099PubMedCentralPubMedCrossRef
13.
Zurück zum Zitat Damrauer JS, Hoadley KA, Chism DD et al (2014) Intrinsic subtypes of high-grade bladder cancer reflect the hallmarks of breast cancer biology. Proc Natl Acad Sci U S A 111:3110–3115PubMedCrossRef Damrauer JS, Hoadley KA, Chism DD et al (2014) Intrinsic subtypes of high-grade bladder cancer reflect the hallmarks of breast cancer biology. Proc Natl Acad Sci U S A 111:3110–3115PubMedCrossRef
14.
Zurück zum Zitat Martino E di, Tomlinson DC, Knowles MA (2012) A decade of FGF receptor research in bladder cancer: past, present, and future challenges. Adv Urol 2012:429213PubMedCentralPubMedCrossRef Martino E di, Tomlinson DC, Knowles MA (2012) A decade of FGF receptor research in bladder cancer: past, present, and future challenges. Adv Urol 2012:429213PubMedCentralPubMedCrossRef
15.
Zurück zum Zitat Dyrskjot L, Thykjaer T, Kruhoffer M et al (2003) Identifying distinct classes of bladder carcinoma using microarrays. Nat Genet 33:90–96PubMedCrossRef Dyrskjot L, Thykjaer T, Kruhoffer M et al (2003) Identifying distinct classes of bladder carcinoma using microarrays. Nat Genet 33:90–96PubMedCrossRef
16.
Zurück zum Zitat Dyrskjot L, Zieger K, Real FX et al (2007) Gene expression signatures predict outcome in non-muscle-invasive bladder carcinoma: a multicenter validation study. Clin Cancer Res 13:3545–3551PubMedCrossRef Dyrskjot L, Zieger K, Real FX et al (2007) Gene expression signatures predict outcome in non-muscle-invasive bladder carcinoma: a multicenter validation study. Clin Cancer Res 13:3545–3551PubMedCrossRef
17.
Zurück zum Zitat Eichelberg C, Chun FK, Bedke J et al (2013) Epithelial cell adhesion molecule is an independent prognostic marker in clear cell renal carcinoma. Int J Cancer 132:2948–2955PubMedCrossRef Eichelberg C, Chun FK, Bedke J et al (2013) Epithelial cell adhesion molecule is an independent prognostic marker in clear cell renal carcinoma. Int J Cancer 132:2948–2955PubMedCrossRef
18.
Zurück zum Zitat El Gammal AT, Bruchmann M, Zustin J et al (2010) Chromosome 8p deletions and 8q gains are associated with tumor progression and poor prognosis in prostate cancer. Clin Cancer Res 16:56–64CrossRef El Gammal AT, Bruchmann M, Zustin J et al (2010) Chromosome 8p deletions and 8q gains are associated with tumor progression and poor prognosis in prostate cancer. Clin Cancer Res 16:56–64CrossRef
19.
Zurück zum Zitat Erbersdobler A, Isbarn H, Dix K et al (2009) Prognostic value of microvessel density in prostate cancer: a tissue microarray study. World J Urol 28: 687–692PubMedCrossRef Erbersdobler A, Isbarn H, Dix K et al (2009) Prognostic value of microvessel density in prostate cancer: a tissue microarray study. World J Urol 28: 687–692PubMedCrossRef
20.
Zurück zum Zitat Fleischmann A, Schlomm T, Huland H et al (2008) Distinct subcellular expression patterns of neutral endopeptidase (CD10) in prostate cancer predict diverging clinical courses in surgically treated patients. Clin Cancer Res 14:7838–7842PubMedCrossRef Fleischmann A, Schlomm T, Huland H et al (2008) Distinct subcellular expression patterns of neutral endopeptidase (CD10) in prostate cancer predict diverging clinical courses in surgically treated patients. Clin Cancer Res 14:7838–7842PubMedCrossRef
21.
Zurück zum Zitat Fleischmann A, Schlomm T, Kollermann J et al (2009) Immunological microenvironment in prostate cancer: high mast cell densities are associated with favorable tumor characteristics and good prognosis. Prostate 69:976–981PubMedCrossRef Fleischmann A, Schlomm T, Kollermann J et al (2009) Immunological microenvironment in prostate cancer: high mast cell densities are associated with favorable tumor characteristics and good prognosis. Prostate 69:976–981PubMedCrossRef
22.
Zurück zum Zitat Garcia-Donas J, Esteban E, Leandro-Garcia LJ et al (2011) Single nucleotide polymorphism associations with response and toxic effects in patients with advanced renal-cell carcinoma treated with first-line sunitinib: a multicentre, observational, prospective study. Lancet Oncol 12:1143–1150PubMedCrossRef Garcia-Donas J, Esteban E, Leandro-Garcia LJ et al (2011) Single nucleotide polymorphism associations with response and toxic effects in patients with advanced renal-cell carcinoma treated with first-line sunitinib: a multicentre, observational, prospective study. Lancet Oncol 12:1143–1150PubMedCrossRef
23.
Zurück zum Zitat Graefen M, Ahyai S, Heuer R et al (2008) Active surveillance for prostate cancer. Urologe A 47:261–269PubMedCrossRef Graefen M, Ahyai S, Heuer R et al (2008) Active surveillance for prostate cancer. Urologe A 47:261–269PubMedCrossRef
24.
25.
Zurück zum Zitat Guo G, Sun X, Chen C et al (2013) Whole-genome and whole-exome sequencing of bladder cancer identifies frequent alterations in genes involved in sister chromatid cohesion and segregation. Nat Genet 45:1459–1463PubMedCrossRef Guo G, Sun X, Chen C et al (2013) Whole-genome and whole-exome sequencing of bladder cancer identifies frequent alterations in genes involved in sister chromatid cohesion and segregation. Nat Genet 45:1459–1463PubMedCrossRef
26.
Zurück zum Zitat Hakimi AA, Ostrovnaya I, Reva B et al (2013) Adverse outcomes in clear cell renal cell carcinoma with mutations of 3p21 epigenetic regulators BAP1 and SETD2: a report by MSKCC and the KIRC TCGA research network. Clin Cancer Res 19:3259–3267PubMedCrossRef Hakimi AA, Ostrovnaya I, Reva B et al (2013) Adverse outcomes in clear cell renal cell carcinoma with mutations of 3p21 epigenetic regulators BAP1 and SETD2: a report by MSKCC and the KIRC TCGA research network. Clin Cancer Res 19:3259–3267PubMedCrossRef
27.
Zurück zum Zitat Hauser S, Wulfken LM, Holdenrieder S et al (2012) Analysis of serum microRNAs (miR-26a-2*, miR-191, miR-337-3p and miR-378) as potential biomarkers in renal cell carcinoma. Cancer Epidemiol 36:391–394PubMedCrossRef Hauser S, Wulfken LM, Holdenrieder S et al (2012) Analysis of serum microRNAs (miR-26a-2*, miR-191, miR-337-3p and miR-378) as potential biomarkers in renal cell carcinoma. Cancer Epidemiol 36:391–394PubMedCrossRef
28.
Zurück zum Zitat Heinzelmann J, Henning B, Sanjmyatav J et al (2011) Specific miRNA signatures are associated with metastasis and poor prognosis in clear cell renal cell carcinoma. World J Urol 29:367–373PubMedCrossRef Heinzelmann J, Henning B, Sanjmyatav J et al (2011) Specific miRNA signatures are associated with metastasis and poor prognosis in clear cell renal cell carcinoma. World J Urol 29:367–373PubMedCrossRef
29.
Zurück zum Zitat Hildebrandt MA, Gu J, Lin J et al (2010) Hsa-miR-9 methylation status is associated with cancer development and metastatic recurrence in patients with clear cell renal cell carcinoma. Oncogene 29:5724–5728PubMedCrossRef Hildebrandt MA, Gu J, Lin J et al (2010) Hsa-miR-9 methylation status is associated with cancer development and metastatic recurrence in patients with clear cell renal cell carcinoma. Oncogene 29:5724–5728PubMedCrossRef
30.
Zurück zum Zitat Hoffmann AC, Wild P, Leicht C et al (2010) MDR1 and ERCC1 expression predict outcome of patients with locally advanced bladder cancer receiving adjuvant chemotherapy. Neoplasia 12:628–636PubMedCentralPubMed Hoffmann AC, Wild P, Leicht C et al (2010) MDR1 and ERCC1 expression predict outcome of patients with locally advanced bladder cancer receiving adjuvant chemotherapy. Neoplasia 12:628–636PubMedCentralPubMed
31.
Zurück zum Zitat Kapur P, Pena-Llopis S, Christie A et al (2013) Effects on survival of BAP1 and PBRM1 mutations in sporadic clear-cell renal-cell carcinoma: a retrospective analysis with independent validation. Lancet Oncol 14:159–167PubMedCrossRef Kapur P, Pena-Llopis S, Christie A et al (2013) Effects on survival of BAP1 and PBRM1 mutations in sporadic clear-cell renal-cell carcinoma: a retrospective analysis with independent validation. Lancet Oncol 14:159–167PubMedCrossRef
32.
Zurück zum Zitat Klatte T, Rao PN, Martino M de et al (2009) Cytogenetic profile predicts prognosis of patients with clear cell renal cell carcinoma. J Clin Oncol 27:746–753PubMedCrossRef Klatte T, Rao PN, Martino M de et al (2009) Cytogenetic profile predicts prognosis of patients with clear cell renal cell carcinoma. J Clin Oncol 27:746–753PubMedCrossRef
33.
Zurück zum Zitat Klatte T, Seligson DB, LaRochelle J et al (2009) Molecular signatures of localized clear cell renal cell carcinoma to predict disease-free survival after nephrectomy. Cancer Epidemiol Biomarkers Prev 18:894–900PubMedCrossRef Klatte T, Seligson DB, LaRochelle J et al (2009) Molecular signatures of localized clear cell renal cell carcinoma to predict disease-free survival after nephrectomy. Cancer Epidemiol Biomarkers Prev 18:894–900PubMedCrossRef
35.
Zurück zum Zitat Kluth M, Harasimowicz S, Burkhardt L et al (2014) Clinical significance of different types of p53 gene alteration in surgically treated prostate cancer. Int J Cancer (Epub ahead of print). doi: 10.1002/ijc.28784 Kluth M, Harasimowicz S, Burkhardt L et al (2014) Clinical significance of different types of p53 gene alteration in surgically treated prostate cancer. Int J Cancer (Epub ahead of print). doi: 10.1002/ijc.28784
36.
Zurück zum Zitat Kluth M, Hesse J, Heinl A et al (2013) Genomic deletion of MAP3K7 at 6q12-22 is associated with early PSA recurrence in prostate cancer and absence of TMPRSS2:ERG fusions. Mod Pathol 26:975–983PubMedCrossRef Kluth M, Hesse J, Heinl A et al (2013) Genomic deletion of MAP3K7 at 6q12-22 is associated with early PSA recurrence in prostate cancer and absence of TMPRSS2:ERG fusions. Mod Pathol 26:975–983PubMedCrossRef
37.
Zurück zum Zitat Krohn A, Diedler T, Burkhardt L et al (2012) Genomic deletion of PTEN is associated with tumor progression and early PSA recurrence in ERG fusion-positive and fusion-negative prostate cancer. Am J Pathol 181:401–412PubMedCrossRef Krohn A, Diedler T, Burkhardt L et al (2012) Genomic deletion of PTEN is associated with tumor progression and early PSA recurrence in ERG fusion-positive and fusion-negative prostate cancer. Am J Pathol 181:401–412PubMedCrossRef
38.
Zurück zum Zitat Laurberg JR, Brems-Eskildsen AS, Nordentoft I et al (2012) Expression of TIP60 (tat-interactive protein) and MRE11 (meiotic recombination 11 homolog) predict treatment-specific outcome of localised invasive bladder cancer. BJU Int 110:1228–1236CrossRef Laurberg JR, Brems-Eskildsen AS, Nordentoft I et al (2012) Expression of TIP60 (tat-interactive protein) and MRE11 (meiotic recombination 11 homolog) predict treatment-specific outcome of localised invasive bladder cancer. BJU Int 110:1228–1236CrossRef
39.
Zurück zum Zitat Lindgren D, Frigyesi A, Gudjonsson S et al (2010) Combined gene expression and genomic profiling define two intrinsic molecular subtypes of urothelial carcinoma and gene signatures for molecular grading and outcome. Cancer Res 70:3463–3472PubMedCrossRef Lindgren D, Frigyesi A, Gudjonsson S et al (2010) Combined gene expression and genomic profiling define two intrinsic molecular subtypes of urothelial carcinoma and gene signatures for molecular grading and outcome. Cancer Res 70:3463–3472PubMedCrossRef
40.
Zurück zum Zitat Minner S, De Silva C, Rink M et al (2012) Reduced CD151 expression is related to advanced tumour stage in urothelial bladder cancer. Pathology 44:448–452PubMedCrossRef Minner S, De Silva C, Rink M et al (2012) Reduced CD151 expression is related to advanced tumour stage in urothelial bladder cancer. Pathology 44:448–452PubMedCrossRef
41.
Zurück zum Zitat Minner S, Enodien M, Sirma H et al (2011) ERG status is unrelated to PSA recurrence in radically operated prostate cancer in the absence of antihormonal therapy. Clin Cancer Res 17:5878–5888PubMedCrossRef Minner S, Enodien M, Sirma H et al (2011) ERG status is unrelated to PSA recurrence in radically operated prostate cancer in the absence of antihormonal therapy. Clin Cancer Res 17:5878–5888PubMedCrossRef
42.
Zurück zum Zitat Minner S, Jessen B, Stiedenroth L et al (2010) Low level HER2 overexpression is associated with rapid tumor cell proliferation and poor prognosis in prostate cancer. Clin Cancer Res 16:1553–1560PubMedCrossRef Minner S, Jessen B, Stiedenroth L et al (2010) Low level HER2 overexpression is associated with rapid tumor cell proliferation and poor prognosis in prostate cancer. Clin Cancer Res 16:1553–1560PubMedCrossRef
43.
Zurück zum Zitat Minner S, Wittmer C, Graefen M et al (2011) High level PSMA expression is associated with early PSA recurrence in surgically treated prostate cancer. Prostate 71:281–288PubMedCrossRef Minner S, Wittmer C, Graefen M et al (2011) High level PSMA expression is associated with early PSA recurrence in surgically treated prostate cancer. Prostate 71:281–288PubMedCrossRef
44.
Zurück zum Zitat Monzon FA, Alvarez K, Peterson L et al (2011) Chromosome 14q loss defines a molecular subtype of clear-cell renal cell carcinoma associated with poor prognosis. Mod Pathol 24:1470–1479PubMedCrossRef Monzon FA, Alvarez K, Peterson L et al (2011) Chromosome 14q loss defines a molecular subtype of clear-cell renal cell carcinoma associated with poor prognosis. Mod Pathol 24:1470–1479PubMedCrossRef
45.
Zurück zum Zitat Muller J, Ehlers A, Burkhardt L et al (2012) Loss of p(Ser2448) -mTOR expression is linked to adverse prognosis and tumor progression in ERG-fusion-positive cancers. Int J Cancer 132:1333–1340PubMedCrossRef Muller J, Ehlers A, Burkhardt L et al (2012) Loss of p(Ser2448) -mTOR expression is linked to adverse prognosis and tumor progression in ERG-fusion-positive cancers. Int J Cancer 132:1333–1340PubMedCrossRef
46.
Zurück zum Zitat Nishikawa M, Miyake H, Harada K et al (2014) Expression level of phosphorylated-4E-binding protein 1 in radical nephrectomy specimens as a prognostic predictor in patients with metastatic renal cell carcinoma treated with mammalian target of rapamycin inhibitors. Med Oncol 31:792PubMedCrossRef Nishikawa M, Miyake H, Harada K et al (2014) Expression level of phosphorylated-4E-binding protein 1 in radical nephrectomy specimens as a prognostic predictor in patients with metastatic renal cell carcinoma treated with mammalian target of rapamycin inhibitors. Med Oncol 31:792PubMedCrossRef
47.
Zurück zum Zitat Nordentoft I, Dyrskjot L, Bodker JS et al (2011) Increased expression of transcription factor TFAP2alpha correlates with chemosensitivity in advanced bladder cancer. BMC Cancer 11:135PubMedCentralPubMedCrossRef Nordentoft I, Dyrskjot L, Bodker JS et al (2011) Increased expression of transcription factor TFAP2alpha correlates with chemosensitivity in advanced bladder cancer. BMC Cancer 11:135PubMedCentralPubMedCrossRef
48.
Zurück zum Zitat Parker AS, Leibovich BC, Lohse CM et al (2009) Development and evaluation of BioScore: a biomarker panel to enhance prognostic algorithms for clear cell renal cell carcinoma. Cancer 115:2092–2103PubMedCentralPubMedCrossRef Parker AS, Leibovich BC, Lohse CM et al (2009) Development and evaluation of BioScore: a biomarker panel to enhance prognostic algorithms for clear cell renal cell carcinoma. Cancer 115:2092–2103PubMedCentralPubMedCrossRef
49.
Zurück zum Zitat Prior C, Perez-Gracia JL, Garcia-Donas J et al (2014) Identification of tissue microRNAs predictive of sunitinib activity in patients with metastatic renal cell carcinoma. PloS One 9:86263CrossRef Prior C, Perez-Gracia JL, Garcia-Donas J et al (2014) Identification of tissue microRNAs predictive of sunitinib activity in patients with metastatic renal cell carcinoma. PloS One 9:86263CrossRef
50.
Zurück zum Zitat Redova M, Poprach A, Nekvindova J et al (2012) Circulating miR-378 and miR-451 in serum are potential biomarkers for renal cell carcinoma. J Transl Med 10:55PubMedCentralPubMedCrossRef Redova M, Poprach A, Nekvindova J et al (2012) Circulating miR-378 and miR-451 in serum are potential biomarkers for renal cell carcinoma. J Transl Med 10:55PubMedCentralPubMedCrossRef
51.
Zurück zum Zitat Sakr WA, Grignon DJ, Crissman JD et al (1994) High grade prostatic intraepithelial neoplasia (HGPIN) and prostatic adenocarcinoma between the ages of 20–69: an autopsy study of 249 cases. In Vivo 8:439–443PubMed Sakr WA, Grignon DJ, Crissman JD et al (1994) High grade prostatic intraepithelial neoplasia (HGPIN) and prostatic adenocarcinoma between the ages of 20–69: an autopsy study of 249 cases. In Vivo 8:439–443PubMed
52.
Zurück zum Zitat Sanjmyatav J, Junker K, Matthes S et al (2011) Identification of genomic alterations associated with metastasis and cancer specific survival in clear cell renal cell carcinoma. J Urol 186:2078–2083PubMedCrossRef Sanjmyatav J, Junker K, Matthes S et al (2011) Identification of genomic alterations associated with metastasis and cancer specific survival in clear cell renal cell carcinoma. J Urol 186:2078–2083PubMedCrossRef
53.
Zurück zum Zitat Sato Y, Yoshizato T, Shiraishi Y et al (2013) Integrated molecular analysis of clear-cell renal cell carcinoma. Nat Genet 45:860–867PubMedCrossRef Sato Y, Yoshizato T, Shiraishi Y et al (2013) Integrated molecular analysis of clear-cell renal cell carcinoma. Nat Genet 45:860–867PubMedCrossRef
54.
Zurück zum Zitat Schlomm T, Erbersdobler A, Mirlacher M et al (2007) Molecular staging of prostate cancer in the year 2007. World J Urol 25:19–30PubMedCrossRef Schlomm T, Erbersdobler A, Mirlacher M et al (2007) Molecular staging of prostate cancer in the year 2007. World J Urol 25:19–30PubMedCrossRef
55.
Zurück zum Zitat Schlomm T, Iwers L, Kirstein P et al (2008) Clinical significance of p53 alterations in surgically treated prostate cancers. Mod Pathol 21:1371–1379PubMedCrossRef Schlomm T, Iwers L, Kirstein P et al (2008) Clinical significance of p53 alterations in surgically treated prostate cancers. Mod Pathol 21:1371–1379PubMedCrossRef
56.
Zurück zum Zitat Schlomm T, Kirstein P, Iwers L et al (2007) Clinical significance of epidermal growth factor receptor protein overexpression and gene copy number gains in prostate cancer. Clin Cancer Res 13:6579–6584PubMedCrossRef Schlomm T, Kirstein P, Iwers L et al (2007) Clinical significance of epidermal growth factor receptor protein overexpression and gene copy number gains in prostate cancer. Clin Cancer Res 13:6579–6584PubMedCrossRef
57.
Zurück zum Zitat Sjodahl G, Lovgren K, Lauss M et al (2013) Toward a molecular pathologic classification of urothelial carcinoma. Am J Pathol 183:681–691PubMedCrossRef Sjodahl G, Lovgren K, Lauss M et al (2013) Toward a molecular pathologic classification of urothelial carcinoma. Am J Pathol 183:681–691PubMedCrossRef
58.
Zurück zum Zitat Slaby O, Redova M, Poprach A et al (2012) Identification of MicroRNAs associated with early relapse after nephrectomy in renal cell carcinoma patients. Genes Chromosomes Cancer 51:707–716PubMedCrossRef Slaby O, Redova M, Poprach A et al (2012) Identification of MicroRNAs associated with early relapse after nephrectomy in renal cell carcinoma patients. Genes Chromosomes Cancer 51:707–716PubMedCrossRef
59.
Zurück zum Zitat Smith SC, Baras AS, Dancik G et al (2011) A 20-gene model for molecular nodal staging of bladder cancer: development and prospective assessment. Lancet Oncol 12:137–143PubMedCentralPubMedCrossRef Smith SC, Baras AS, Dancik G et al (2011) A 20-gene model for molecular nodal staging of bladder cancer: development and prospective assessment. Lancet Oncol 12:137–143PubMedCentralPubMedCrossRef
60.
Zurück zum Zitat Teixeira AL, Ferreira M, Silva J et al (2013) Higher circulating expression levels of miR-221 associated with poor overall survival in renal cell carcinoma patients. Tumour Biol 8(8):72419 Teixeira AL, Ferreira M, Silva J et al (2013) Higher circulating expression levels of miR-221 associated with poor overall survival in renal cell carcinoma patients. Tumour Biol 8(8):72419
61.
Zurück zum Zitat The Cancer Genome Atlas Research N (2014) Comprehensive molecular characterization of urothelial bladder carcinoma. Nature 505:495–501CrossRef The Cancer Genome Atlas Research N (2014) Comprehensive molecular characterization of urothelial bladder carcinoma. Nature 505:495–501CrossRef
62.
Zurück zum Zitat Veldt AA van der, Eechoute K, Gelderblom H et al (2011) Genetic polymorphisms associated with a prolonged progression-free survival in patients with metastatic renal cell cancer treated with sunitinib. Clin Cancer Res 17:620–629PubMedCrossRef Veldt AA van der, Eechoute K, Gelderblom H et al (2011) Genetic polymorphisms associated with a prolonged progression-free survival in patients with metastatic renal cell cancer treated with sunitinib. Clin Cancer Res 17:620–629PubMedCrossRef
63.
Zurück zum Zitat Kessel KE van, Kompier LC, Bekker-Grob EW de et al (2013) FGFR3 mutation analysis in voided urine samples to decrease cystoscopies and cost in nonmuscle invasive bladder cancer surveillance: a comparison of 3 strategies. J Urol 189:1676–1681PubMedCrossRef Kessel KE van, Kompier LC, Bekker-Grob EW de et al (2013) FGFR3 mutation analysis in voided urine samples to decrease cystoscopies and cost in nonmuscle invasive bladder cancer surveillance: a comparison of 3 strategies. J Urol 189:1676–1681PubMedCrossRef
64.
Zurück zum Zitat Rhijn BW van, Kwast TH van der, Liu L et al (2012) The FGFR3 mutation is related to favorable pT1 bladder cancer. J Urol 187:310–314PubMed Rhijn BW van, Kwast TH van der, Liu L et al (2012) The FGFR3 mutation is related to favorable pT1 bladder cancer. J Urol 187:310–314PubMed
65.
Zurück zum Zitat Rhijn BW van, Vis AN, Kwast TH van der et al (2003) Molecular grading of urothelial cell carcinoma with fibroblast growth factor receptor 3 and MIB-1 is superior to pathologic grade for the prediction of clinical outcome. J Clin Oncol 21:1912–1921PubMedCrossRef Rhijn BW van, Vis AN, Kwast TH van der et al (2003) Molecular grading of urothelial cell carcinoma with fibroblast growth factor receptor 3 and MIB-1 is superior to pathologic grade for the prediction of clinical outcome. J Clin Oncol 21:1912–1921PubMedCrossRef
66.
Zurück zum Zitat Weischenfeldt J, Simon R, Feuerbach L et al (2013) Integrative genomic analyses reveal androgen-driven somatic alteration landscape in early-onset prostate cancer. Cancer Cell 23:159–170PubMedCrossRef Weischenfeldt J, Simon R, Feuerbach L et al (2013) Integrative genomic analyses reveal androgen-driven somatic alteration landscape in early-onset prostate cancer. Cancer Cell 23:159–170PubMedCrossRef
68.
Zurück zum Zitat Wu X, Weng L, Li X et al (2012) Identification of a 4-microRNA signature for clear cell renal cell carcinoma metastasis and prognosis. PloS One 7:35661CrossRef Wu X, Weng L, Li X et al (2012) Identification of a 4-microRNA signature for clear cell renal cell carcinoma metastasis and prognosis. PloS One 7:35661CrossRef
69.
Zurück zum Zitat Xu CF, Bing NX, Ball HA et al (2011) Pazopanib efficacy in renal cell carcinoma: evidence for predictive genetic markers in angiogenesis-related and exposure-related genes. J Clin Oncol 29:2557–2564PubMedCrossRef Xu CF, Bing NX, Ball HA et al (2011) Pazopanib efficacy in renal cell carcinoma: evidence for predictive genetic markers in angiogenesis-related and exposure-related genes. J Clin Oncol 29:2557–2564PubMedCrossRef
70.
Zurück zum Zitat Xu C, Johnson T, Choueiri T et al (2013) Association of IL8 polymorphisms with overall survival in patients with renal cell carcinoma in COMPARZ (pazopanib versus sunitinib phase III study). J Clin Oncol 31(Suppl):4519 Xu C, Johnson T, Choueiri T et al (2013) Association of IL8 polymorphisms with overall survival in patients with renal cell carcinoma in COMPARZ (pazopanib versus sunitinib phase III study). J Clin Oncol 31(Suppl):4519
Metadaten
Titel
Prognostische und prädiktive molekulare Marker urologischer Tumoren
verfasst von
A. Hartmann
T. Schlomm
S. Bertz
J. Heinzelmann
S. Hölters
R. Simon
R. Stoehr
Prof. Dr. K. Junker
Publikationsdatum
01.04.2014
Verlag
Springer Berlin Heidelberg
Erschienen in
Die Urologie / Ausgabe 4/2014
Print ISSN: 2731-7064
Elektronische ISSN: 2731-7072
DOI
https://doi.org/10.1007/s00120-014-3442-3

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