Martin Filipits

University of Vienna, Wien, Vienna, Austria

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Publications (158)975.15 Total impact

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    ABSTRACT: Background: Plasma fibrinogen may be involved in several stages of cancer progression. Clinical studies have demonstrated that pretreatment plasma fibrinogen is associated with poor survival in various cancers. The aim of this meta-analysis was to examine the prognostic effect of circulating fibrinogen in solid tumors. Materials and methods: We searched Medline, EMBASE, Cochrane Database of Systematic Reviews, and meeting proceedings to identify studies assessing the effect of pretreatment plasma fibrinogen on survival of cancer patients. Pooled multivariable-adjusted hazard ratios (HRs) for overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS) were estimated using random-effects models. Results: Data from 52 observational studies and 15,371 patients were summarized. An elevated baseline plasma fibrinogen was significantly associated with worse OS (pooled HR=1.69; 95% CI=1.48-1.92). The highest negative effect of elevated plasma fibrinogen on OS was demonstrated in renal cell carcinoma (pooled HR=2.22), followed by head and neck cancer (pooled HR=2.02), and colorectal cancer (pooled HR=1.89). The adverse prognostic impact of high plasma fibrinogen remained in both non-metastatic and metastatic disease and patients of different ethnicity. Patients with high baseline fibrinogen had a significantly shorter DFS (pooled HR=1.52) and CSS (pooled HR=2.50). Conclusions: An elevated pretreatment plasma fibrinogen significantly correlates with decreased survival in patients with solid tumors. Future clinical trials are warranted to determine whether plasma fibrinogen could be incorporated in cancer staging systems and whether fibrinogen-lowering therapies have a favorable effect on disease recurrence and mortality.
    Cancer Treatment Reviews 10/2015; DOI:10.1016/j.ctrv.2015.10.002 · 7.59 Impact Factor
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    ABSTRACT: Background/aim: In light of the controversial published literature, this study aims to examine the potential prognostic role of AR immunohistochemical expression in triple negative breast cancer (TNBC). Patients and methods: Ninety patients with TNBC were included in this study; the associations between AR expression (Allred score), clinicopathological variables (stage, grade, histological subtype, tumor size, nodal status, age at diagnosis, Ki67 expression, and p53 expression), and overall survival were evaluated. Results: AR expression was not associated with stage, grade, histological subtype, tumor size, nodal status, age at diagnosis, Ki67 expression, and p53 expression. AR immunopositivity was not associated with overall survival either at the univariate or at the multivariate Cox regression analysis (multivariate hazard ratio =0.66, 95% confidence interval: 0.26-1.70, P=0.393). Conclusion: AR expression does not seem to play a prognostic role in TNBC.
    OncoTargets and Therapy 08/2015; 8:1843-7. DOI:10.2147/OTT.S78254 · 2.31 Impact Factor

  • Cancer Research 05/2015; 75(9 Supplement):P5-18-01-P5-18-01. DOI:10.1158/1538-7445.SABCS14-P5-18-01 · 9.33 Impact Factor

  • Cancer Research 05/2015; 75(9 Supplement):S2-06-S2-06. DOI:10.1158/1538-7445.SABCS14-S2-06 · 9.33 Impact Factor

  • Cancer Research 05/2015; 75(9 Supplement):P5-02-10-P5-02-10. DOI:10.1158/1538-7445.SABCS14-P5-02-10 · 9.33 Impact Factor
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    ABSTRACT: In the adjuvant treatment of hormone receptor positive (HR+) breast cancer, variables like tumour size, grade and nodal status have great impact on therapy decisions. As most node-positive patients with HR+ breast cancer currently receive adjuvant chemotherapy improved methods for characterisation of individuals' metastasis risk are needed to reduce overtreatment. Tissue specimens from node-positive patients of the ABCSG-8 and ATAC trials who received adjuvant tamoxifen and/or anastrozole were included in this study. Analysing RNA from paraffin blocks using the PAM50 test, the primary objective was to evaluate the prognostic information of the risk of recurrence (ROR) score added to combined clinical standard variables in patients with one positive node (1N+) and in patients with two or three positive nodes (2-3N+), using log-likelihood ratio tests. At a median follow-up of 9.6 years, distant metastases occurred in 97 (18%) out of 543 node positive patients. In a multivariate analysis, the PAM50-derived ROR score provided reliable prognostic information in addition to and beyond established clinical factors for 1N+ (P<0.0001) and 2-3N+ patients (P=0.0002). Ten year distant recurrence risk was significantly increased in the high risk compared to the low risk group derived from ROR score for 1N+ (25.5%, 95% CI 17.5%-36.1% vs. 6.6%, 95% CI 3.3%-12.8%) and compared to the combined low/intermediate risk group for 2-3N+ patients (33.7%, 95% CI 25.5%-43.8% vs. 12.5%, 95% CI 6.6%-22.8%). Additionally, the luminal A intrinsic subtype exhibited significantly lower risk of distant recurrence compared to the luminal B subtype in 1N+ and 2-3N+ patients. PAM50 ROR score and Intrinsic Subtype can identify node-positive patient subgroups with limited risk of metastasis after endocrine therapy, for whom adjuvant chemotherapy can be spared. The PAM50 test is a valuable tool in determining treatment for node-positive EBC patients. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email:
    Annals of Oncology 05/2015; 26(8). DOI:10.1093/annonc/mdv215 · 7.04 Impact Factor
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    ABSTRACT: Ovarian cancer (OC) is caused by genetic aberrations in networks that control growth and survival. Importantly, aberrant cancer metabolism interacts with oncogenic signaling providing additional drug targets. Tumors overexpress the lipogenic enzyme fatty acid synthase (FASN) and are inhibited by FASN-blockers, whereas normal cells are FASN-negative and FASN-inhibitor-resistant. Here we demonstrate that this holds true when ovarian/oviductal cells reside in their autochthonous tissues, whereas in culture they express FASN and are FASN-inhibitor-sensitive. Upon subculture, non-malignant cells cease growth, express senescence-associated-β-galactosidase, lose FASN and become FASN-inhibitor-resistant. Immortalized ovarian/oviductal epithelial cell lines - although resisting senescence - reveal distinct growth activities, which correlate with FASN-levels and FASN-drug-sensitivities. Accordingly, ectopic FASN stimulates growth in these cells. Moreover, FASN-levels and lipogenic activities affect cellular lipid composition as demonstrated by thin-layer chromatography. Correlation between proliferation and FASN-levels was finally evaluated in cancer cells such as HOC-7, which contain subclones with variable differentiation/senescence and corresponding FASN-expression/FASN-drug-sensitivity. Interestingly, senescent phenotypes can be induced in parental HOC-7 by differentiating agents. In OC cells, FASN-drugs induce cell cycle-blockade in S and/or G2/M and stimulate apoptosis, whereas in normal cells they only cause cell cycle-deceleration without apoptosis. Thus normal cells, although growth-inhibited, may survive and recover from FASN-blockade, whereas malignant cells get extinguished. FASN-expression and FASN-drug-sensitivity are directly linked to cell growth and correlate with transformation/differentiation/senescence only indirectly. FASN is therefore a metabolic marker of cell proliferation rather than a marker of malignancy and is a useful target for future drug development. © 2014 Wiley Periodicals, Inc.
    International Journal of Cancer 05/2015; 136(9). DOI:10.1002/ijc.29261 · 5.09 Impact Factor
  • F Fitzal · M Filipits · M Rudas · R Greil · O Dietze · H Samonigg · S Lax · W Herz · P Dubsky · R Bartsch · R Kronenwett · M Gnant ·
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    ABSTRACT: The aim of this study was to examine whether EndoPredict (EP), a novel genomic expression test, is effective in predicting local recurrence (LR)-free survival (LRFS) following surgery for breast cancer in postmenopausal women. In addition, we examined whether EP may help tailor local therapy in these patients. From January 1996 to June 2004, 3714 postmenopausal patients were randomly assigned to either tamoxifen or tamoxifen followed by anastrozole within the prospective ABCSG 8 trial. Using assay scores from EP, we classified breast tumour blocks as either low or high risk for recurrence. Data were gathered from 1324 patients. The median follow-up was 72.3 months and the cumulative incidence of LR was 2.6% (0.4% per year). The risk of LR over a 10-year period among patients with high-risk lesions (n=683) was significantly higher (LRFS=91%) when compared with patients with low-risk lesions (n=641) (10-year LRFS=97.5%) (HR: 1.31 (1.16-1.48) P<0.005). The groups that received breast conservation surgery (BCT) and mastectomy (MX) had similar LR rates (P=0.879). Radiotherapy (RT) after BCT significantly improved LRFS in the cohorts predicted by EP to be low-risk for LR (received RT: n=436, 10-year LRFS 99.8%; did not receive RT: n=63, 10-year LRFS 83.6%, P<0.005). EndoPredict is an effective prognostic tool for predicting LRFS. Among postmenopausal, low-risk patients, EP does not appear to be useful for tailoring local therapy.British Journal of Cancer advance online publication 24 March 2015; doi:10.1038/bjc.2015.98
    British Journal of Cancer 03/2015; 112(8). DOI:10.1038/bjc.2015.98 · 4.84 Impact Factor
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    ABSTRACT: The transcription factor Ecotropic Virus Integration site 1 (EVI1) regulates cellular proliferation, differentiation, and apoptosis, and its overexpression contributes to an aggressive course of disease in myeloid leukemias and other malignancies. Notwithstanding, knowledge about the target genes mediating its biological and pathological functions remains limited. We therefore aimed to identify and characterize novel EVI1 target genes in human myeloid cells. U937T_EVI1, a human myeloid cell line expressing EVI1 in a tetracycline regulable manner, was subjected to gene expression profiling. qRT-PCR was used to confirm the regulation of membrane-spanning-4-domains subfamily-A member-3 (MS4A3) by EVI1. Reporter constructs containing various parts of the MS4A3 upstream region were employed in luciferase assays, and binding of EVI1 to the MS4A3 promoter was investigated by chromatin immunoprecipitation. U937 derivative cell lines experimentally expressing EVI1 and/or MS4A3 were generated by retroviral transduction, and tested for their tumorigenicity by subcutaneous injection into severe combined immunodeficient mice. Gene expression microarray analysis identified 27 unique genes that were up-regulated, and 29 unique genes that were down-regulated, in response to EVI1 induction in the human myeloid cell line U937T. The most strongly repressed gene was MS4A3, and its down-regulation by EVI1 was confirmed by qRT-PCR in additional, independent experimental model systems. MS4A3 mRNA levels were also negatively correlated with those of EVI1 in several published AML data sets. Reporter gene assays and chromatin immunoprecipitation showed that EVI1 regulated MS4A3 via direct binding to a promoter proximal region. Experimental re-expression of MS4A3 in an EVI1 overexpressing cell line counteracted the tumor promoting effect of EVI1 in a murine xenograft model by increasing the rate of apoptosis. Our data reveal MS4A3 as a novel direct target of EVI1 in human myeloid cells, and show that its repression plays a role in EVI1 mediated tumor aggressiveness.
    Journal of Hematology & Oncology 03/2015; 8(28). DOI:10.1186/s13045-015-0124-6 · 4.81 Impact Factor
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    ABSTRACT: Epithelial-to-mesenchymal transition (EMT) is a central developmental process implicated in cancer metastasis. Here we show that the tyrosine kinase PYK2 enhances cell migration and invasion and potentiates EMT in human breast carcinoma. EMT inducer, such as EGF, induces rapid phosphorylation of PYK2 and its translocation to early endosomes where it co-localizes with EGFR and sustains its downstream signals. Furthermore, PYK2 enhances EGF-induced STAT3-phosphorylation, while phospho-STAT3 directly binds to PYK2 promoter and regulates PYK2 transcription. STAT3 and PYK2 also enhance c-Met expression, while c-Met augments their phosphorylation, suggesting a positive feedback loop between PYK2-STAT3-c-Met. We propose that PYK2 sustains endosomal-derived receptor signalling and participates in a positive feedback that links cell surface receptor(s) to transcription factor(s) activation, thereby prolonging signalling duration and potentiating EMT. Given the role of EMT in breast cancer metastasis, we also found a significant correlation between PYK2 expression, tumour grade and lymph node metastasis, thus, demonstrating the clinicopathological implication of our findings.
    Nature Communications 02/2015; 6:6064. DOI:10.1038/ncomms7064 · 11.47 Impact Factor
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    ABSTRACT: Background: Estimating the prognosis in malignant pleural mesothelioma (MPM) remains challenging. Thus, the prognostic relevance of Ki67 was studied in MPM. Methods: Ki67 index was determined in a test cohort of 187 cases from three centres. The percentage of Ki67-positive tumour cells was correlated with clinical variables and overall survival (OS). The prognostic power of Ki67 index was compared with other prognostic factors and re-evaluated in an independent cohort (n=98). Results: Patients with Ki67 higher than median (>15%) had significantly (P<0.001) shorter median OS (7.5 months) than those with low Ki67 (19.1 months). After multivariate survival analyses, Ki67 proved to be-beside histology and treatment-an independent prognostic marker in MPM (hazard ratio (HR): 2.1, P<0.001). Interestingly, Ki67 was prognostic exclusively in epithelioid (P<0.001) but not in non-epithelioid subtype. Furthermore, Ki67 index was significantly lower in post-chemotherapy samples when compared with chemo-naive cases. The prognostic power was comparable to other recently published prognostic factors (CRP, fibrinogen, neutrophil-to-leukocyte ratio (NLR) and nuclear grading score) and was recapitulated in the validation cohort (P=0.048). Conclusion: This multicentre study demonstrates that Ki67 is an independent and reproducible prognostic factor in epithelioid but not in non-epithelioid MPM and suggests that induction chemotherapy decreases the proliferative capacity of MPM.
    British Journal of Cancer 01/2015; 112(5). DOI:10.1038/bjc.2015.9 · 4.84 Impact Factor
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    ABSTRACT: Myeloid cells lacking STAT3 promote antitumor responses of NK and T cells but it is unknown if this crosstalk affects development of autochthonous tumors. We deleted STAT3 in murine myeloid cells (STAT3(Δm)) and examined the effect on the development of autochthonous colorectal cancers (CRCs). Formation of Azoxymethane/Dextransulfate (AOM/DSS)-induced CRCs was strongly suppressed in STAT3(Δm) mice. Gene expression profiling showed strong activation of T cells in the stroma of STAT3(Δm) CRCs. Moreover, STAT3(Δm) host mice were better able to control the growth of transplanted MC38 colorectal tumor cells which are known to be killed in a T cell-dependent manner. These data suggest that myeloid cells lacking STAT3 control formation of CRCs mainly via cross activation of T cells. Interestingly, the few CRCs that formed in STAT3(Δm) mice displayed enhanced stromalization but appeared normal in size indicating that they have acquired ways to escape enhanced tumor surveillance. We found that CRCs in STAT3(Δm) mice consistently activate STAT3 signaling which is implicated in immune evasion and might be a target to prevent tumor relapse.
    OncoImmunology 01/2015; 4(4):e998529. DOI:10.1080/2162402X.2014.998529 · 6.27 Impact Factor
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    ABSTRACT: We aimed to determine the prognostic significance of receptor activator of nuclear factor kappa-B ligand (RANKL), RANK and osteoprotegerin (OPG) in patients with oral squamous cell carcinoma (OSCC). The protein expression of RANKL, RANK and OPG was assessed by immunohistochemistry on pretreatment biopsies of 93 patients with locally advanced OSCC who received preoperative chemoradiotherapy (CRT). The primary endpoint was cancer-specific survival. Secondary endpoints were correlation of biomarkers with bone invasion and pathological tumor response. Kaplan-Meier curves and Cox regression models were used for survival analyses. A significantly higher OPG expression was demonstrated in patients with malignant bone invasion and non-responders to CRT as compared to patients without bone invasion and responders (p=0.032 and p=0.033, respectively). Multivariate analysis revealed that higher OPG expression was independently associated with shorter cancer-specific survival (p=0.04). The expression status of RANKL and RANK was not significantly related to clinicopathological characteristics and had no impact on survival of OSCC patients. Upregulation of OPG expression is associated with bone invasion, poor pathological tumor regression to neoadjuvant CRT, and worse long-term cancer-specific survival in patients with locally advanced OSCC. Our results indicate that OPG may be a novel prognostic biomarker in oral cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Oral Oncology 12/2014; 51(3). DOI:10.1016/j.oraloncology.2014.11.010 · 3.61 Impact Factor
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    ABSTRACT: The individual risk of recurrence in hormone receptor-positive primary breast cancer patients determines whether adjuvant endocrine therapy should be combined with chemotherapy. Clinicopathological parameters and molecular tests such as EndoPredict(®) (EPclin) can support decision making in patients with estrogen receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative cancer. Using a life-long Markov state transition model, we determined the health economic impact and incremental cost effectiveness of EPclin-based risk stratification in combination with clinical guidelines [German-S3, National Comprehensive Cancer Center Network (NCCN), and St. Gallen] to decide on chemotherapy use. Information on overall and metastasis-free survival came from Austrian Breast & Colorectal Cancer Study Group clinical trials 6/8 (n = 1,619) and published literature. Effectiveness was assessed as quality-adjusted life-years (QALYs). Costs (2010) were assessed from a German third-party payer perspective. Lifetime costs per patient ranged from 28,268 (St.Gallen and EPclin) to 33,756 (NCCN). Due to an imperfect prognostic value and differences in chemotherapy use, strategies achieved between 13.165 QALYs (NCCN) and 13.173 QALYs (EPclin alone) per patient. Using German-S3 as reference, three strategies showed dominant results (St. Gallen and EPclin, German-S3 and EPclin, EPclin alone). Compared to German-S3, the addition of EPclin saved 3,388 and gained 0.002 QALYs per patient. Combining guidelines with EPclin remained preferable in sensitivity analysis. Our study suggests that molecular markers can be sensibly combined with clinical guidelines to determine the risk profile of adjuvant breast cancer patients. Compared with the current German best practice (German-S3), combinations of EPclin with the St. Gallen, German-S3 or NCCN guideline and EPclin alone were dominant from the perspective of the German healthcare system.
    PharmacoEconomics 11/2014; 33(2). DOI:10.1007/s40273-014-0227-x · 2.45 Impact Factor
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    ABSTRACT: Background: Immune checkpoint inhibitors targeting programmed cell death 1 (PD1) or its ligand (PD-L1) showed activity in several cancer types. Methods: We performed immunohistochemistry for CD3, CD8, CD20, HLA-DR, phosphatase and tensin homolog (PTEN), PD-1, and PD-L1 and pyrosequencing for assessment of the O6-methylguanine-methyltransferase (MGMT) promoter methylation status in 135 glioblastoma specimens (117 initial resection, 18 first local recurrence). PD-L1 gene expression was analyzed in 446 cases from The Cancer Genome Atlas. Results: Diffuse/fibrillary PD-L1 expression of variable extent, with or without interspersed epithelioid tumor cells with membranous PD-L1 expression, was observed in 103 of 117 (88.0%) newly diagnosed and 13 of 18 (72.2%) recurrent glioblastoma specimens. Sparse-to-moderate density of tumor-infiltrating lymphocytes (TILs) was found in 85 of 117 (72.6%) specimens (CD3+ 78/117, 66.7%; CD8+ 52/117, 44.4%; CD20+ 27/117, 23.1%; PD1+ 34/117, 29.1%). PD1+ TIL density correlated positively with CD3+ (P < .001), CD8+ (P < .001), CD20+ TIL density (P < .001), and PTEN expression (P = .035). Enrichment of specimens with low PD-L1 gene expression levels was observed in the proneural and G-CIMP glioblastoma subtypes and in specimens with high PD-L1 gene expression in the mesenchymal subtype (P = 5.966e-10). No significant differences in PD-L1 expression or TIL density between initial and recurrent glioblastoma specimens or correlation of PD-L1 expression or TIL density with patient age or outcome were evident. Conclusion: TILs and PD-L1 expression are detectable in the majority of glioblastoma samples but are not related to outcome. Because the target is present, a clinical study with specific immune checkpoint inhibitors seems to be warranted in glioblastoma.
    Neuro-Oncology 10/2014; 17(8). DOI:10.1093/neuonc/nou307 · 5.56 Impact Factor
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    ABSTRACT: Purpose: We have previously shown that the PAM50-based risk of recurrence (ROR) score is significantly correlated with distant recurrence in both the translational research cohort within the Arimidex, Tamoxifen Alone or in Combination (ATAC) trial (TransATAC) and Austrian Breast and Colorectal Cancer Study Group 8 (ABCSG 8) randomized trials. Here, we focus on the ROR score for predicting distant recurrence after 5 years of follow-up in a combined analysis of these two randomized trials. Methods: Long-term follow-up data and tissue samples were obtained from 2,137 postmenopausal women with hormone receptor-positive early-stage breast cancer from the ABCSG 8 and TransATAC trials. We used Cox proportional hazard regression models to determine the prognostic value of ROR for distant recurrence beyond 5 years in the combined data set. Results: A total of 2,137 women who did not have a recurrence 5 years after diagnosis were included in the combined analyses. The Clinical Treatment Score (CTS) was the strongest prognostic factor 5 years after diagnosis (univariable: likelihood ratio [LR] χ(2) = 94.12, bivariable: LR χ(2) = 61.43). The ROR score was significantly prognostic by itself in years 5 to 10. In the node-negative/human epidermal growth factor receptor 2-negative subgroup, more prognostic value for late distant recurrence was added by the ROR score compared with the CTS. Conclusion: The ROR score added clinically meaningful prognostic information to the CTS in all patients and all subgroups in the late follow-up period. These results suggest that the ROR score may be helpful for separating patients into risk groups who could be spared or potentially benefit from extended hormonal therapy beyond 5 years of treatment.
    Journal of Clinical Oncology 10/2014; 33(8). DOI:10.1200/JCO.2014.55.6894 · 18.43 Impact Factor
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    ABSTRACT: Rationale: Malignant pleural mesothelioma is an aggressive malignancy characterized by frequent resistance to chemo- and radiotherapy, poor outcome and limited therapeutic options. Fibroblast growth factors and their receptors are potential targets for cancer therapy but their significance in mesothelioma has remained largely undefined. Objectives: To investigate the anti-mesothelioma potential of fibroblast growth factor receptor 1 inhibition. Methods: Expression of fibroblast growth factors and their receptors was analyzed in mesothelioma cell lines and tissue specimens. Several cell models were used to investigate fibroblast growth factor receptor 1 inhibition in vitro and in combination with cisplatin and irradiation. Mouse intraperitoneal xenotransplant models were used for in vivo validation. Measurements and Main Results: FGFR1, FGF2 and FGF18 were overexpressed in mesothelioma. Stimulation with FGF2 led to increased cell proliferation, migration and transition to a more sarcomatoid phenotype in subsets of mesothelioma cell lines. In contrast, inhibition of FGFR1 by a specific kinase inhibitor or a dominant negative FGFR1 construct led to significantly decreased proliferation, clonogenicity, migration, spheroid formation and G1 cell cycle arrest in several mesothelioma cell lines, accompanied by apoptosis induction, and decreased mitogen-activated protein kinase pathway activity. Reduced tumor growth, proliferation and mitogenic signaling as well as apoptosis induction were also observed in vivo. Importantly, inhibition of FGFR1 synergistically enhanced the cytotoxic effects of ionizing radiation and cisplatin. Conclusions: Our data suggest that the malignant phenotype of mesothelioma cells depends on intact fibroblast growth factor signals, which consequently should be considered as therapeutic targets with a promising chemo- and radio-sensitizing potential.
    American Journal of Respiratory and Critical Care Medicine 09/2014; 190(7). DOI:10.1164/rccm.201404-0658OC · 13.00 Impact Factor
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    ABSTRACT: Background: The external quality assurance (EQA) process aims at establishing laboratory performance levels. Leading European groups in the fields of EQA, Pathology, and Medical and Thoracic Oncology collaborated in a pilot EQA scheme for somatic epidermal growth factor receptor (EGFR) gene mutational analysis in non-small-cell lung cancer (NSCLC). Methods: EQA samples generated from cell lines mimicking clinical samples were provided to participating laboratories, each with a mock clinical case. Participating laboratories performed the analysis using their usual method(s). Anonymous results were assessed and made available to all participants. Two subsequent EQA rounds followed the pilot scheme. Results: One hundred and seventeen labs from 30 countries registered and 91 returned results. Sanger sequencing and a commercial kit were the main methodologies used. The standard of genotyping was suboptimal, with a significant number of genotyping errors made. Only 72 out of 91 (72%) participants passed the EQA. False-negative and -positive results were the main sources of error. The quality of reports submitted was acceptable; most were clear, concise and easy to read. However, some participants reported the genotyping result in the absence of any interpretation and many obscured the interpretation required for clinical care. Conclusions: Even in clinical laboratories, the technical performance of genotyping in EGFR mutation testing for NSCLC can be improved, evident from a high level of diagnostic errors. Robust EQA can contribute to global optimisation of EGFR testing for NSCLC patients.
    British Journal of Cancer 07/2014; 111(2). DOI:10.1038/bjc.2014.353 · 4.84 Impact Factor
  • Michael Knauer · Martin Filipits · Peter Dubsky ·
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    ABSTRACT: During the last decade, besides the well-established clinical-pathological predictors for the risk of late recurrence in breast cancer, such as estrogen receptor status, and T and N stage, a variety of multigene assays have been shown to improve prognostication and prediction in this setting. Several clinical trials have evaluated the role of extended endocrine therapy with tamoxifen (ATLAS) or aromatase inhibitors (MA.17, NSABP-B33 and ABCSG 6a), and other randomized studies are still ongoing. However, among this patient population, it is still not clear who could benefit from extended therapy and what the optimal treatment duration should be. New multigene assays such as EndoPredict, PAM50 ROR-score, HOXB13/IL17BR ratio and Breast Cancer Index provide significant and relevant prognostic information concerning the likelihood of recurrence beyond 5 years after surgery. The identified low-risk subgroups not only show a very favorable prognosis, they also seem to have only little benefit from extended aromatase inhibitor therapy. Many of these reverse transcriptase/polymerase chain reaction-based techniques have been validated in archived tumor material from large phase III trials, and will soon be available to routine pathology laboratories as an aid in clinical decision-making for patients.
    Breast Care 05/2014; 9(2):97-100. DOI:10.1159/000362482 · 0.63 Impact Factor
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    ABSTRACT: Adjuvant cisplatin-based chemotherapy only marginally improves survival in patients with completely resected non-small-cell lung cancer (NSCLC). We have evaluated the predictive value of mutations in TP53, encoding the tumour suppressor p53, in the International Adjuvant Lung Cancer Trial (IALT), a randomized trial of adjuvant cisplatin-based chemotherapy against observation. TP53 (exons 4 to 8) was sequenced in 524 archived specimens of IALT patients with a median follow-up of 7.5 years. Predictive analyses were based on Cox models adjusted for clinical and pathological variables. P-values ≤ 0.01 were considered as significant. Mutations were detected in 221 patients (42%) and had no predictive value for the effect of chemotherapy (interaction between TP53 and treatment: p=0.17 for Overall Survival (OS); p=0.06 for Disease-Free Interval, (DFS)). However, among patients with mutations, outcome appeared worse in treatment compared to observation arms (HR for OS= 1.36 (95%CI [0.97-1.31), p=0.08; DFS= 1.40 (95%CI [1.01-1.95]), p= 0.04). When grouping mutations into classes according to predicted effects on protein structure, the tendency towards worse outcomes was restricted to “structure” mutations affecting residues of the hydrophobic core that are not located at the p53 protein-DNA interface (HR for death in this class vs wild-type T53 = 1.66; 95% CI [1.10-2.52], p=0.02). Overall, TP53 mutations are not significant predictors of outcome in this trial of cisplatin-based chemotherapy, although a specific class of structural mutations may be associated with a tendency towards worse outcomes upon treatment.
    Molecular oncology 05/2014; 8(3). DOI:10.1016/j.molonc.2013.12.015 · 5.33 Impact Factor

Publication Stats

4k Citations
975.15 Total Impact Points


  • 1996-2015
    • University of Vienna
      • • Institute of Social Medicine
      • • Clinic for Internal Medicine I
      • • Department of Internal Medicine III
      Wien, Vienna, Austria
    • Medical University of Vienna
      • • Institute for Cancer Research
      • • Department of Medicine I
      • • Clinical Division of Oncology
      • • Institute for Social Medicine
      Wien, Vienna, Austria
  • 2009
    • Institut Català d'Oncologia
      Barcino, Catalonia, Spain
  • 2007
    • University of Patras
      Rhion, West Greece, Greece
  • 2005
    • Karl-Franzens-Universität Graz
      Gratz, Styria, Austria