L Füzesi

Georg-August-Universität Göttingen, Göttingen, Lower Saxony, Germany

Are you L Füzesi?

Claim your profile

Publications (234)579.75 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: We have previously described immune cells in untreated primary gastrointestinal stromal tumors (GIST). Here we compare immune cells in metastatic and primary GIST, and describe their chemoattractants. For this purpose, tissue microarrays from 196 patients, 188 primary and 51 metastasized GIST were constructed for paraffin staining. Quantitative analysis was performed for cells of macrophage lineage (Ki-M1P, CD68), T-cells (CD3, CD56) and B-cells (CD20). Chemokine gene-expression was evaluated by real-time RT-PCR. Immuno-localisation was verified by immunofluorescence. Ki-M1P+ cells were the predominant immune cells in both primary and metastatic GIST (2 8.8% ± 7.1, vs. 26.7% ± 6.3). CD68+ macrophages were significantly fewer, with no significant difference between primary GIST (3.6% ± 2.1) and metastases (4.6% ± 1.5). CD3+ T-cells were the most dominant lymphocytes with a significant increase in metastases (7.3% ± 2.3 vs. 2.2% ± 1.8 in primary GIST, P < 0.01). The percentage of CD56+ NK-cells was 1.1% ± 0.9 in the primary, and 2.4 ± 0.7 (P < 0.05) in the metastases. The number of CD20+ B-cells was generally low with 0.6% ± 0.7 in the primary and 1.8% ± 0.3 (P < 0.05) in the metastases. Analysis of the metastases showed significantly more Ki-M1P+ cells in peritoneal metastases (31.8% ± 7.4 vs. 18.2% ± 3.7, P < 0.01), whilst CD3+ T-cells were more common in liver metastases (11.7% ± 1.8 vs. 4.4% ± 2.6, P < 0.01). The highest transcript expression was seen for monocyte chemotactic protein 1 (MCP1/CCL2), macrophage inflammatory protein 1α (MIP-1α/CCL3) and the pro-angiogenic growth-related oncoprotein 1 (Gro-α/CXCL-1). Whilst the ligands were predominantly expressed in tumor cells, their receptors were mostly present in immune cells. This locally specific microenvironment might influence neoplastic progression of GIST at the different metastatic sites.
    International journal of clinical and experimental pathology. 01/2014; 7(7):3563-79.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Here, synchronous (early) and metachronous (late) brain metastasis (BM) events of sporadic ccRCC (n = 148) were retrospectively analyzed using comparative genomic hybridization (CGH). Using oncogenetic tree models and cluster analyses, chromosomal imbalances related to recurrence-free survival (RFS-BM) were observed. Losses at 9p and 9q appeared to be hallmarks of metachronous BM events, whereas an absence of detectable chromosomal changes at 3p was often associated with synchronous BM events. Correspondingly, k-means clustering showed that Cluster 1 cases generally exhibited low copy number chromosomal changes that did not involve 3p. Cluster 2 cases had a high occurrence of -9p/-9q (94–98%) deletions, while Cluster 3 cases had a higher frequency of copy number changes, including loss at chromosome 14 (80%). The higher number of synchronous cases in Cluster 1 was also associated with a significantly shorter RFS-BM compared to Clusters 2 and 3 (p = 0.02). Conversely, a significantly longer RFS-BM was observed for Cluster 2 versus Clusters 1 and 3 (p = 0.02). Taken together, these data suggest that metachronous BM events of ccRCC are characterized by loss of chromosome 9, whereas synchronous BM events may form independently of detectable genetic changes at chromosomes 9 and 3p.
    Cancer Genetics. 01/2014;
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: PURPOSE: The duodenum as primary site for gastrointestinal stromal tumors (GISTs) is rare and mitotic rate, tumor size, type of mutation and number of chromosomal aberrations have prognostic implications. METHODS: We analyzed the outcome of 13 patients with duodenal GISTs who underwent surgical tumor resection. Either segmental duodenectomy or pylorus-preserving duodenopancreatectomy was performed. The tumors were histopathologically examined and the risk of progression was assessed based on tumor size and mitotic count. Additionally, mutation analysis of the KIT and PDGFRA receptor tyrosine kinase genes and comparative genomic hybridization (CGH) were performed in all cases. RESULTS: Eight patients underwent segmental duodenectomy and five patients were treated with pylorus-preserving duodenopancreatectomy. None of the five GISTs with low or no risk for malignancy according to the Miettinen classification developed tumor progress. In contrast, five of eight cases (62.5%) with high-risk tumors revealed tumor progress, and four of these patients died (50%). The median overall survival for all patients was 66 months, and the median disease-free survival 41 months. The operative procedure and type of mutation did not correlate with long-term survival. CGH analysis displayed -15q in 12/13 tumors, and -1p in 11/13 cases as characteristic chromosomal aberrations for intestinal origin. Notably, -22q was present in three of four cases with tumor progress. CONCLUSIONS: Both segmental duodenectomy and pylorus-preserving duodenopancreatectomy are appropriate options to treat duodenal GIST and should be implemented depending on resectability and the patient's performing state. The Miettinen classification and CGH findings correlate with the clinical course.
    International Journal of Colorectal Disease 02/2012; · 2.24 Impact Factor
  • BJU International 02/2012; 109(4):640-4. · 3.05 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Adenocarcinoma of the small intestine arising from heterotopic gastric mucosa is extremely rare. In this report, we present the case of a 68-year-old woman who complained of abdominal pain, weight loss and subileus. Gross examination of resected small bowel revealed multiple flat polypous lesions with cysts in the ileal submucosa, one of which containing an ulcerated, stenosing tumour. On microscopic examination, an adenocarcinoma of the ileum arising from multifocal gastric heterotopia with secondary gastritis cystica profunda was diagnosed. Comparative genomic hybridization of the adenocarcinoma revealed chromosomal gains at 1q, 3q, 5p, 8q, 11p, 12p, 13q and losses at Xp, 4q, 8p, 10p, 14q, 17p, 20p, compatible with a high degree of genomic instability.
    Medical Oncology 12/2011; 28(4):1023-6. · 2.14 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Non-small cell lung cancer (NSCLC) is one of the most aggressive tumors, with a very low overall survival rate. We investigated surgically resected squamous cell carcinoma (SCC) and adenocarcinoma (AC) to identify chromosomal imbalances and their value for individual prognostication. A total of 80 cases, including 55 SCC and 25 AC, were retrospectively analyzed by comparative genomic hybridization. To model the sequential cytogenetic events, an oncogenetic tree model was applied based on maximum likelihood estimation. Clinicopathologic data and follow-up data were correlated with chromosomal imbalances. Fifty-one percent of patients were in stage I, 32% in stage II, and 17% in stage III, without statistically significant differences in staging distribution between SCC and AC. The average number of copy number imbalances was higher in SCC than in AC (9.4±1.2 vs 5.4±1.1; p=0.11). Frequency of chromosomal imbalances at -3p, +3q, -4q, +5q, -5q, +7q, and -13q were significantly different between SCC and AC. Subsequently, oncogenetic tree modeling identified different clusters of chromosomal imbalances for SCC and AC. Appearance of the -3p-cluster in SCC was associated with decreased overall survival independent of clinicopathologic parameters (mean, 42.8±7.5 months vs 80.1±9.1 months, log rank p=0.019), whereas in AC no prognostic value could be identified for specific clusters of chromosomal imbalances. Although, the limited number of analyzed cases allows a cautious statement on chromosomal imbalances, the oncogenetic tree modeling suggests distinct patterns of cytogenetic evolution for SCC and AC with implications for clinical outcome in SCC.
    The Annals of thoracic surgery 09/2011; 92(3):1038-43. · 3.45 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Basaloid squamous cell carcinoma (BSCC) and carcinosarcoma of the esophagus are rare entities, making up fewer than 2% of esophageal malignancies. Comparative genomic hybridization (CGH) in 1 case of BSCC and 2 cases of carcinosarcoma and subsequent array CGH in 1 case each of BSCC and carcinosarcoma revealed common chromosomal gains at 2p25.3-2p12, 7q21.3-7q22.3, and 11q13.2-11q13.4. Chromosomal losses at 13q31qter were observed in both carcinosarcomas. In addition, progression of genomic instability from in situ to invasive carcinosarcoma could be demonstrated by using array CGH. Our observations suggest a common genetic origin of BSCC and carcinosarcoma.
    American Journal of Clinical Pathology 04/2011; 135(4):579-86. · 2.88 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Primary papillary tumors of the central nervous system and particularly the pineal region are rare. Papillary tumor of the pineal region (PTPR) is a recently described neoplasm that has been formally recognized in the 2007 World Health Organization Classification of Tumors of the Nervous System. Because of their rarity, further pheno- and genotypical observations as well as therapeutic experience are necessary to differentiate PTPR from other primary or secondary papillary tumors of this region. We herein present three cases of PTPR characterized by local recurrence in two of them. Primary and recurrent tumors were analyzed by immunohistochemistry and comparative genomic hybridization (CGH). From our results clonal chromosomal aberrations can be postulated which seem to be a feasible tool to differentiate PTPRs from other primary or secondary papillary tumors of this region.
    Brain Pathology 04/2011; 21(6):672-7. · 4.74 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Pulmonary metastases (PM) are frequent in colorectal carcinoma (CRC). However, little is known about the chromosomal imbalances in CRC that accompany metastatic pulmonary disease. We investigated tumor specimens of CRC (n=30) and their corresponding PM by comparative genomic hybridization (CGH). There were no substantial differences in the degree of chromosomal instability between CRC and PM, neither in average number of copy alterations (ANCA; 6.6 ± 0.8 and 7.7 ± 0.9) nor in gains (2.6 ± 0.5 and 2.6 ± 0.4), losses (3.6 ± 0.5 and 4.8 ± 0.6), or amplifications (0.4 ± 0.1 and 0.3 ± 0.1). Basically, similar patterns of chromosomal imbalances could be identified in both CRC and corresponding PM, most frequently including chromosomal gains at 7, 8q, 13q, and 20q, as well as losses at 4, 8p, 18q, and 20p. CRC and corresponding PM differed in frequencies for losses at chromosome arm 5q (3 vs. 26%; P=0.012). Losses at 4q and 11q in CRC were significantly associated with lower 5-year survival rates (80 vs. 24%, P=0.026 and 74 vs. 17%, P=0.007, respectively), and they may represent candidates for adverse prognostic markers in primary CRC.
    Cancer Genetics 03/2011; 204(3):122-8. · 1.92 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In gastrointestinal stromal tumors (GISTs), the occurrence of an epithelioid/mixed phenotype has been correlated to PDGFRA mutations, gastric localization and favorable outcome. On the other hand, the prognostic significance of an epithelioid/mixed growth pattern occasionally observed in GISTs with KIT mutation is unclear. The aim of this study was to evaluate the prognostic significance of an epithelioid/mixed phenotype in correlation to anatomical localization, genotype, and expression of cell-cycle markers in a series of 116 primary GISTs with KIT mutation on a tissue microarray. Independent of their anatomical localization, the majority of KIT-mutated GISTs displayed a pure spindled phenotype (72%), with the remaining tumors showing an epithelioid/mixed growth pattern. In KIT-mutated GISTs from the stomach, the occurrence of an epithelioid/mixed growth pattern was significantly correlated with larger tumor diameters (P=0.005), higher mitotic counts (P=0.0001), high-risk category (P=0.001), higher expression of the G2-phase cell-cycle marker cyclin B1 (P=0.04), higher expression of the G1 to M-phase proliferation marker Ki67 (P=0.02) and a significantly shorter disease-free survival (P=0.003) compared with tumors with pure spindled morphology. In contrast, there were no significant differences between pure spindled and epithelioid/mixed GISTs from the small/large bowel. Our findings indicate that the epithelioid/mixed phenotype in KIT-mutant gastric GISTs represents a secondary tumor growth pattern associated with tumor progression and adverse outcome, probably through accelerated G1/S-phase restriction point passage.
    Modern Pathology 02/2011; 24(2):248-55. · 5.25 Impact Factor
  • Journal of Urology - J UROL. 01/2011; 185(4).
  • Cancer genetics and cytogenetics 12/2010; 203(2):341-4. · 1.54 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: For living-donor liver transplantation (LDLT) it is of paramount importance to preserve as much viable liver tissue as possible to avoid postoperative complications in the donor and recipient. The depth of tissue damage caused by common surgical techniques for liver resection has not been studied so far. Here we compared the depth of tissue damage and the immunohistochemical expression of heat shock protein (HSP) 70, a marker for tissue damage, in a porcine model of liver resection, to assess the effect of different surgical techniques, i.e., blunt dissection (BD), and dissection with an ultrasound aspirator (UA), an ultrasound scalpel (US), or a water-jet (WJ). Analysis with linear mixed effects models (LME) showed significantly less tissue damage with BD and UA than with US and WJ (joint p value <0.001). Damage also increased within 6 h after surgery (p value = 0.004). Semiquantitative evaluation of HSP 70 showed increased expression after resection with US compared to all other resection methods (p value <0.001), indicating increased tissue damage with this method. We suggest that in cases of liver resection for LDLT surgeons should reevaluate using US and WJ because of possible excessive tissue damage compared to BD and UA. Overall we advocate the use of BD as it requires no special equipment and, hence, has considerably higher cost-effectiveness without compromising tissue preservation and clinical outcome and is readily available even in low-tech environments.
    Journal of hepato-biliary-pancreatic sciences. 12/2010; 18(3):436-42.
  • [Show abstract] [Hide abstract]
    ABSTRACT: In inflammatory bowel disease refractory to established therapies, treatment with biological agents such as monoclonal tumor necrosis factor-α antibodies is an established therapeutic option. However, application in renal allograft recipients is either not licensed or has not yet been systematically examined. Herein, we present 2 case reports of renal allograft recipients who had steroid-refractory ulcerative colitis who demonstrated improvement of symptoms after treatment with infliximab, without signs of effect on transplant function. In both patients, stool frequency decreased significantly. Colonoscopy controls and histologic examination after initiation of treatment revealed a state of remission. Renal function parameters and drug concentrations remained constant.
    Transplantation Proceedings 11/2010; 42(9):3880-2. · 0.95 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To identify new mediators of cardiac hypertrophy, we performed a genome-wide mRNA screen of stretched neonatal rat cardiomyocytes (NRCMs). In addition to known members of the hypertrophic gene program, we found the novel sarcomeric Z-disc LIM protein Lmcd1/Dyxin markedly upregulated. Consistently, Lmcd1 was also induced in several mouse models of myocardial hypertrophy suggesting a causal role in cardiac hypertrophy. We overexpressed Lmcd1 in NRCM, which led to cardiomyocyte hypertrophy and induction of the hypertrophic gene program. Likewise, the calcineurin-responsive gene RCAN1-4 was found significantly upregulated. Conversely, knockdown of Lmcd1 blunted the response to hypertrophic stimuli such as stretch and phenylephrine (PE), suggesting that Lmcd1 is required for the hypertrophic response. Furthermore, PE-mediated activation of calcineurin was completely blocked by knockdown of Lmcd1. To confirm these results in vivo, we generated transgenic mice with cardiac-restricted overexpression of Lmcd1. Despite normal cardiac function, adult transgenic mice displayed significant cardiac hypertrophy, again accompanied by induction of hypertrophic marker genes such as ANF and alpha-skeletal actin. Likewise, Rcan1-4 was found upregulated. Moreover, when crossed with transgenic mice overexpressing constitutionally active calcineurin, Lmcd1 transgenic mice revealed an exacerbated cardiomyopathic phenotype with depressed contractile function and further increased cardiomyocyte hypertrophy. We show that the novel z-disc protein Lmcd1/Dyxin is significantly upregulated in several models of cardiac hypertrophy. Lmcd1/Dyxin potently induces cardiomyocyte hypertrophy both in vitro and in vivo, while knockdown of this molecule prevents hypertrophy. Mechanistically, Lmcd1/Dyxin appears to signal through the calcineurin pathway. Lmcd1/Dyxin may thus represent an attractive target for novel antihypertrophic strategies.
    Journal of Molecular and Cellular Cardiology 10/2010; 49(4):673-82. · 5.15 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To identify new interactions as well as diagnostically, prognostically and therapeutically relevant differences in the regulation of gene expression in gastrointestinal stromal tumors (GISTs), we analyzed the methylation status, mRNA expression, microRNA expression, protein expression and protein phosphorylation in parallel in identical tumor tissue samples. The data were analyzed in a multilayer approach and were correlated to each other and to clinico-pathological parameters. Differentially regulated genes were mapped to signal transduction pathways which are already known to play a major role in GISTs. A functionally orientated overview of the different data layers was constructed, which enabled new insights into gene regulation in GISTs.
    Der Pathologe 10/2010; 31 Suppl 2:134-7. · 0.62 Impact Factor
  • Cancer genetics and cytogenetics 07/2010; 200(2):194-7. · 1.54 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Krukenberg tumor is a well-known ovarian metastasis, usually of gastric signet ring cell carcinoma in female patients. Although gastric carcinoma is more frequent in men, to our knowledge, only few cases of counterpart testicular metastases have been described as yet. We report a 64-year-old patient who complained of right testicular pain. Right-sided orchiectomy was performed, and metastatic signet ring cell carcinoma of spermatic cord and testis was diagnosed through histological examination and immunohistochemistry. The following stomach biopsy confirmed the primary signet ring cell carcinoma in the stomach. This extremely rare form of metastatic dissemination resembles the Krukenberg tumor of ovaries. Immunohistochemical staining plays an important role in the differential diagnosis of spermatic cord enlargement.
    Pathology - Research and Practice 07/2010; 206(7):519-21. · 1.21 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Information on structural chromosomal changes in brain metastases (BM) of colorectal carcinoma (CRC) is very limited. Therapeutic and diagnostic strategies to reduce the risk of BM have potential impact on cancer mortality. By using comparative genomic hybridization, the primary CRC of 11 patients and their corresponding 13 BM were analyzed. BM showed significantly more mean chromosomal aberrations than the primary CRC (13.6+/-2.1 vs. 7.9+/-1.9, P=0.03), significantly more chromosomal gains (7.2+/-0.9 vs. 3.5+/-0.9, P=0.01), and tended to have also more losses (6.1+/-1.4 vs. 4.0+/-1.1, P=0.29). Changes that occurred significantly more often in BM than in primary CRC were gains of 8q, 12p, 12q, and 20p, as well as losses of 5q. BM of CRC show a significantly higher chromosomal instability in comparison to primary tumors. The prevalently altered genomic regions in the metastases of this study are likely to harbor genes that play an important role in the genesis of brain-specific metastasis.
    Cancer genetics and cytogenetics 04/2010; 198(1):47-51. · 1.54 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We report a case of a 27-year-old female with thrombotic microangiopathy as an initial presentation of an unexpected disseminated gastric carcinoma. Based on clinical features and laboratory findings, thrombotic thrombocytopenic purpura (TTP) was diagnosed and plasma exchange started. However, she had responded poorly to plasmapheresis, developed multiorgan failure and died 72 h after admission. Autopsy revealed a disseminated gastric adenocarcinoma with metastatic infiltration of dura mater and disseminated tumor cell emboli in the microcirculation of the liver and lungs. Genetic analysis revealed amplification of KRAS oncogene and aberrations in DCC tumor suppressor gene, which can explain the young age and advanced disease at presentation. The role of plasmapheresis in cancer-associated TTP is uncertain. Plasmapheresis delivers fresh coagulation factors and may theoretically promote microthrombi formation and lead to worsening of the disease. Thrombotic thrombocytopenic purpura seems to be a late and prognostically poor manifestation of an underlying malignancy, with majority of patients dying soon after diagnosis. It is important to be aware of this possibility in thrombotic microangiopathy, especially with atypical features and poor response to standard treatment.
    Therapeutic apheresis and dialysis: official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy 04/2010; 14(2):222-5. · 1.53 Impact Factor

Publication Stats

3k Citations
579.75 Total Impact Points

Institutions

  • 2000–2014
    • Georg-August-Universität Göttingen
      • Center for Biochemistry and Molecular Cell Biology
      Göttingen, Lower Saxony, Germany
  • 1999–2010
    • Universitätsmedizin Göttingen
      • • Department of Neurosurgery
      • • Department of Pathology
      • • Department of Gastroenterology and Endocrinology
      • • Department of Radiotherapy and Radiation Oncology
      • • Department of General, Visceral and Child Surgery
      • • Center for Physiology and Pathophysiology
      Göttingen, Lower Saxony, Germany
    • Semmelweis University
      Budapeŝto, Budapest, Hungary
  • 1991–2009
    • RWTH Aachen University
      • • Institute of Pathology
      • • Klinik für Diagnostische und Interventionelle Radiologie
      • • Klinik für Allgemein-, Viszeral- und Transplantationschirurgie
      • • Neurochirurgische Klinik
      Aachen, North Rhine-Westphalia, Germany
  • 2007
    • Uludag University
      • Department of Medical Genetics
      Bursa, Bursa, Turkey
    • University Hospital Merkur
      Zagrabia, Grad Zagreb, Croatia
  • 2006
    • University of Bonn
      Bonn, North Rhine-Westphalia, Germany
    • HELIOS Albert-Schweitzer-Klinik Northeim
      Northeim, Lower Saxony, Germany
  • 2005
    • University of Hamburg
      • Department of Urology
      Hamburg, Hamburg, Germany
  • 2004
    • Max Planck Institute of Molecular Cell Biology and Genetics
      Dresden, Saxony, Germany
  • 2003
    • Max Planck Institute for Molecular Genetics
      • Department of Computational Molecular Biology
      Berlin, Land Berlin, Germany
  • 1992–2001
    • University Hospital RWTH Aachen
      • Department of Neurology
      Aachen, North Rhine-Westphalia, Germany
  • 1996
    • University of Münster
      Muenster, North Rhine-Westphalia, Germany
    • Ruhr-Universität Bochum
      • Institut für Pathologie
      Bochum, North Rhine-Westphalia, Germany