S Störkel

Universität Witten/Herdecke, Witten, North Rhine-Westphalia, Germany

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Publications (151)409.38 Total impact

  • S Störkel
    Der Urologe 10/2004; 43 Suppl 3:S118-9. DOI:10.1007/s00120-004-0593-7 · 0.44 Impact Factor
  • S Störkel · W Thoenes · G H Jacobi · R Lippold
    Aktuelle Urologie 03/2004; 35(1):18-21. DOI:10.1055/s-2004-822932 · 0.16 Impact Factor
  • Source
    C Rakozy · G E Schmahl · S Bogner · S Störkel
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    ABSTRACT: The current classification system of renal tumors is based on morphologic criteria, as supported by genetic findings. We present a group of previously unclassified tumors with similar morphologic and genetic features, suggesting a new entity within renal neoplasms. Seven renal tumors from five patients (ages 31-67 years) were analyzed. All cases were stained with periodic acid-Schiff, Hale's colloidal iron (HCI), and Alcian blue (AB) at pH 2.5/1.0 with and without hyaluronidase (HA) digestion. Immunohistochemical (IHC) stains were performed for CK8, CK18, CK19, vimentin, villin, Tamm-Horsfall protein (THP), renal cell carcinoma marker (RCC), epithelial membrane antigen (EMA), ulex europaeus agglutinin (UEA-1), soy bean agglutinin (SBA), peanut agglutinin (PNA), and MIB-1. Comparative genomic hybridization (CGH) and loss of heterozygosity (LOH) studies were performed on all cases. All tumors showed circumscribed growth, a tubular growth pattern with focal solid areas, no significant nuclear atypia and absence of necrosis, desmoplasia, or inflammation. Abundant extracellular mucin was present. Immunohistochemistry stains support collecting duct origin (EMA+, PNA+, SBA+/-, CK 8/18/19+, vimentin+/-, UEA-1-, RCC-, villin-, THP-). The proliferative rate was low (<1%). CGH showed multiple consistent chromosomal losses (-1,-4, -6, -8, -9, -13, -14, -15, -22). Clinical outcome was favorable, with recurrences but no known distant metastases or death of disease. These findings are distinct from all previously classified renal neoplasms. Our data suggest the presence of a unique tumor entity within tumors of probable collecting duct origin: tubular-mucinous renal tumors of low malignant potential.
    Modern Pathology 11/2002; 15(11):1162-71. DOI:10.1097/01.MP.0000031709.40712.46 · 6.19 Impact Factor
  • S Störkel
    Verhandlungen der Deutschen Gesellschaft für Pathologie 02/2002; 86:28-39.
  • M Velickovic · B Delahunt · S Störkel · S K Grebem
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    ABSTRACT: Deletions involving 3p are believed to be typical for conventional (clear cell) renal cell carcinoma (cRCC), with confirmed and suspected targets being the VHL and FHIT tumor suppressor genes, respectively. By contrast, 3p deletions are felt to be rare in papillary RCC (pRCC) and chromophobe RCC (chRCC); however, this belief is based on relatively scant data. In particular, 3p14.2 deletions, possibly resulting in FHIT inactivation, have been rarely studied in pRCC or chRCC even though they may be relevant in early renal tumorigenesis. We therefore examined 3p deletion rates and patterns in pRCC and chRCC with particular attention to 3p14.2. We examined 16 chRCCs and 27 pRCCs for loss of heterozygosity (LOH) at 3p25-26 and 3p14.2 using 13 well-mapped microsatellite markers. Those pRCC with LOH at 3p25-26 were also screened for VHL gene mutations. The results were correlated with tumor histology and patient outcome and compared with data we had obtained previously on cRCC. We found similar overall 3p LOH rates in pRCC (59%), chRCC (86.6%), and cRCC (75.8%). In pRCC and chRCC, LOH at 3p25-26 was more common than at 3p14.2, whereas the converse was true for cRCC. In the pRCC with 3p25-26 LOH, we confirmed that this was not associated with mutations of the VHL gene. At 3p14.2, LOH rates of pRCC were lower than those of cRCC and chRCC (p<0.02). All morphotypes showed a predominately interstitial LOH pattern, which was most pronounced in the 3p14.2 region in cRCC. 3p LOH in chRCC was associated with improved patient outcome, mirroring our previous cRCC data. We conclude that 3p LOH is a universal phenomenon in RCC, but has different underlying mechanisms, molecular targets, and implications in the different morphotypes, although FHIT inactivation may play a role in both cRCC and chRCC tumorigenesis.
    Cancer Research 06/2001; 61(12):4815-9. · 9.33 Impact Factor
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    ABSTRACT: Alpha-fetoprotein (AFP) is recognized as a tumor marker of yolk sac tumors, liver cancer and some other cancers of the digestive organs. Renal cell carcinoma (RCC) producing AFP is a rare entity. A case of AFP-producing RCC with solitary bone metastasis, but without liver involvement, is reported. The stain specific to AFP proved the presence of AFP in the cytoplasms of more cells of the renal tumors. Additionally, the other published cases are reviewed. These cases indicate that mesoderm-originating malignant tumors such as RCCs can produce AFP in some situations. So, AFP is probably more universal than believed, although it is generally a popular and useful tumor marker for hepatocellular carcinomas and yolk sac tumors.
    Urologia Internationalis 02/2001; 67(2):181-3. DOI:10.1159/000050982 · 1.43 Impact Factor
  • D Reutzel · M Mende · S Naumann · S Störkel · W Brenner · B Zabel · J Decker
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    ABSTRACT: Comparative genomic hybridization (CGH) has been applied to characterize 61 primary renal cell carcinomas derived histogenetically from the proximal tubulus. The tumor samples comprised 46 clear-cell renal cell carcinomas (ccRCCs) and 15 papillary renal cell carcinomas (pRCCs). Changes in the copy number of entire chromosomes or subregions were detected in 56 tumors (92%). In ccRCCs, losses of chromosome 3 or 3p (63%); 14q (30%); 9 (26%); 1 and 6 or 6q (17% each); 4 and 8 or 8p (15% each); 22 (11%); 2 or 2q and 19 (9% each); 7q, 10, 16, 17p, 18, and Y (7% each); and 5, 11, 13, 15, and 21 (4% each) were detected. Most frequent genomic gains in ccRCC were found on chromosome 5 (63%); 7 (35%); 1 or 1q (33%); 2q (24%); 8 or 8q, 12, and 20 (20% each); 3q (17%); 16 (15%); 19 (13%); 6 and 17 or 17q (11% each); and 4, 10, 11, 21, and Y (9% each). In pRCCs, gains in the copy number of chromosomes 7 and 17 (7/15, each) and 16 and 20 (6/15, each) were frequent. One pRCC showed amplification of subchromosome regions 2q22-->q33, 16q, 17q and the entire X chromosome. In pRCC, losses were less frequently seen than gains. Losses of chromosomes 1, 14, 15, and Y (3/15 each) and 2, 4, 6, and 13 (2/15 each) were observed. In ccRCCs, statistical evaluation revealed significant correlations of chromosomal imbalances with tumor stage and grade, i.e., a gain in copy number of chromosome 5 correlated positively with low tumor grade, whereas a gain of chromosomes 10 and 17 correlated positively with high tumor grade. Furthermore, loss of chromosome 4 correlated positively with high tumor stage.
    Cytogenetics and cell genetics 02/2001; 93(3-4):221-7. DOI:10.1159/000056987
  • B Seliger · Y Rongcun · D Atkins · S Hammers · C Huber · S Störkel · R Kiessling
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    ABSTRACT: The HER-2/neu oncoprotein, a 185 kDa membrane-associated tyrosine kinase with extensive homology to the epidermal growth factor receptor (EGF-R), is overexpressed in breast and ovarian carcinomas. Its overexpression is closely associated with poor prognosis in the course of disease. Here we demonstrate HER-2/neu overexpression in both established cell lines and biopsy material obtained from renal epithelial tumors. Immunohistochemical analysis of human kidney tumor lesions using 2 HER-2/neu-specific antibodies revealed HER-2/neu expression in more than 40% of primary epithelial renal tumors and more than 30% of primary renal cell carcinoma (RCC) specimens. A distinctive HER-2/neu expression pattern was found in different subtypes of kidney tumors with the highest frequency in chromophilic and chromophobic RCC, but neither associated with disease stage nor tumor grade. Eight of 10 RCC cell lines expressed significant levels of HER-2/neu mRNA and protein, but at a lower level compared with HER-2/neu overexpressing ovarian carcinoma cells. To evaluate the immune response against HER-2/neu expressing HLA-A2-positive (HLA-A2(+)) RCC cells, allogeneic HLA-A2-restricted cytotoxic T-lymphocyte (CTL) lines generated by pulsing dendritic cells with 3 different HER-2/neu-derived peptides, (HER-2(9.369), HER-2(9.435) and HER-2(9.689), were utilized in chromium-release assays. Specific lysis of HER-2/neu expressing HLA-A2(+) RCC cell lines was mediated by CTL lines specific for each of these 3 HER-2/neu-derived epitopes. The fine specificity of 2 CTL clones was defined to the epitopes HER-2(9.435) and HER-2(9.689). Their specificity was then confirmed by cold target inhibition assays. In addition, CTL-mediated lysis was enhanced by pulsing tumor cells with exogenous HER-2/neu-specific peptides. Our data suggest that (i) HER-2/neu is heterogeneously expressed in different subtypes of RCC, (ii) HER-2/neu is naturally processed by RCC and (iii) HER-2/neu epitopes presented by RCC can be recognized by HLA-A2-restricted, HER-2/neu-specific CTL.
    International Journal of Cancer 09/2000; 87(3):349-59. DOI:10.1002/1097-0215(20000801)87:3<349::AID-IJC7>3.0.CO;2-O · 5.09 Impact Factor
  • Source
    M J Maeurer · P Trinder · G Hommel · W Walter · K Freitag · D Atkins · S Störkel
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    ABSTRACT: Both antigen-presenting cells and immune effector cells are required to effectively eradicate or contain Mycobacterium tuberculosis-infected cells. A variety of cytokines are involved to ensure productive "cross talk" between macrophages and T lymphocytes. For instance, infection of macrophages with mycobacteria leads to effective interleukin-7 (IL-7) and IL-15 secretion, and both cytokines are able to maintain strong cellular immune responses of alpha/beta and gamma/delta T cells. Here we show that either cytokine is able to enhance survival of M. tuberculosis-infected BALB/c mice significantly compared to application of IL-2, IL-4, or phosphate-buffered saline (as a control). Enhanced survival could be achieved only when IL-7 or IL-15 was delivered as a treatment (i.e., 3 weeks postinfection), not when it was administered at the time of infection. Increased survival of M. tuberculosis-infected animals was observed following passive transfer of spleen cells harvested from M. tuberculosis-infected, IL-7- or IL-15-treated animals, but not after transfer of spleen cells obtained from mice which received either cytokine alone. Histological examination revealed that IL-7 and IL-15 failed to significantly impact on the number and composition of granulomas formed or the bacterial load. Our data indicated that administration of IL-7 or IL-15 to M. tuberculosis-treated animals resulted in a qualitatively different cellular immune response in spleen cells as reflected by increased tumor necrosis factor alpha and decreased gamma interferon secretion in response to M. tuberculosis-infected antigen-presenting cells.
    Infection and Immunity 06/2000; 68(5):2962-70. DOI:10.1128/IAI.68.5.2962-2970.2000 · 3.73 Impact Factor
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    ABSTRACT: To elucidate the role of somatic alterations for renal cancer etiology and prognosis, we analyzed 227 sporadic renal epithelial tumors for mutations and hypermethylations in the von Hippel-Lindau tumor suppressor gene VHL. Tumors were classified according to the recommendations of the Union Internationale Contre le Cancer (UICC) and the American Joint Committee on Cancer (AJCC). Somatic VHL mutations were identified by PCR, single-strand conformation polymorphism analysis, and sequencing, and hypermethylations were identified by restriction enzyme digestion and Southern blotting. Frequencies of VHL alterations were established, and an association with tumor type or tumor type and tumor stage was evaluated. VHL mutations and hypermethylations were identified in 45% of clear cell renal cell carcinomas (CCRCCs) and occasionally (3 of 28) in papillary (chromophilic) renal cell carcinomas (RCCs). Lack of VHL mutations and hypermethylations in chromophobe RCCs and oncocytomas was statistically significant (P = 0.0001 and P = 0.0004, respectively). RCCs carrying VHL alterations showed, in nine cases (12%), mutations at a hot spot involving a thymine repeat (ATT.TTT) in exon 2. Tumor staging was critical to the VHL mutation/hypermethylation detection rate in CCRCCs shown by separate evaluation of patients from medical centers in Munich, Heidelberg, and Mainz. The spectrum of pT1, pT2, and pT3 CCRCCs and the VHL mutation/hypermethylation detection rate varied among these three groups. Altogether, VHL alterations were significantly associated with pT3 CCRCCs (P = 0.009). This is the first evidence of frequent somatic VHL mutations at a particular site within exon 2 and an association of VHL mutations/hypermethylations with a standard prognostic factor.
    Cancer Research 05/2000; 60(7):1942-8. · 9.33 Impact Factor
  • S Störkel
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    ABSTRACT: The recent new morphological classification of epithelial renal tumors has overcome the former unspecified adenoma and carcinoma classification by introducing a specific subtyping. Today we divide in oncocytic and metanephrogenic renal cell adenomas, clear cell-, papillary-, chromophobe-, and collecting duct associated renal cell carcinomas, and transitional cell- and neuroendocrine renal carcinomas. These entities are characterized by a definite immunohistological marker spectrum and differing histogenetic pathways. New cytogenetic data have proven specific chromosomal aberrations for the different tumor types and have confirmed the morphological classification. Certain genetic changes are correlated to specific pathological phenotypes especially in oncocytic tumors. It is possible now to propose an in part hypothetical kidney tumor model which describes the development and progression of adenomas and carcinomas of the kidney in an adenoma-carcinoma sequence.
    Der Urologe 10/1999; 38(5):425-32. DOI:10.1007/s001200050310 · 0.44 Impact Factor
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    ABSTRACT: To investigate the histological and immunohistochemical behaviour of free buccal mucosa and full-skin grafts after exposure to urine. A buccal mucosal graft and a full-skin graft were freely transferred into the bladder of 12 minipigs, after stripping the bladder mucosa. Endoscopic investigations were carried out 2 and 5 months after surgery, and the grafts examined after death at 7 months, both histologically and immunohistochemically. Shrinkage of the full-skin graft was apparent endoscopically in five cases. Of the nine full-skin grafts, four showed severe inflammatory reactions, two necrosis and two ulcerations. Conversely, the 10 buccal mucosal grafts had fewer pathological findings (three minimal inflammation and three with scars) and a pronounced similarity on immunohistochemistry. The buccal mucosal graft showed significantly fewer adverse histopathological findings after long-term exposure to urine than the full-skin graft and is therefore a preferable material for urethral reconstruction.
    BJU International 08/1999; 84(1):108-11. DOI:10.1046/j.1464-410X.1999.00079.x · 3.53 Impact Factor
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    ABSTRACT: Tumors associated with the VHL (von Hippel-Lindau) disease, such as hemangioblastomas and renal carcinomas and their sporadic counterparts, are cystic and well vascularized. Mutations of the VHL tumor-suppressor gene and elevated levels of vascular endothelial growth factor (VEGF) have been described in these tumors. The upregulation of VEGF has been shown in vitro as a consequence of alteration of the VHL gene. No comprehensive in vivo analysis has yet been carried out of the factors affecting tumor growth, vascularization, VEGF, and VHL expression. We performed immunohistochemistry and mRNA studies on primary sporadic renal carcinomas and matching normal renal tissue. We semiquantitatively analyzed 29 renal carcinomas (22 clear cell, 5 chromophilic, 2 chromophobic tumors) for VHL mRNA, and VEGF expression for morphology and tumor size. Immunohistochemistry was carried out for VEGF protein expression, vascularization, and macrophage infiltration. Vascularization of the chromophilic renal carcinomas was lower than that of the clear cell type of renal carcinoma. Low VEGF protein expression was seen in four of the five chromophilic renal carcinomas. We found two groups of clear cell renal cell carcinoma: one with reduced VHL mRNA and increased VEGF mRNA, and the other without significantly altered VHL or VEGF mRNAs. Tumor vascularization was correlated with VEGF protein and seemed to be independent of macrophage infiltration. Our in vivo findings support the inverse relationship between the regulation of VHL and that of VEGF. Our data also indicate that there may be an VHL-independent pathway for the induction of tumor vascularization.
    Journal of Molecular Medicine 07/1999; 77(6):505-10. DOI:10.1007/s001099900022 · 5.11 Impact Factor
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    ABSTRACT: Human kidney proximal tubule epithelia express the ATP-dependent export pump for anionic conjugates encoded by the MRP2 (cMRP/cMOAT) gene (symbol ABCC2). MRP2, the apical isoform of the multidrug resistance protein, is an integral membrane glycoprotein with a molecular mass of approximately 190 kD that was originally cloned from liver and localized to the canalicular (apical) membrane domain of hepatocytes. In this study, MRP2 was detected in human kidney cortex by reverse transcription-PCR followed by sequencing of a 826-bp cDNA fragment and by immunoblotting using two different antibodies. Human MRP2 was localized to the apical brush-border membrane domain of proximal tubules by double and triple immunofluorescence microscopy including laser scanning microscopy. The expression of MRP2 in renal cell carcinoma was studied by reverse transcription-PCR and immunoblotting in samples from patients undergoing tumor-nephrectomy without prior chemotherapy. Clear-cell carcinomas, originating from the proximal tubule epithelium, expressed MRP2 in 95% (18 of 19) of cases. Immunofluorescence microscopy of MRP2 in clear-cell carcinoma showed a lack of a distinct apical-to-basolateral tumor cell polarity and an additional localization of MRP2 on intracellular membranes. MRP2, the first cloned ATP-dependent export pump for anionic conjugates detected in human kidney, may be involved in renal excretion of various anionic endogenous substances, xenobiotics, and cytotoxic drugs. This conjugate-transporting ATPase encoded by the MRP2 gene has a similar substrate specificity as the multidrug resistance protein MRP1, and may contribute to the multidrug resistance of renal clear-cell carcinomas.
    Journal of the American Society of Nephrology 07/1999; 10(6):1159-69. · 9.34 Impact Factor
  • Article: Retraction.
    Cancer Research 05/1999; 59(8):2021. · 9.33 Impact Factor
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    ABSTRACT: The production of metastases depends on changes in a large number of genes. It is also connected with the interaction of tumor cells with the environment. It has been reported that primary tumor clone domination is also an important factor in metastasizing, and in many neoplasms dominating clones are the metastatic forerunners. Up to now it is unknown whether domination of a given clone in a primary renal cell carcinoma is a crucial factor in forming metastases or rather presence or absence of specific genes imposes the major advantage in the metastatic process. To study the presence or absence of the duplication and mitotic nondisjunction event as one of the phenomenon in the creation of metastases, as well as possible derivation of metastatic cells from the minor subclone of primary tumor, we examined three metastatic renal clear-cell carcinomas in which by comparative genomic hybridization we detected the loss of 3p in the primary tumor and two copies of 3p in the corresponding metastasis. Loss of heterozygosity analyses using markers for 3p25 (D3S1038), 3p21.1 (D3S1295), and 3p14.2 (D3S1481) proved heterozygosity of at least two 3p loci in all metastatic tumors, which indicates the absence of mitotic nondisjunction event as a cause of occurrence of two copies of 3p in metastases. Our results suggest that in some of the clear-cell renal carcinomas metastatic cells may derive from minor subclones of primary tumors.
    Cancer Detection and Prevention 02/1999; 23(6):479-84. DOI:10.1046/j.1525-1500.1999.99056.x · 2.52 Impact Factor
  • A. Kollias · V. Poulakis · U. Witzsch · E. Becht · S. Störkel
    Aktuelle Urologie 01/1999; 30(3):199-203. DOI:10.1055/s-1999-13320 · 0.16 Impact Factor
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    ABSTRACT: We analyzed familial renal oncocytoma to provide a foundation for studies aimed at defining genes involved in the pathogenesis of renal oncocytoma. We describe 5 families with multiple members affected with renal oncocytoma. Tumors were analyzed pathologically, and affected and nonaffected members were screened clinically and genetically. We identified 12 affected male and 3 affected female (ratio 4:1) individuals in the 5 families. In affected family members renal oncocytomas were often multiple and bilateral. No metastatic disease was observed. Most renal oncocytomas were detected incidentally in asymptomatic individuals or during screening of asymptomatic members of renal oncocytoma families. One identical twin pair was affected with bilateral multiple renal oncocytomas. Renal oncocytoma may be inherited in some families.
    The Journal of Urology 09/1998; 160(2):335-40. DOI:10.1016/S0022-5347(01)62888-X · 4.47 Impact Factor
  • Cancer Genetics and Cytogenetics 08/1998; 104(1):74-6. DOI:10.1016/S0165-4608(97)00434-2 · 1.93 Impact Factor
  • H. J. Decker · S. Störkel
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    ABSTRACT: Nierenzellkarzinome zeichnen sich durch einen hohen Grad an klinischer und tumorbiologischer Heterogenität aus. Bei deutlicher Zunahme der Erkrankungszahlen in Europa und den USA und bei nahezu unveränderter Therapie- refraktärität des metastasierten Tumors, bleibt das Nierenzellkarzinom eine Herausforderung für den Kliniker und den Tumorforscher [1]. Die anfänglich hohen Erwartungen, die in die immun-modulatorische Therapie gesetzt worden waren, haben sich bei bekannter Unempfindlichkeit gegenüber Strahlen- und Chemotherapie nicht erfüllt [2]. Neue therapeutische Konzepte erscheinen somit notwendig. In diesem Review wird die neue Klassifikation der epithelialen Nierentumoren dargestellt und auf die wesentlichen genetischen und molekularen Aberrationen, sowie deren mögliche diagnostische Bedeutung eingegangen.
    Der Onkologe 01/1998; 4(3):214-220. DOI:10.1007/s007610050194 · 0.14 Impact Factor

Publication Stats

4k Citations
409.38 Total Impact Points


  • 1996–2002
    • Universität Witten/Herdecke
      • Institute of Physiology and Pathophysiology
      Witten, North Rhine-Westphalia, Germany
  • 1996–1997
    • University of Münster
      • Gerhard-Domagk-Institute of Pathology
      Muenster, North Rhine-Westphalia, Germany
  • 1993–1997
    • University of Groningen
      • Department of Medical Genetics
      Groningen, Province of Groningen, Netherlands
  • 1984–1997
    • Johannes Gutenberg-Universität Mainz
      • • Department of Urology
      • • Klinik und Poliklinik für Unfallchirurgie
      • • Division of Medical Biometry I
      • • Institute of Pathology
      Mayence, Rheinland-Pfalz, Germany
  • 1995
    • Technische Universität München
      München, Bavaria, Germany
    • Universitätsklinikum Düsseldorf
      Düsseldorf, North Rhine-Westphalia, Germany