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Hamburg, Germany

Friedrich R.E.,University of Hamburg | Dilcher J.,University of Hamburg | Jaehne M.,University of Hamburg | Loning T.,Albertinen Hospital
Anticancer Research | Year: 2012

PLAG1 mutations are related to the development of pleomorphic adenomas. A specific aspect of PA is the histological diversity of this entity, containing cells with mesenchymal, epithelial and myoepithelial differentiation. Evidence for myoepithelial cells in PA raises the question whether the very rare entity of pure myoepithelial salivary gland tumours shows chromosomal translocations and rearrangements and whether activation of PLAG1 can be detected. Materials and Methods: Fluorescence in-situ hybridisation (FISH) was established using the DNA-probes PLAG 233, PLAG 234, PLAG 235. The probes were generated from plasmids. Standardization of FISH was achieved in human lymphocytes. Routinely formalin-fixed, paraffin-embedded slices of myoepithelial salivary gland tumours were available for study. In some cases isolated nuclei were investigated. Isolation of the nuclei was performed according to Hedley. Scoring of the FISH was done with a Laser-scanning microscope (spot-counting: fluorescence signals/100 cells/slice). The number of signal variants was determined. All evaluated regions were registered on microphotographs. Results: PLAG1 was only rarely detected. PLAG1 is evidently not involved in the development of myoepithelial tumours. The proportion of 8q12-alterations in myoepithelial tumours was very low. Conclusion: PLAG1 is an insufficient marker to differentiate between benign and malignant myoepithelial tumours. Source

Ruf C.G.,Helmut Schmidt University | Ruf C.G.,University of Hamburg | Isbarn H.,University of Hamburg | Wagner W.,Helmut Schmidt University | And 3 more authors.
Urologic Oncology: Seminars and Original Investigations | Year: 2014

Objectives: Testicular germ cell tumors (GCTs) have their incidence peak in the third and fourth decades of life. Histologically, GCTs comprise of seminoma and nonseminoma at almost equal proportions with a slight preponderance of nonseminoma in most of the major series. Since decades, there is a shift toward decreasing age at presentation. Recently, there are suggestions of a reversal of the age trend, and also, the histologic subtype ratio appears to shift toward seminoma. We retrospectively looked to our patient populations to verify these recent trends. Methods: A total of 2,482 patients with histologically proven GCT diagnosed between 1976 and 2010 were retrospectively evaluated regarding the year of diagnosis, histology of primary tumor, and age at presentation. Patients were categorized according to the following time periods of treatment: before 1990, 1990 to 1994, 1995 to 1999, 2000 to 2004, and 2005 to 2010. Mean age and relative proportion of seminoma were compared among patient categories by employing the chi-square test and analysis of variance, respectively. Results: The mean age significantly increased from 28 to 36 years. The age difference between the 2 histologic subtypes remained constant between 6 and 8 years during the entire observation period. The relative proportion of seminoma continuously increased from 30.9% to 56% (P <0.001). Conclusion: There is evidence of a significant shift toward older age at diagnosis of GCT. In addition, the proportion of seminoma is constantly increasing at the expense of nonseminoma. The reasons for these developments are obscure. However, 2 old theories regarding the pathogenesis of GCT may receive support from our results: first, the theory of divergent pathogenetic pathways of seminoma and nonseminoma and second, the involvement of postnatal environmental factors in the pathogenesis of GCTs. © 2014 Elsevier Inc. Source

Woelber L.,University of Hamburg | Kress K.,University of Hamburg | Kersten J.F.,University of Hamburg | Choschzick M.,University of Hamburg | And 9 more authors.
BMC Cancer | Year: 2011

Background: Carbonic anhydrase IX (CAIX) is a membranous expressed metalloenzyme involved in pH homeostasis and cell adhesion. The protein is overexpressed in a variety of tumors and potentially associated with negative outcome. This study was designed to investigate the prognostic role of CAIX in serum and tumor tissue of patients with primary cervical cancer.Methods: Tumor samples of 221 consecutive patients with primary cervical cancer who underwent surgery between 1993 and 2008 were analyzed for CAIX expression by immunohistochemistry. Additionally, preoperative serum CAIX concentrations were determined by ELISA in a subset of patients. Correlation with intratumoral CAIX expression as well as clinicopathological factors and outcome was analyzed.Results: CAIX expression was observed in 81.9% of the tumor specimens; 62.0% showed a moderate or strong staining intensity. Moderate/strong expression was associated with squamous histology (p = 0.024), advanced tumor stage (p = 0.001), greater invasion depth (p = 0.025), undifferentiated tumor grade (p < 0.001) and high preoperative SCC-Ag values (p = 0.042). Furthermore patients with moderate/strong intratumoral CAIX expression had a higher number of metastatic lymph nodes compared to those with none/weak intratumoral expression levels (p = 0.047) and there was a non-significant association between high intratumoral CAIX expression and shorter survival (p = 0.118). Preoperative serum concentrations of CAIX ranged between 23 and 499 pg/mL and did not correlate with intratumoral expression or other clinicopathological variables.Conclusion: CAIX is associated with advanced tumor stages and lymph node metastases in cervical cancer, potentially representing a new target in this disease. In contrast to other epithelial cancers we could not observe a correlation between serum CAIX and its intratumoral expression. © 2011 Woelber et al; licensee BioMed Central Ltd. Source

Markowski D.N.,University of Bremen | Bartnitzke S.,University of Bremen | Loning T.,Albertinen Hospital | Drieschner N.,University of Bremen | And 3 more authors.
International Journal of Cancer | Year: 2012

Recurrent chromosomal alterations are found in roughly 20% of all uterine fibroids but in the majority cytogenetic changes are lacking. Recently, mutations of the gene mediator subcomplex 12 (MED12) have been detected in a majority of fibroids but no information is available whether or not they co-occur with cytogenetic subtypes as, e.g., rearrangements of the genes encoding high mobility group AT-hook (HMGA) proteins. In a total of 80 cytogenetically characterized fibroids from 50 patients, we were not only able to confirm the frequent occurrence of MED12 mutations but also to stratify two mutually exclusive pathways of leiomyomagenesis with either rearrangements of HMGA2 reflected by clonal chromosome abnormalities affecting 12q14∼15 or by mutations affecting exon 2 of MED12. On average the latter mutations were associated with a significantly smaller tumor size. However, G>A transitions of nucleotides c.130 or c.131 correlate with a significantly larger size of the fibroids compared to other MED12 mutations thus explaining the high prevalence of the former mutations among clinically detectable fibroids. Interestingly, fibroids with MED12 mutations expressed significantly higher levels of the gene encoding wingless-type MMTV integration site family, member 4 (WNT4). Based on these findings and data from the literature, we hypothesize that estrogen and the mutated MED12 cooperate in activating the Wnt pathway which in turn activates β-catenin known to cause leiomyoma-like lesions in a mouse model. The occurrence of a "fibroid-type mutation" in a rare histologic subtype of endometrial polyps suggests that this mechanism is not confined to uterine leiomyomas. Copyright © 2012 UICC. Source

Stang A.,Martin Luther University of Halle Wittenberg | Katalinic A.,University of Lubeck | Dieckmann K.-P.,Albertinen Hospital | Pritzkuleit R.,University of Lubeck | Stabenow R.,Common Cancer Registry of the Federal States of Berlin
Cancer Epidemiology | Year: 2010

Background: Currently, only 7 out of 16 Federal States of Germany provide testicular cancer incidence rates with an estimated completeness of at least 90% which complicates the regional comparison of incidence rates. The aim of this study was to provide a novel approach to estimate the testicular cancer incidence in Germany by using nationwide hospitalization data. Methods: We used the nationwide hospitalization data (DRG statistics) of the years 2005-2006 including 16,6 million hospitalizations among men. We identified incident testicular cancer cases by the combination of a diagnosis of testicular cancer and an orchiectomy during the same hospitalization and estimated the age-specific and age-standardized (World Standard Population) incidence of testicular cancer across Federal States. We also analyzed available cancer registry data from 2005 to 2006. Results: A total of 8544 hospitalizations indicated incident testicular cancer cases in 2005-2006. The nationwide crude incidence rate of testicular cancer was 10,6 per 100.000 person-years. The ratio of the number of registered cases (cancer registry) to the estimated number of cases based on the hospitalization statistics ranged between 79% and 100%. There was only little variation of the age-standardized DRG-based incidence estimates across Federal States (range: 8,2-10,6 per 100.000 person-years). Discussion: We provided testicular cancer incidence estimates for each of the 16 Federal States of Germany based on hospitalization data for the first time. The low within-population incidence variability in Germany and high between-population incidence variability in Europe may indicate that ecologic factors play a causal role in the European variation of testicular cancer. © 2009 Elsevier Ltd. All rights reserved. Source

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