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Itzehoe, Germany

Minner S.,Institute of Pathology | Kilgue A.,Institute of Pathology | Stahl P.,Institute of Pathology | Weikert S.,Charite - Medical University of Berlin | And 7 more authors.
Pathology | Year: 2010

Aims: Y chromosome losses have been described in 10-40% of bladder cancers and were suggested to be age-related. The clinical significance of chromosome Y losses is largely unknown, since only small sets of male bladder cancer patients have been evaluated in previous studies. The aim of this study was to further clarify the potential relevance of Y chromosome losses in bladder cancer with respect to clinical outcome and patient age. Methods: A pre-existing bladder cancer tissue microarray (TMA) with clinical follow-up data including 516 urothelial bladder cancers from male patients was utilised in this study. Y chromosome losses were analysed by multicolour fluorescence in situ hybridisation (FISH) using a centromere Y probe and a centromere X probe. p53 immunostaining data were available for all patients from a previous study. Results: Y chromosome losses were seen in 23% of 477 interpretable cancers from male patients. There was no significant difference in patient age in tumours with (67.4±4.3 years) or without (67.3±2.3 years) Y chromosome losses (p=0.9068). Y chromosome losses were equally frequent in tumours of all grades (p=0.7831) and stages (p=0.6140). There was also no association with p53 immunostaining (p=0.4092). Y chromosome losses were not associated with survival in 224 invasive urothelial cancers (pT2-4; p=0.2324), an increased risk for recurrences in 197 pTa tumours (p=0.7649) or increased progression risk in 76 pT1 tumours (p=0.4582). Conclusion: The data of this study show that Y chromosome losses are frequent in urothelial bladder cancer of all grades and stages, which could imply that loss of the Y chromosome is an early event in bladder cancer development. p53 mediated genomic instability is evidently not required for the development of Y chromosome losses. Since there was no correlation between Y chromosome losses and clinical outcome, detection of Y losses has no clinical relevance in urothelial bladder cancer. © 2010 Royal College of Pathologists of Australasia.


Lang D.S.,Research Center Borstel | Heilenkotter U.,Clinical Center Itzehoe | Schumm W.,Holsteinisches Breast Center Rendsburg | Behrens O.,Holsteinisches Breast Center | And 3 more authors.
Breast | Year: 2013

The determination of the invasion markers urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) has further improved the possibilities for individualized therapy of breast cancer. To date, quantitative measurement by ELISA, that needs large amounts of fresh, frozen material, is the only standardized procedure for diagnostic purposes. Therefore, the aim of this study was the establishment of a reliable alternative method based on immunohistochemistry (IHC) and image analysis requiring only small amounts of fixed tumor tissue. Protein expression of uPA and PAI-1 was analyzed in HOPE-fixed tumor samples using tissue microarrays (TMAs) and semiquantitative image analysis. The results of both methods were significantly correlated and risk assessment showed an overall concordance of 78% (83/107; high- and low-risk) and of 94% (74/79) regarding only high-risk patients. The data demonstrate that optimized IHC in combination with image analysis can provide adequate clinical significance compared to ELISA-derived determination of uPA and PAI-1. © 2013 Elsevier Ltd.


Lang D.S.,Research Center Borstel | Lang D.S.,Airway Research Center North | Marwitz S.,Research Center Borstel | Marwitz S.,Airway Research Center North | And 9 more authors.
Pathology and Oncology Research | Year: 2014

Metastasis represents a major problem in the treatment of patients with advanced primary breast cancer. Both Transforming Growth Factor-Beta (TGF-β) signaling and Plasminogen Activator (PA) components, urokinase-type Plasminogen Activator (uPA) and Plasminogen Activator Inhibitor-1 (PAI-1) represent a complex network crucial for such enhanced invasiveness of tumors and imply high prognostic/predictive and promising therapeutic potential. Therefore, protein expression of specific effector molecules comprising the main parts of the TGF-β signaling pathway were determined in HOPE-fixed human tumor tissues through IHC (Scoring) using tissue microarray (TMA) technique and correlated with respective uPA and PAI-1 levels determined earlier in the same TMAs through optimized IHC and semi-quantitative image analysis. TGF-β signaling was active in vast majority (96 %) of the tumor samples and 88 % of all cases were significantly correlated with established metastasis markers uPA and PAI-1. In addition, TGF-β was also closely associated with tumor size, nodal status and two steroid hormone receptors. Consistent interrelationships between TGF-β, PA components and additional tumor characteristics underline the superiority of such more comprising data with regards to confirming TGF-β signaling as a promising target system to inhibit metastasis in advanced breast cancer. © 2014 Arányi Lajos Foundation.


Minner S.,Institute of Pathology | Minner S.,University of Hamburg | De Silva C.,Institute of Pathology | Hoppner W.,University of Hamburg | And 6 more authors.
Pathology | Year: 2012

Aims: CD151 belongs to the group of tetraspanins and is aberrantly expressed in different tumours and differential expression has been associated with prognosis. The aim of this study was to clarify the relationship of CD151 expression with tumour phenotype and clinical outcome in bladder cancer. Methods: A bladder cancer tissue microarray containing samples from 686 urothelial bladder cancers was analysed by immunohistochemistry. Results: Membranous CD151 immunostaining was recorded in 409 (66.0%) of 620 analysable cases. High CD151 expression was seen in normal urothelium and in most non-invasive tumours. Low CD151 expression levels were associated with a more unfavourable tumour phenotype. CD151 staining was seen in 71.5% of 284 pTa, 62.1% of 145 pT1 and 60.4% of 187 pT2-4 cancers ( p=0.0033). CD151 staining was detectable in 77.3% of 75 grade 1, 71.1% of 273 grade 2 and 57.7% of 272 grade 3 cancers ( p<0.0001). CD151 expression status was not associated with overall or tumour-specific survival in muscle-invasive cancers (pT2-4), tumour progression in pT1 and recurrences in pTa tumours. Conclusion: On the basis of our data we conclude that loss of CD151 may contribute to bladder cancer progression through attenuation of cell adhesion. In clinically defined subgroups CD151 expression does not provide additional prognostic information. © 2012 Royal College of Pathologists of Australasia.


Kluth M.,University of Hamburg | Reynolds K.,University of Hamburg | Rink M.,University of Hamburg | Chun F.,University of Hamburg | And 9 more authors.
Cancer Genetics | Year: 2014

The MET protein is involved in the malignant progression of different tumors. This study aimed to analyze the relationship of MET expression with tumor phenotype and clinical outcome in bladder cancer and the role of gene amplification for MET overexpression. A bladder cancer tissue microarray containing 686 bladder cancers was analyzed by immunohistochemistry and by fluorescence in situ hybridization. MET immunostaining was seen in normal urothelium and was recorded in 459 of 560 analyzable urothelial carcinomas (82.0%). Low MET staining was associated with a more unfavorable tumor phenotype. MET staining was seen in 89.8% of 266 pTa, 81.1% of 132 pT1, and 69.4% of 160 pT2-4 cancers (P < 0.0001). MET staining was detectable in 92.4% of 66 grade 1, 85.6% of 257 grade 2, and 75.1% of 237 grade 3 cancers (P = 0.001). MET expression status was not associated with overall or tumor-specific survival in muscle-invasive cancers (pT2-4), tumor progression in pT1 cancers, or recurrences in pTa tumors. Only four of the analyzed tumors (0.8%) showed amplification of the MET gene. We conclude that MET is not overexpressed in urothelial cancer but rather downregulated in a fraction of cancers. Accordingly, rare amplification of the genomic area including the MET gene was not associated with MET protein overexpression. © 2014 Elsevier Inc.

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