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Article: Mismatch repair proteins hMLH1 and hMSH2 are differently expressed in the three main subtypes of sporadic renal cell carcinoma.
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ABSTRACT: We studied the role of minor mismatch repair proteins (MMR) human MutL homologue 1 (hMLH1) and human MutS homologue 2 (hMSH2) in the main subtypes of renal cell carcinoma (RCC). Expression of MMR proteins hMLH1 and hMSH2 were investigated in 166 RCC tumors, containing the main subtypes by immunohistochemistry. Furthermore, each tumor was screened for microsatellite instability (MSI) using the National Cancer Institute consensus panel for hereditary non-polyposis colon carcinoma as well as for elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) by 10 additional markers. MSI was found only in 2.0% of analyzable cases and EMAST was detected only in 1 patient. hMLH1 and hMSH2 expression was reduced in 83.7 (118/141) and 51.2% (65/127) of cases, respectively, in a subtype-specific manner. None of the clear cell RCC tumors retained a high hMLH1 expression and 92.0% lost hMLH1 completely, while papillary and chromophobe RCC preserved the expression in 25.0 and 33.3% of cases (p < 0.001). Subtype specificity was also present in hMSH2 staining, where chromophobe RCC retained a high expression in 41.7% of cases, while clear cell and papillary tumors did not (29.9 and 23.1%; p = 0.01). MSI and EMAST are rare events in sporadic RCC, whereas diminished MMR protein expression is linked to tumor entity and might contribute to the different biological behavior of the RCC subtypes.Pathobiology 02/2012; 79(3):162-8. · 1.18 Impact Factor -
Article: NAD(P)H:Quinone Oxidoreductase 1 (NQO1) P187S Polymorphism and Prostate Cancer Risk in Caucasians.
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ABSTRACT: NAD(P)H:quinone oxidoreductase 1 (NQO1) catalyses the reduction of quinoid compounds to hydroquinones, preventing the generation of free radicals and reactive oxygen. A "C" to "T" transversion at position 609 of NQO1, leading to a nonsynonymous amino acid change (Pro187Ser, P187S), results in an altered enzyme activity. No NQO1 protein activity was detected in NQO1(609)TT genotype, and low to intermediate activity was detected in NQO1(609)CT genotype compared with (609)CC genotype. Thus, this polymorphism may result in altered cancer predisposition. For prostate cancer, only sparse data are available. We therefore analyzed the distribution of the NQO1 P187S SNP (single nucleotide polymorphism) in prostate cancer patients and a healthy control group. Allelic variants were determined using RFLP analysis. Overall, 232 patients without any malignancy and 119 consecutive prostate cancer patients were investigated. The genotype distribution in our cohorts followed the Hardy-Weinberg equilibrium in cases and controls. The distribution of the NQO1 codon 187 SNP did not differ significantly between prostate cancer patients and the control group (p = 0.242). There was also no association between the allelic variants and stage or Gleason score of the tumors. The NQO1 P187S SNP was not significantly associated with an increased prostate cancer risk in our cohorts. The SNP has also no influence on histopathological characteristics of the tumors. A combined analysis of all available data from published European studies also showed no significant differences in the genotype distribution between controls and prostate cancer patients. Our data suggest a minor role of the NQO1 nucleotide 609 polymorphism in prostate carcinogenesis.International Journal of Molecular Sciences 01/2012; 13(9):10959-69. · 2.60 Impact Factor -
Article: Substaging by estimating the size of invasive tumour can improve risk stratification in pT1 urothelial bladder cancer-evaluation of a large hospital-based single-centre series.
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ABSTRACT: The outcome of patients with pT1 bladder cancer cannot yet be reliably estimated. The aim of this study was to evaluate several parameters in one of the largest series of initial pT1 bladder cancers. Specimens of 309 patients with pT1 urothelial carcinoma were re-evaluated histologically, including size of infiltrating tumour area estimated as equal to or smaller than one high-power field (HPF) or larger than one HPF, and tumour infiltration in relation to the muscularis mucosae (pT1a/b). Results were correlated with clinical follow-up. Substaging by HPF was associated with tumour recurrence, progression and survival in univariate analysis, and with recurrence and progression in multivariate analysis. According to the World Health Organization (WHO) 1973 grading, 220 tumours were G3, 89 were G2, and none was G1. Tumour grading was an independent prognostic marker of survival. Substaging by HPF revealed G2 and G3 tumours as distinct prognostic groups with regard to recurrence and progression. No significance was found for substaging pT1a/pT1b. An infiltrative growth pattern was significantly correlated with progression and survival in univariate analysis. Comparison of two systems of substaging pT1 bladder cancer shows that measurement of the size of infiltrating tumour area by HPFs may improve risk stratification. An infiltrative growth pattern on the invasion front should be documented in the pathological report, indicating a worse outcome. Additional studies are needed to find further parameters detecting high-risk tumours.Histopathology 10/2011; 59(4):722-32. · 3.08 Impact Factor -
Article: Patients with localised prostate cancer (t1 - t2) show improved overall long-term survival compared to the normal population.
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ABSTRACT: Background: Little information is available on the long-term outcomes of patients with localised prostate cancer.Objective: To examine the long-term survival of patients with localised prostate gland carcinoma T1 - T2, N0, M0 (UICC stage I and II) compared to the normal population.Design: Retrospective cohort.Setting: Regensburg, Germany.Participants: Data on 2121 patients with histologically-confirmed, localised prostate cancer diagnosed between 1998 and 2007 were extracted from the cancer registry of the tumour centre in Regensburg, Germany.Measurements: Overall survival rate in the patient cohort was estimated and compared to the expected survival rate of a comparable group in the general population derived from the official life-tables of Germany stratified by age, sex and calendar year.Results: Ten years after diagnosis, patients with stage I and II localised prostate gland carcinoma had an approximately 10% increase in survival compared to the normal male population (Relative Survival = 110.7%, 95%-CI 106.6 - 114.8%).Limitations: We did not examine the effect of cancer treatment or cancer aggressiveness on the overall survival of patients. We did not assess the incidence of subsequent non-primary cancers in our patient population or how this incidence affects the patients' follow-up care and survival.Conclusions: Patients with stage I+II localised prostate gland carcinoma have improved survival compared with the normal male population. This finding cannot be explained solely by the administration of prostate carcinoma treatments, suggesting that men who participate in PSA screening may have better overall health behaviors and care than men who do not participate in screening. Future research should examine how treatment choice, especially an "active surveillance" approach to care, affects survival in these patients more than ten years after diagnosis.Journal of Cancer. 01/2011; 2:76-80. -
Article: P53 codon 72 (Arg72Pro) polymorphism and prostate cancer risk: association between disease onset and proline genotype.
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ABSTRACT: The tumor suppressor gene p53 plays an important role in the stress response of the cell and is mutated in 50% of all human tumors. The p53 Arg72Pro single-nucleotide polymorphism (SNP) was found to be associated with an increased risk of various malignancies. Biochemical and biological differences between the 2 polymorphic variants of wild-type P53 might lead to distinct susceptibility to HPV- and non-HPV-induced tumors. For prostate cancer, only limited data are available, especially in the Caucasian population. Therefore, we determined the distribution of the Arg72Pro SNP in a Caucasian case-control study including 118 prostate cancer patients and 194 male controls without any malignancy using restriction fragment length polymorphism analysis. A subset of 33 tumors was tested for HPV infection, and no HPV DNA was found. Cases and controls showed similar distributions of alleles in the SNP (p = 0.720). Regarding the onset of the disease, patients diagnosed at ≤60 years of age and older patients (>60 years of age) showed a significant difference in genotype distribution (p = 0.035); there was also an increased occurrence of risk allele Pro72 in cases aged ≤60 years (p = 0.045). A subset of 64 prostate tumors was stained immunohistochemically for P53. 5 of 64 prostate tumors (7.8%) were positive for P53 expression, indicating integrity of the protein in the majority of cases. Genotype distribution showed no association with the Gleason score or additional histopathological characteristics. This study shows that the overall risk of prostate cancer was not associated with Arg72Pro SNP and HPV infection in our cohort. However, disease onset might be modulated by the p53 Pro72 allele, suggesting an important role of apoptosis regulation in prostate carcinogenesis.Pathobiology 01/2011; 78(4):193-200. · 1.18 Impact Factor
