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Wolfgang Hilbe

Publications and source records attributed to Wolfgang Hilbe.

8 recordsLinked to original sources
PubMed2006

Prognostic and diagnostic relevance of hnRNP A2/B1, hnRNP B1 and S100 A2 in non-small cell lung cancer.

BACKGROUND: S100 A2 and hnRNP A2/B1 (heterogeneous ribonucleoprotein A2/B1) with its splicing variant hnRNP B1 are proteins which are involved in cellular proliferation, differentiation and protein synthesis and are up-regulated in non-small cell lung cancer (NSCLC). Since previous studies using paraffin-embedded tissues indicated a high potential of these markers for diagnosis and screening the present analysis intended to validate these data applying cryostat sections. METHODS: 78 tumor-infiltrated lung cancer specimens and 66 adjacent histologically tumor-free tissues were analyzed; 11 autopsy specimens from patients who did not suffer from a malignant disease served as a control group. Cryostat sections were stained with monoclonal antibodies against hnRNP A2/B1, hnRNP B1 and S100 A2 and were compared with the previously established immunohistochemical profile of the same patients including EGFR, EGFRvIII, pEGFR, c-erbB-2, c-erbB-3, p53, Ki-67, bcl-2, p120 and microvessel density. Furthermore, these results were correlated with clinical parameters. RESULTS: Expression of hnRNP A2/B1, hnRNP B1 and S100 A2 was increased in the tumor group when compared with the microscopic tumor-free specimens in 10% versus 5% (n.s.), 91% versus 5% and 65% versus 6%, respectively. Increased S100 and A2 hnRNP A2/B1 expressions were negative prognostic factors. With the exception of an increased EGFR expression in hnRNP A2/B1 negative cases the three analyzed markers did not correlate with the immunohistochemical parameters tested previously. CONCLUSION: Comparison between tumor probes and tumor-free specimens of NSCLC patients failed to approve the diagnostic relevance of hnRNP A2/B1 shown in previous studies, whereas hnRNP B1 revealed a high tumor specificity that could be helpful for tumor cell screening. Moreover, S100 A2 and hnRNP A2/B1 confirmed to be valuable prognostic parameters.

Adult↗
PubMed2006

Targeted therapies in non-small cell lung cancer: proven concepts and unfulfilled promises.

Targeted therapies focus on signaling pathways in cancer cells and other molecular processes involved in oncogenesis. Recent approaches affect the following major groups: the epidermal growth factor receptor (EGFR)-family, angiogenesis, the eicosanoid pathway, the PKC/ Ras/ MAPK pathway, the proteasome and inducers of apoptosis. Numerous phase I and II trials have provided promising results and recently, anti-EGFR and anti-VEGF treatments have proven their efficacy in phase III trials. However, others failed in phase III settings (e.g. PKC- and matrix metalloproteinase inhibitors) and it is a moot point, whether patients have been selected properly. The huge amount of new medications raises questions like when to use which strategy in which sequence. The successful implementation of targeted agents into clinical routine will depend on the verification of sufficient predictive markers, allowing their economically reasonable usage. In the current review the up-to-date knowledge concerning targeted therapies in NSCLC is summarized and their therapeutical potential is discussed.

Angiogenesis Inhibitors↗
PubMed2006

High rate of molecular alteration in histologically tumour-free bronchial epithelium of NSCLC patients detected by multicolour fluorescence in situ hybridisation.

Detection of molecular abnormalities could provide an essential tool for the diagnosis of non-small cell lung cancer (NSCLC) and defining patients at risk for early relapse. Fluorescence in situ hybridisation (FISH) targeting 17 gene loci was applied to determine the frequency of molecular alteration in NSCLC probes and adjacent tumour-free bronchial epithelium. FISH was performed on fresh frozen specimens from 76 patients with histologically confirmed NSCLC and 54 specimens of adjacent tumour-free tissue. Routine autopsy lung tissue probes from 7 cancer-free patients served as a control group. Locus-specific (3p14.2, 3p21.2, 3p21.3, 3p25.3, 5p15.2, 7p12, 8q24.12, 9p21, 13q14, and 17p13.1) as well as centromere probes (4, 6, 7, 9, 11 and 16) were used. Molecular alterations using FISH on interphase nuclei were detected in 100% of NSCLC tumour specimens and 89% of microscopically tumour-free tissues of NSCLC patients. In histologically 'normal' epithelium, the most frequent alterations were seen with locus-specific probes for 3p14.2, 3p.21, 3p21.3, 3p25.3 and 7p12 and centromere-specific probes 11 and 16 (12-93%). As expected, the majority of genetic alterations seen in 'premalignant' specimens were found in the correlating tumour probes. None of the tested parameters revealed prognostic significance in univariate Cox analysis. FISH analysis, performing multicolour strategies, demonstrated its power in detecting genetic abnormalities in NSCLC specimens and even in tumour-free sections of tumour patients.

Adult↗
PubMed2004

Combination of cytology, fluorescence in situ hybridization for aneuploidy, and reverse-transcriptase polymerase chain reaction for human mammaglobin/mammaglobin B expression improves diagnosis of malignant effusions.

PURPOSE: The identification of malignant cells in effusions by conventional cytology is hampered by its limited sensitivity. The aim of this study was to improve tumor cell detection in effusions by molecular approaches. MATERIALS AND METHODS: A total of 157 effusions from patients with tumors and 72 effusions from patients without a history or evidence of malignancy were included in this study. All effusion specimens were evaluated in parallel by cytology, fluorescence in situ hybridization (FISH) for aneuploidy, and reverse-transcriptase polymerase chain reaction (RT-PCR) for expression of human mammaglobin (hMAM) and mammaglobin B (hMAM-B). RESULTS: In effusions from patients with tumors, the sensitivities of tumor cell detection by cytology, FISH, and hMAM and hMAM-B detection were 46.2%, 53.3%, 36.4%, and 57.7%, respectively. The corresponding specificities were 94.4%, 97.0%, 87.1%, and 88.6%. Notably, a high percentage of effusions containing malignant cells were in fact transudates, indicating the necessity for molecular diagnostic work-up of transudates collected from patients with tumors. Dependent on the tumor type, the use of appropriate marker combinations improved tumor cell detection in effusions significantly. By combining all four diagnostic tests, a positive test result indicating the presence of malignancy was achieved in 81.1%, with a fairly good specificity of 70.1%. CONCLUSION: Molecular techniques are definitely useful to detect malignancy in cytologically negative effusions. Tumor cell detection in effusions can be significantly improved by FISH and PCR techniques applying appropriate molecular markers. This finding should help to improve tumor staging, prognostic assessment, and treatment monitoring.

Aneuploidy↗
PubMed2003

Characterisation and predictive value of epidermal growth factor receptor status using quantitative real-time PCR combined with immunohistochemistry on non-small cell lung cancer specimens.

The frequency of increased EGFR-mRNA expression was determined in 57 patients suffering from NSCLC by applying quantitative real-time PCR. The findings were correlated with clinical parameters and the immunohistochemical (IHC) markers EGFR, c-erbB-2, c-erbB-3, Ki-67 and p53 on cryostat sections. Of the patients 46% showed increased EGFR-mRNA, 35% revealed an increased IHC-EGFR expression; 16% of the patients showed a combined positivity and 35% a combined negativity when applying both methods, and 17 (30%) of the cases revealed increased EGFR-mRNA without IHC-EGFR expression. This subgroup was characterised by p53 coexpression and the highest frequency of deaths (35% vs. 20%) indicating a more aggressive tumour type. In contrast to IHC - where positivity was seen predominantly in squamous cell carcinomas (48% vs. 27%) - EGFR-mRNA expression was observed equally in both histological subtypes (48% vs. 43%). PCR-EGFR and IHC-EGFR tumour typing identifies different tumour characteristics with different clinical courses. Whether this combined typing could help to identify patients who respond to anti-EGFR therapies is worth further testing.

Carcinoma, Non-Small-Cell Lung↗
PubMed2003

Automated real-time PCR to determine K-ras codon 12 mutations in non-small cell lung cancer: comparison with immunohistochemistry and clinico-pathological features.

A real-time PCR technique with automated computerized analysis (TaqMan ) was tested to detect K-ras mutations in 66 patients suffering from NSCLC. This technology is characterized by high reproducibility of data and a time-saving analysis procedure. In 11% (7/66) of the tumour specimens and 2% (1/58) of adjacent tumour-free lung specimens a K-ras codon 12 mutation was detected. In adenocarcinomas containing > or =40% tumour cells, however, K-ras mutations were seen in 25% of the cases. The point mutations detected in tumours were GGT right curved arrow TGT in five cases and GGT right curved arrow GTT in two cases. As compared with immunohistochemical parameters, the K-ras mutated group was characterized by a c-erbB-2 negativity (p=0.04) and a smaller number of c-erbB-3 (p=0.02) positive cases. EGFR, bcl-2, p53, Ki-67 and p120 expression did not differ significantly. Determination of the K-ras point mutations by automated TaqMan PCR in NSCLC tumour specimens is feasable and highly specific. Due to its high throughput capacity this method represents a valuable tool for routine screening.

Carcinoma, Non-Small-Cell Lung↗
PubMedDate not supplied

Comparison of automated cellular imaging system and manual microscopy for immunohistochemically stained cryostat sections of lung cancer specimens applying p53, ki-67 and p120.

Seventy-one frozen lung tissue specimens from 52 patients suffering from non-small cell lung cancer (NSCLC) were analysed in this study. Cryostat sections were stained with monoclonal antibodies against p53, ki-67 and p120, all of which are of prognostic value in NSCLC. Slides were evaluated by standard manual microscopy (MM) and using a new Automated Cellular Imaging System (ACIS). The results obtained with ACIS correlated significantly with MM examination (p<0.001). However, ACIS showed a higher sensitivity, especially for specimens with a low infiltration volume. In 15 (6.8%) MM negative cases singular positive cells were identified with ACIS. In cases with a high infiltration volume subjective (MM) quantitation tended to overestimate the number of infiltrating cells. ACIS guaranteed a high reproducibility of data. We conclude that ACIS-assisted analysis is a valid means of investigating the p53, ki-67 and p120 antibody expression in cryostat sections of lung cancer specimens. ACIS can complement conventional manual microscopy due to its higher accuracy, sensitivity and better reproducibility of data.

Adenocarcinoma↗