Biomedical subjects

K Schlüns

Publications and source records attributed to K Schlüns.

11 recordsLinked to original sources

PubMed2003

CD24 is an independent prognostic marker of survival in nonsmall cell lung cancer patients.

Originally identified as a B-cell marker, expression of the cell surface molecule CD24 has meanwhile been observed in a variety of human malignancies. It appears to function as a ligand of P-Selectin, an adhesion molecule that is present in activated platelets and endothelial cells. We aimed to determine the rate of CD24 expression in our nonsmall cell lung cancer (NSCLC) collection and to clarify its correlation with clinicopathological parameters including patients' survival. A total of 89 NSCLC were analysed immunohistochemically using a monoclonal CD24 antibody (clone 24C02) and a standard detection system (LSAB, DAKO) on NSCLC tissue microarrays (TMA). The staining was semiquantitatively scored (0, 1+, 2+, 3+) and grouped into high (2+, 3+)- and low (0, 1+)-level expression for statistical analysis. A high level of CD24 expression was observed in 45% of the cases, preferentially adenocarcinomas. Patients whose tumours had a high CD24 expression showed a significantly shorter median survival time of 23 months vs 38 months (P=0.033, log-rank test). Similarly tumour, grading, nodal status and clinical stage were significant prognostic markers in univariate survival analysis. Importantly, in the Cox regression-based multivariate analysis, CD24 expression (P=0.025) together with tumour stage (P=0.006) and grade (P=0.011) proved to be independent prognostic parameters. We hypothesise that the decreased survival of NSCLC patients with strongly CD24-positive tumours is related to an enhanced propensity of haematogenous metastasis formation, which might be P-Selectin mediated.

Adult↗

PubMed2003

Gene expression profiles in human non-small and small-cell lung cancers.

Suppression subtractive hybridisation (SSH) was performed comparing normal bronchial epithelial cells with a lung squamous cell carcinoma (SCC) and a metastatic small-cell lung carcinoma (SCLC). The sequence analysis of four cDNA libraries revealed 869 individual sequences. Of these, 342 were tested using northern blots of lung cancer cell lines representing the three major subtypes (SCC, adenocarcinoma, SCLC) which confirmed the differential expression of 236 cDNAs. The extended analysis of 31 randomly chosen fragments confirmed the validity of the approach to identify genes associated with lung cancer development. Additionally, five novel full-length cDNA were isolated encoding the microtubule-associated proteins 1A/1B light chain 3, the epithelial V-like antigen 1 (EVA1), the GTP-binding protein SAR1, a new member of the S100-type calcium binding protein family and a new homeobox-containing gene.

Blotting, Northern↗

PubMed2003

Genetic imbalances with impact on survival in colorectal cancer patients.

AIMS: To investigate the prognostic significance of chromosomal alterations in colorectal cancer patients. Histopathological tumour classification is still considered to be the gold standard for the characterization of solid tumours. However, it is well known that such established parameters do not satisfactorily predict the clinical outcome in individual cases. Markers that reliably predict survival are needed. These markers should guide the clinical treatment of neoplastic disease. METHODS AND RESULTS: Chromosomal imbalances in 61 colorectal carcinoma specimens in 37 patients determined by comparative genomic hybridization were correlated with patient survival using custom-made computer software which enabled the assessment of individual chromosomal loci. Kaplan-Meier analysis revealed that over-representations of 2p14-15, 6q23-6q24, 15q22-15q23, 22q11.2 and deletions of 1p36.1-36.2, 4q31.3, 4q35, 8q12-q21, 8p11.2 and 9p22 were significantly associated with shorter disease-specific survival, whereas over-expression of 20q13.3 and deletion of 18q11.2 were significantly associated with longer disease-specific survival in this collection of colorectal cancers. Multivariate Cox proportional hazards regression models consistently identified gains of 2p14-15, 15q22-23, 22q11.2 and losses of 1p36.1-36.2 and 4q35 as independent markers of shorter patient survival carrying greater significance than the classical clinicopathological parameters of nodal status and tumour grade. CONCLUSIONS: These five markers allow a molecular categorization of patients into high and low clinical risk groups. Thus, the genomic data have refined the histopathological classification highlighting the necessity for a supplementary genetically based stratification of colorectal cancer.

Adenocarcinoma↗

PubMed2001

Overexpression of c-erbB2 protein correlates with disease-stage and chromosomal gain at the c-erbB2 locus in non-small cell lung cancer.

Overexpression of the c-erbB2 protein is observed in a variety of malignancies including non-small cell lung cancer (NSCLC). We aimed to determine the rate of c-erbB2-overexpression in our tumour collection and to clarify its correlation with the chromosomal status at the c-erbB2 locus 17q21 in NSCLC. Eighty-nine NSCLC were analysed immunohistochemically using a polyclonal c-erbB2 antibody (DAKO). The staining was scored according to the guidelines of the Clinical Trial Assay recommendations (0-3+). Of these, 44 cases were also analysed by comparative genomic hybridisation (CGH). Overexpression was observed in 37% of the cases (score>1) which was associated with higher disease stages and a positive nodal status in adenocarcinomas. Chromosomal gains at 17q21 were clearly correlated with overexpression of the gene (P=0.009). In addition, there was a highly significant correlation between the c-erbB2 expression comparing the whole section immunostaining analysis and a 127 lung tumour tissue array which included 74 of the 89 cases that were analysed by the classical procedure. We conclude that c-erbB2 is a marker of tumour progression in NSCLC which can be observed on protein level and reflects chromosomal alterations at 17q21.

Adult↗

PubMed2000

Patterns of chromosomal imbalances in invasive breast cancer.

Invasive breast carcinomas are characterized by a complex pattern of chromosomal alterations. We applied comparative genomic hybridization (CGH) to analyze 105 primary breast carcinomas using histograms to indicate the incidence of DNA imbalances of tumor subgroups and difference histograms to compare invasive ductal carcinomas (IDC) with lobular carcinomas (ILC), well and poorly differentiated carcinomas (G1/G3) and estrogen receptor-positive and -negative tumors (ER(+)/ER(-)). Only single imbalances showed a higher incidence in ILC compared with IDC, i.e., gains on chromosomes 4 and 5q13-q23 as well as deletions on chromosomes 6q, 11q14-qter, 12p12-pter, 16q, 17p, 18q, 19, and 22q. Of these, particularly gains of 4 and losses at 16q21-q23, and 18q12-q21 were statistically significant. For most loci, IDC showed more alterations providing a genetic correlate to the fact that ductal carcinoma overall is associated with a worse prognosis than ILC. Of these, many imbalances showing statistical significance were also observed in G3 and ER(-) tumors, i.e., deletions at 2q35-q37, 3p12-p14, 4p15-p16, 5q, 7p15, 8p22-p23, 10q, 11p, 14q21-q31, 15q, and gains at 2p, 3q21-qter, 6p, 8q21-qter, 10p, 18p11-q11, and 20q, suggesting that they contribute to a more aggressive tumor phenotype. By contrast, gains on chromosome 5q13-q23 as well as deletions at 6q, 16q and 22q were more prevalent in G1 and ER(+) tumors. The ratio profiles of all cases as well as histograms are accessible at our CGH online tumor database at http://amba.charite.de/cgh. Our results highlight distinct chromosomal subregions for cancer-associated genes. In addition, these imbalances may serve as markers for a genetic classification of invasive breast cancer.

Adult↗

PubMed2000

Gene expression profiling of advanced lung cancer.

Lung cancer is a highly aggressive neoplasm with 85% mortality. To identify new tumor-associated genes, we compared the expression profile of a primary metastasizing adenocarcinoma with normal airway epithelial cells. Two cDNA libraries of up- and downregulated genes were generated, comprising 253 and 299 clones, respectively. The sequence analysis revealed 205 different known genes and 314 cDNA fragments of unknown functions. Northern-blot analysis of 167 clones confirmed differential expression in 58%, and indicated a similar expression pattern in additional lung-cancer cell lines for selected clones, strengthening the value of this model for the identification of new candidate genes in lung carcinogenesis.

Chromosome Mapping↗

PubMed2000

Telepathology by the Internet.

A new concept for telemicroscopy has recently been introduced using the Internet and conventional web browser, with Java support for microscope remote control as well as image transfer and discussion (http://amba.charite.de/telemic/). The system has two major components: the telemicroscopy server, which is a computer with Internet access connected to the automatic microscope, and the telemicroscopy client, who remotely operates the microscope. This simplified telemicroscopy system allows any Internet user to become a consultant for telepathology without the acquisition of specialized hardware or software. For the inquirer seeking advice, however, this solution is still very expensive, since it requires a fully automated microscope. The present study describes a system that can be used for conventional microscopes. A video camera mounted on a microscope with a photo tube is connected to the frame grabber of a PC. Java-based telemicroscopy software transforms the computer into an Internet server, which automatically distributes new microscope images, after manual operations, to all connected clients. Any Internet user can access the web page of the server to become a telemicroscopy client. A Chat function allows for the online exchange of written text and a Discuss function enables the mouse button to display an arrow to all connected clients, which highlights distinct structures of the images. The system was optimized for simplicity, while presenting all features that are necessary to show and discuss difficult cases with any expert in the field who has Internet access. It offers new perspectives for telepathology and it is envisaged that many pathologists and scientists will use this facility to connect their personal microscopes to the Internet, forming a network for teleconsultation. To foster this development, the software described in this paper is being made freely available. Hopefully, this development will promote communication between pathologists and may thus increase the quality of diagnosis. Information on inquiry and installation of the software is available at the website mentioned above. Telemicroscopy sessions using the Telemic version for conventional microscopes can be scheduled by contacting the authors by e-mail (iver. petersen@charite.de).

Communication↗

PubMed2000

Genetic imbalances with impact on survival in head and neck cancer patients.

Chromosomal imbalances in 113 primary head and neck squamous cell carcinomas (HNSCCs) determined by comparative genomic hybridization were correlated with patients survival using custom-made computer software which enabled the assessment of individual chromosomal loci. The Kaplan-Meier analysis revealed that overrepresentations of 2q12, 3q21-29, 6p21.1, 11q13, 14q23, 14q24, 14q31, 14q32, 15q24, 16q22, and deletions of 8p21-22 and 18q11.2 were significantly associated with both shorter disease-free interval and disease-specific survival in this tumor collective. Multivariate Cox proportional hazards regression models consistently identified the gains of 3q21-29, 11q13, and the loss of 8p21-22 as independent prognostic markers carrying a higher significance than the nodal status as the only clinicopathological parameter with statistical importance. In addition, these three markers allowed a molecular dissection of the patients with low clinical risk (pN0 and pT2 tumors). Thus, the genomic data being derived from the evaluation of primary HNSCC enabled a stratification of the patients into subgroups with different survival highlighting the necessity of a genetically based tumor classification for refining diagnosis and treatment of HNSCC patients.

Chromosome Aberrations↗

PubMed2000

Human papilloma virus status and chromosomal imbalances in primary cervical carcinomas and tumour cell lines.

Human papilloma virus (HPV) infection is the crucial step in the initiation of cervical carcinomas. In addition, HPV18 has been implicated in tumour progression and adverse clinical outcome. We determined the HPV types in 12 primary cervical carcinomas and 12 cell lines and compared the findings with the comparative genetic hybridisation (CGH) pattern of chromosomal alterations. The most frequent alteration was the deletion at 3p14 followed by the loss of 2q34-q36 along with 3q gain. High risk HPV types were detected in all samples except one primary tumour. In contrast to the normal distribution, HPV18 was present in 75% of cases including all cell lines. The cell lines carried a higher number of genetic alterations and a different CGH pattern for several chromosomes than the primary tumours, despite microdissection. Purely HPV18 positive cases indicated a high incidence of imbalances at specific loci with peaks of the histogram coinciding with known HPV integration sites. The study suggests that HPV infection is associated with a recurrent pattern of chromosomal changes in cervical carcinomas and that the development and progression of these alterations is triggered by integration into the host genome.

Carcinoma, Squamous Cell↗

PubMed2000

Chromosomal alterations in the clonal evolution to the metastatic stage of squamous cell carcinomas of the lung.

Comparative genomic hybridization (CGH) was applied to squamous cell carcinomas (SCC) of the lung to define chromosomal imbalances that are associated with the metastatic phenotype. In total, 64 lung SCC from 50 patients were investigated, 25 each with or without evidence of metastasis formation. The chromosomal imbalances summarized by a CGH histogram of the 50 cases revealed deletions most frequently on chromosomes 1p21-p31, 2q34-q36, 3p, 4p, 4q, 5q, 6q14-q24, 8p, 9p, 10q, 11p12-p14, 13q13-qter, 18q12-qter and 21q21. DNA over-representations were most pronounced for chromosomes 1q11-q25, 1q32-q41, 3q, 5p, 8q22-qter, 11q13, 12p, 17q21-q22, 17q24-q25, 19, 20q and 22q. In ten cases, paired samples of primaries and at least one metastasis were analysed. The comparison revealed a considerable chromosomal instability and genetic heterogeneity; however, the CGH pattern indicated a clonal relationship in each case. The difference in histograms from the metastatic and non-metastatic tumour groups was most useful in pinpointing chromosomal imbalances associated with the metastatic phenotype, indicating that the deletions at 3p12-p14, 3p21, 4p15-p16, 6q24-qter, 8p22-p23, 10q21-qter and 21q22, as well as the over-representations at 1q21-q25, 8q, 9q34, 14q12 and 15q12-q15, occurred significantly more often in the metastatic tumour group. The comparison of the paired samples confirmed these findings in individual cases and suggested distinct genetic changes, in particular the extension of small interstitial deletions, during tumour progression. Importantly, metastasis-associated lesions were frequently detectable in the primary tumour providing a method of identifying patients at risk for tumour dissemination. Individual profiles and histograms are accessible at our web site http://amba.charite.de/cgh.

Carcinoma, Squamous Cell↗

PubMed2000

Chromosomal imbalances in brain metastases of solid tumors.

Metastases account for approximately 50% of the malignant tumors in the brain. In order to identify structural alterations that are associated with tumor dissemination into the central nervous system we used Comparative Genomic Hybridization (CGH) to investigate 42 brain metastases and 3 primary tumors of 40 patients. The metastases originated from lung cancer (14 cases), melanomas (7), carcinomas of breast (5), colon (5), kidney (5), adrenal gland (1) and thyroid (1). In addition, tumors of initially unknown primaries were assessed in 3 cases. The highest incidence of DNA gains were observed for the chromosomal regions 1q23, 8q24, 17q24-q25, 20q13 (>80% of cases) followed by the gain on 7p12 (77%). DNA losses were slightly less frequent with 4q22, 4q26, 5q21, 9p21 being affected in at least 70% of the cases followed by deletions at 17p12, 4q32q34, 10q21, 10q23-q24 and 18q21-q22 in 67.5% of cases. Two unusual narrow regional peaks were observed for the gain on 17q24-q25 and loss on 17p12. The incidence at individual loci can be viewed at our CGH online tumor database at http:// amba.charite.de/cgh/. The metastases of each tumor type showed a recurrent pattern of changes. In those cases with primary tumor and metastases available, the CGH pattern exhibited a high degree of conformity. In conclusion, our data suggests that specific genetic lesions are associated with tumor dissemination into the nervous system and that CGH analysis may be a useful supplementary tool for classification of metastases with unknown origin.

Brain Neoplasms↗