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Biomedical subjects

M Poetsch

Publications and source records attributed to M Poetsch.

At least 19 recordsLinked to original sources
PubMed2005

Expression of Skp2 and p27KIP1 in naevi and malignant melanoma of the skin and its relation to clinical outcome.

Skp2 (S-phase kinase associated protein 2) controls progression from G- to S-phase by promoting the proteolysis of the cyclin dependent kinase inhibitor p27KIP1. Despite the fact that a p27KIP1 decrease has been documented in melanoma progression, the role of Skp2 in these tumours is unknown. We therefore examined by immunohistochemistry the expression of Skp2, p27KIP1 and Ki-67 in 10 naevi (Ns), 15 superficial spreading melanomas (SSMs), 10 nodular melanomas (NMs) and 14 melanoma metastases (Ms). Nuclear Skp2 expression augmented with increasing malignancy (Ns: 1.4%, SSMs: 5.6%, NMs: 17.3%, Ms: 19.1%). In all tumours nuclear Skp2 expression correlated with Ki-67 (p=0.024) and inversely with p27KIP1 (p=0.007). A cytoplasmic reaction for Skp2 was also observed in most tumours and its expression decreased from Ns (12.3%) to SSMs (7.9%) and NMs (4.5%). In contrast, Ms showed an increase of cytoplasmic Skp2 (11.9%) that correlated with its nuclear expression (p=0.016). While nuclear Skp2 expression correlated with the pT-level (p=0.023), Clark-level (p=0.023) and Breslow index (p=0.019), the cytoplasmic Skp2 expression might be of biological significance only in NMs since it correlated with tumour depth (p=0.02) and pT-level (p=0.025). Our data suggests that Skp2 could contribute to melanoma progression. This is further highlighted by the fact that vertical growth phase (VGP) melanomas show significant higher nuclear Skp2 expressions when compared with the harmless radial growth phase (RGP) (p=0.047). Also nuclear Skp2 expression correlates with a reduced survival time (p=0.025) in melanoma.

Carrier Proteins↗
PubMed2003

Can different genetic changes characterize histogenetic subtypes and biologic behavior in sporadic malignant melanoma of the skin?

In sporadic malignant melanoma, different chromosomal regions with nonrandom aberrations have been discovered, including 1p36, 6q, 9p and 10q. First results provide a genetic basis for the concept of primarily vertical, biologically aggressive melanomas and radial growing, mostly benign melanomas. These are mainly represented by nodular melanoma (NM) and early superficial spreading melanoma (SSM), respectively. Deletions in 1p36 could be found only in NMs and metastatic melanoma. Aberrations of chromosome 10 occur predominantly in NMs, whereas deletions on chromosome 9 are more frequent in SSMs. Despite a variety of genes tested, neither a tumor suppressor gene with importance in all malignant melanomas of the skin nor one clearly defining the transition from the radial growth phase to the vertical growth phase has been determined. Nevertheless, the pattern of genetic alterations may soon lead to finding such genes and development of drugs targeting these genes or their products, which would be of great benefit to melanoma patients.

Animals↗
PubMed2003

Lhermitte-Duclos disease in 3 children: a clinical long-term observation.

We report three boys in whom a diagnosis of Lhermitte-Duclos disease (LDD) was assumed from characteristic neuroimaging findings. LDD was confirmed by an open biopsy in patient 1, while a biopsy in patient 2 was inconclusive. Histologic confirmation in patient 3 was deliberately not attempted. However, a follow-up observation of stable clinical and neuroimaging findings over 2, 5 and 11 years, respectively, support the diagnosis of LDD. Despite extensive expansion of the lesion with brainstem involvement, clinical signs in two boys were minimal, while one patient has cognitive impairment and a complex oculomotor disturbance. So far we found no evidence for an association with Cowden disease (CD). No germline PTEN mutations were detected in these children, but the amount of available biopsy tissue in patients 1 and 2 was insufficient for a complete genetic analysis of tumor tissue. In conclusion, LDD can usually be diagnosed by MRI. In view of the favourable natural history, a conservative "wait and see" strategy is justified, particularly if radical tumor resection is not possible. LDD is often not associated with CD and germline PTEN mutations seem not to be present in isolated LDD.

Cerebellar Neoplasms↗
PubMed2002

Clear cell chondrosarcoma of the larynx: a case report of a rare histologic variant in an uncommon localization.

The authors describe a clear cell chondrosarcoma of the larynx. The clear cell type is a rare variant of chondrosarcoma that only twice has been reported in this localization. The light-microscopic diagnosis of the actual case was confirmed by immunohistochemical results, in particular by positive staining for S-100 protein and collagen type II, and ultrastructural findings. Loss of heterozygosity analysis demonstrated allelic loss at 9p22 and 18q21, but neither in the region of the Rb gene on chromosome 13q nor at the p53 locus on chromosome 17p where allelic loss has already been reported in chondrosarcomas. Furthermore, our molecular genetic investigations revealed a methylation of the cell cycle control gene p16, which is localized on chromosome 9p. This characteristic has been recorded previously only in high-grade chondrosarcomas. Mutations in the exons of p16, alterations of the putative tumor suppressor gene MMAC1/PTEN on chromosome 10q, or an amplification of the cyclin D1 gene (CCND1) on 11q13, which were found to be changed in other studies of chondrosarcomas, could not be demonstrated here.

Chondrosarcoma↗
PubMed2001

Analysis of microsatellite polymorphism in red deer, roe deer, and fallow deer -- possible employment in forensic applications.

DNA microsatellites play a major role in population genetics, linkage mapping, and parentage studies of mammals. In addition, they may be used for forensic purposes, if an individual identification of a specific animal is necessary. Therefore, we tested a variety of microsatellite polymorphism derived from reindeer (Rangifer tarandus) by PCR and sequencing analysis for use in red deer (Cervus elaphus), roe deer (Capreolus capreolus) and fallow deer (Dama dama). Twelve of these microsatellites were selected for further analysis. In all these microsatellite polymorphism short tandem repeats could be detected for one or all three species as shown by sequencing analysis. In red deer, more than two alleles were found in eight microsatellites, in roe deer more than two alleles could be demonstrated in seven microsatellites, whereas in fallow deer more than two alleles were found in only two microsatellite polymorphism. A comparison of sequences of PCR products from the three deer species with the sequences of reindeer revealed several differences between the four species. In six microsatellites -- selected because or their reliability in PCR and because of their polymorphic character -- we established a sequenced allelic ladder and give population data of all three species from 82 deer of the Northeast region of Germany (Vorpommern). Our results show the possibility to use microsatellite polymorphism in the identification of deer in forensic applications like poaching.

Alleles↗
PubMed2001

Multiple chromosomal underrepresentations detected by interphase cytogenetics - possible prognostic markers in head and neck tumors?

Relevant prognostic factors for head and neck squamous cell carcinoma are tumor extension (pT), occurrence of lymph node metastases (pN) and grade of differentiation (G). We tried to correlate these histological characteristics with numerical aberrations of whole chromosomes as demonstrated by fluorescence in situ hybridization techniques (FISH). Therefore, we investigated isolated interphase cells from paraffin sections of squamous cell carcinomas of the head and neck region from 46 patients with centromeric DNA probes for chromosomes 1, 3, 4, 6, 7, 9, 10, 11, 12, 15, 17, 18, X and Y. The majority of tumor samples showed aneuploidy for most chromosomes analyzed. The main chromosomal abnormality was loss of chromosomal material, predominantly of chromosomes 3 (28%), 6 (20%), 9 (26%), 10 (24%) and 18 (33%). Multiple deletions could be demonstrated more frequently in poorly differentiated carcinomas (88% G3-tumors with more than one deletion in contrast to 66% G2-tumors). The occurrence of multiple deletions may also correlate with progression in lymph node metastasis (66% in pN0-tumors vs. 85% in pN2-tumors), whereas the differences between the stages of primary tumor extension were not so obvious. Despite of a some-what disproportionate distribution of tumors in the different pT- and pN-stages and the rather low number of cases, our results suggest a relationship between the quantity of chromosomal underrepresentation, grade of differentiation and higher lymph node stage. Therefore, they underline the importance of chromosomal deletions as a possible additional prognostic marker in head and neck squamous cell carcinoma.

Aneuploidy↗
PubMed2001

PTEN/MMAC1 in malignant melanoma and its importance for tumor progression.

A novel tumor suppressor gene, PTEN/MMAC1, on 10q23, displayed a number of mutations in solid tumors as gliomas and breast cancer. Aberrations of the long arm of chromosome 10 have been frequently detected in tumor progression of malignant melanoma of the skin by a variety of methods including cytogenetic analysis, fluorescence in situ hybridization and loss of heterozygosity analysis. Compared to previous studies, which propose an involvement of PTEN/MMAC1 in malignant melanoma mostly on the basis of data derived from cell lines and metastases, we analyzed a broader spectrum of exclusively patient derived tumor tissue by PCR and direct sequencing analysis of PTEN/MMAC1. Here, we present data of 25 primary melanomas (8 superficial spreading melanomas, 17 nodular melanomas) and 25 metastases of 41 patients. Neither loss of the complete gene nor a whole exon nor any nonsense mutations could be demonstrated. However, we detected several polymorphisms and some mutations in the introns, and in two metastatic tumors mutations with an amino acid change. Our results obtained from tissue samples underline that mutations of PTEN/MMAC1 are not an essential event in the onset of malignant melanoma of the skin, but could have an impact on tumor progression.

Base Sequence↗
PubMed2000

TTC4, a novel candidate tumor suppressor gene at 1p31 is often mutated in malignant melanoma of the skin.

A novel candidate tumor suppressor gene, TTC4, on chromosome 1p31 has been described recently. Since aberrations in this region have been detected in malignant melanoma, we investigated DNA of paraffin-embedded sections from 16 typical naevi, 19 atypical naevi, 32 primary melanomas (15 superficial spreading melanomas, 17 nodular melanomas) and 25 metastases and DNA from four melanoma cell lines by PCR and direct sequencing analysis for mutations in all exons of TTC4. Tumors comprised a wide range of thickness (Breslow index) and Clark levels. No mutations could be detected in typical or atypical naevi, but we found seven different point mutations in the tumor samples, six of them causing an amino acid change. Ten melanoma samples belonging to nine patients showed one or more of these mutations. In detail, in six of 25 metastases, in two of 17 nodular melanomas and in two of 15 superficial spreading melanomas point mutations could be detected. In two cell lines, a loss of a whole exon could be demonstrated and in one cell line we found a point mutation. In addition, three polymorphisms were found. Our findings indicate that TTC4 may participate in the pathogenesis of malignant melanomas of the skin.

Amino Acid Sequence↗
PubMed2000

Mitochondrial DNA in the Central European population. Human identification with the help of the forensic mt-DNA D-loop-base database.

Sequencing of mtDNA is an advanced method for the individualisation of traces. Disadvantages of this method are expensive and time-consuming analysis and evaluation procedures as well as the necessary stock of population-genetic data which is still insufficient. Central European institutes of forensic medicine from Germany, Austria, and Switzerland have been working together since the beginning of 1998 to establish a mtDNA database. The aim is to build up a large stock of forensically established data and provide population-genetic data for frequency investigations, which will serve as a basis for expert opinions and scientific research. Good data quality is ensured by using original sequences only. Ring tests, which have been conducted to enhance analytical reliability, revealed a high correspondence rate of the analytical results obtained by the individual member institutes. Today 1410 sequences are available for comparison, of which 1285 sequences in the HV1 and HV2 regions cover the full ranges from 16051 to 16365 and from 73 to 340 (according to Anderson). The major part is formed by Central European sequences comprising 1256 data sets from Germany, Austria, and Switzerland. Today the database contains sequences from a total of 12 European, six African and three Asian countries including 100 sequences from Japan. This paper is aimed at discussing the individualisation potentials of mtDNA as well as the possibilities and limits of ethnic differentiation by means of pairwise sequence differences on the basis of the data stock available.

Austria↗
PubMed2000

First hints for a correlation between amplification of the Int-2 gene and infection with human papillomavirus in head and neck squamous cell carcinomas.

Infection with human papillomavirus (HPV) and alterations in certain genes have frequently been proposed as mechanisms in the pathogenesis of head and neck squamous cell carcinoma (HNSCC). Here, we investigated 47 HNSCC for the presence of HPV and, by fluorescence in situ hybridisation, for amplification of Int-2 and Hst-1 in the search for a possible correlation. The highest frequency of HPV infection was found in hypopharyngeal carcinomas, while amplification of Int-2 or Hst-1 was distributed more equally among the different localisations. Amplification of Int-2 was detectable (7 of 9 cases) in 78% of the HPV-positive carcinomas, whereas no virus infection could be found in the five cases with amplified Hst-1 only. In spite of the rather low number of infected tumour samples, our results suggest a correlation between HPV infection and amplification of Int-2.

Adult↗
PubMed2000

Use of interphase cytogenetics in demonstrating specific chromosomal aberrations in solid tumors--new insights in the pathogenesis of malignant melanoma and head and neck squamous cell carcinoma.

The detection of structural and numerical chromosomal aberrations is an important part of the characterization of tumors and genetic diseases. The direct demonstration of DNA sequences in interphase nuclei and metaphases by fluorescence in situ hybridization (FISH) has been termed interphase cytogenetics. It has been proven as a powerful technique to detect specific aberrations in a wide variety of cell types, including paraffin-embedded tissue. Nowadays a standard method in leukemia and lymphoma, interphase cytogenetics contributes mainly to the diagnosis in these tumors and helps to classify soft tissue tumors. Therefore FISH is mandatory for the choice of therapy in these tumors. In contrast to the aforementioned, up to now, the value of FISH in solid tumors is mostly limited to pure research and contributes in this way to our understanding of tumor biology. But with the use of paraffin-embedded tissue and the first results obtained, it seems very likely that a direct correlation between histological classification and cytogenetic characteristics of solid tumors can be achieved in the near future. This information might not only provide insights into tumor biology, but could also contribute to a different tumor classification, a sort of risk estimation, where we might predict the possible biological behavior of solid tumors. This could greatly influence further therapeutic decisions thus establishing the FISH technique as an indisputable part in the diagnosis of solid tumors.

Animals↗
PubMed1999

Significance of the small subtelomeric area of chromosome 1 (1p36.3) in the progression of malignant melanoma: FISH deletion screening with YAC DNA probes.

The short arm of chromosome 1 (1p), especially the subtelomeric region of 1p36, is a common site for abnormalities in malignant melanoma of the skin. In a recent study nodular melanomas displayed deletions of 1p36 in an augmented percentage of cases. To evaluate the dimension of these deletions and to study their significance for the progression of malignant melanoma we analyzed seven melanoma cell lines, 32 primary tumors, and 32 metastatic tumors by fluorescence in situ hybridization with the DNA probe D1Z2 in 1p36.3 and eight YAC DNA probes hybridizing to 1p36, 1p32, 1p31, and 1p21. All cell lines, 91% of the metastatic tumors and 63% of nodular melanomas showed a deletion of 1p36.3. In the YAC hybridization experiments, the most frequent deletions were found in 1p36 in all cell lines, in 13% of nodular melanoma, and in 44% of metastatic tumors. Deletions in 1p36 were mostly confined to a rather small area near the locus D1Z2. The frequent occurrence of this deletion in melanomas with a high metastatic potential and the abundant accumulation of this deletion in metastasis point to genes located on 1p36, which might be of significance for the metastatic capability of malignant melanoma.

Chromosomes, Artificial, Yeast↗
PubMed1999

Different numerical chromosomal aberrations detected by FISH in oropharyngeal, hypopharyngeal and laryngeal squamous cell carcinoma.

AIMS: Little information is available about stage- or site-specific chromosomal aberrations in head and neck squamous cell carcinoma (HNSCC). We tried to identify whether different patterns of chromosomal gain or loss in squamous cell carcinomas were associated with different stages or head and neck sites. METHODS AND RESULTS: We investigated isolated interphase cells from paraffin sections of 5 3 squamous cell carcinomas of the head and neck region by fluorescence in situ hybridization techniques. We used centromeric DNA probes for chromosomes 1, 3, 4, 6, 7, 9, 10, 11, 12, 15, 17, 18, X and Y. The majority of tumour samples showed aneuploidy for most chromosomes analysed. We were able to find differences in the chromosomal aberrations between the tumour sites and stages of the HNSCC investigated. The main numerical chromosomal abnormalities were an under-representation of chromosomes 3 (26%), 6 (17%), 9 (26%), 10 (23%) and 18 (32%). The Y chromosome was lost in 53% of male tumours. A loss of chromosomes 3 and 10 was detected mostly in laryngeal SCC (39% and 30%, respectively); the under-representation of chromosome 9 was predominantly seen in oropharyngeal SCC (54%) and a copy number decrease of chromosomes 18 was found in 57% of hypopharyngeal tumours. CONCLUSION: Although the number of tumour samples investigated is rather low, our results suggest that the different tumour sites of HNSCC may also show different patterns of chromosomal changes.

Adult↗
PubMed1998

An increased frequency of numerical chromosomal abnormalities and 1p36 deletions in isolated cells from paraffin sections of malignant melanomas by means of interphase cytogenetics.

At present, little information is available on tumor and stage-specific chromosomal aberrations in malignant melanoma. Therefore, we applied fluorescence in situ hybridization on isolated interphase cells from paraffin sections of 25 cases of malignant melanomas, comprising 17 primary tumors (PTs) and 8 metastases (MTs) in various anatomical sites. We used centromeric probes for chromosomes 1, 7, 9, 10, 11, 12, 15, 17, 18, X, and Y and a midisatellite probe localized in 1p36. Four of the PTs and 5 of the MTs showed polyploidy for all applied probes. The most frequent type of numerical aberration was an overrepresentation of chromosomes 1 (3 PTs, 5 MTs) and 7 (3 PTs, 1 MT), and an underrepresentation of chromosomes 9 (3 PTs) and 10 (6 PTs, 5 MTs). The Y chromosome was lost in all male tumors. In addition, we observed monosomy 11, 12, 15, 17 or 18, and trisomy 12 or 17. Only 1 PT showed no aberrations for any applied DNA probe. A deletion in the near-telomeric region of 1p36 was found surprisingly often (9 PTs, 7 MTs). Our results suggest that the loss of gene(s) in this region is an important event in the pathogenesis of malignant melanoma of the skin.

Adult↗
PubMed1998

A de novo translocation 46,X,t(X;15) causing haemophilia B in a girl: a case report.

Haemophilia B is an X-linked recessive bleeding disorder caused by mutations in the factor IX gene with an incidence of 1:25000-30000. Usually female carriers are clinically normal, and severe phenotypic expression of the disease in females is extremely rare. In this report we describe a girl with a clinically severe course of haemophilia B who had no signs of Turner syndrome or any other dysmorphic features. Cytogenetic and molecular studies in the patient and her parents showed a de novo translocation 46,X,t(X;15)(q27.1;p11.2) in the patient, indicating a possible break near the factor IX gene. The structurally normal X chromosome was late replicating and inactivated in all metaphases as shown by high-resolution R-banding. By fluorescence in situ hybridization (FISH) with YAC and cosmid probes we could further characterize the breakpoint region on the X chromosome and the involvement of the factor IX gene.

Adult↗
PubMed1998

Differences in chromosomal aberrations between nodular and superficial spreading malignant melanoma detected by interphase cytogenetics.

At present, little information is available on specific chromosomal aberrations in malignant melanomas of different subtypes and different growth behaviors. Therefore, we have applied fluorescence in situ hybridization on isolated interphase cells from paraffin sections of 79 primary tumors of malignant melanomas: 47 nodular melanomas and 32 superficial spreading melanomas in various stages. We used centromeric probes for the chromosomes 1, 4, 6, 7, 9, 10, 11, 12, 15, 17, 18, X, and Y and a midisatellite probe localized in 1p36. The number of chromosomal aberrations and the ploidy of the cells rose with the tumor stage in both subtypes, although in superficial spreading melanomas, fewer chromosomal abnormalities were detectable than in nodular melanomas. A deletion in 1p36 could only be found in nodular melanomas (mostly in higher tumor stages), not in superficial spreading melanomas. Our results show that the different histologic subtypes of malignant melanoma of the skin differ also in their chromosomal aberrations. In addition, it seems that there may be a correlation between the growth characteristics and putative tumor suppressor genes on 1p36.

Adult↗