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M Dietel

Publications and source records attributed to M Dietel.

At least 55 records · Page 3Linked to original sources
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

Specificity of PCR-based clonality analysis of immunoglobulin heavy chain gene rearrangements for the detection of bone marrow involvement by low-grade B-cell lymphomas.

A study was performed to investigate the utility of polymerase chain reaction (PCR)-based analysis of immunoglobulin heavy chain (IgH) gene rearrangements for the diagnosis of low-grade malignant B-cell lymphomas on formalin-fixed, EDTA-decalcified, and paraffin-embedded bone marrow trephine biopsies. On amplifying two DNA samples per biopsy, no reproducible monoclonal PCR result was found in 32 patients with reactive lymphoid hyperplasias. In contrast, 5/14 patients with known low-grade B-cell lymphomas, but histomorphologically and immunohistochemically lymphoma-free bone marrow, showed a reproducible monoclonal IgH gene rearrangement. In three of these cases, sequence analysis revealed completely different amplification products on comparing bone marrow and lymph node infiltrations, while in the other two cases the products were identical. In one of the latter biopsies, an unequivocal lymphoma infiltrate was found after step sectioning of the biopsy, while the other case remained lymphoma-free according to conventional criteria. A third group of three patients with known lymphomas and bone marrow findings that were suggestive but not diagnostic of bone marrow involvement showed monoclonal PCR results in all three cases, with identical sequences in bone marrow and extramedullary lymphoma infiltrates. These data suggest that a reproducible monoclonal IgH gene rearrangement is highly specific for the presence of malignant B-cells in bone marrow. In staging procedures for low-grade B-cell lymphomas, PCR yields no additional information in cases that are morphologically and immunohistochemically lymphoma-free after evaluation of representative sections. PCR may be useful in equivocal cases, provided that IgH gene rearrangements of extramedullary lymphoma and bone marrow are sequenced and compared.

Adult↗
PubMed2000

Pathologic correlation of sonographic echogenic foci in the fetal heart.

The goal of the current paper is to present, on the basis of six investigated fetal hearts, the pathological substrate of prenatally, sonographically diagnosed echogenic intramyocardial foci. The right ventricle, left ventricle, interventricular septum and papillary muscles of both ventricles of six hearts of the fetuses of high-risk pregnant women showing sonographically diagnosed intramyocardial echogenic foci were investigated. At termination of pregnancy all the women were between the 20th and the 24th week of gestation. Of the six cases, four were induced abortions and two were spontaneous abortions. For the control group we investigated the hearts of two fetuses without heart defects at the 22nd and 23rd week of gestation which had proven extracardial anomalies and a normal karyotype. Both cases were induced abortions which prenatally showed no echogenic cardiac foci. In all eight cases a prenatal karyotyping was performed. In the six cases with echogenic foci the location and number of the foci were determined both prenatally and by means of histologic sections; the size of the foci was measured as well. Histological staining was with routine haematoxylin-eosin; Masson-Goldner was used for connective tissue; Kossa for calcification; and Berlin blue for haemosiderin. Histologically, in all six cases, intramyocardial calcifications surrounded by fibrotic tissue were in: papillary muscle of the left ventricle in six cases; papillary muscle of the right ventricle in one case; and the subendocardial myocardium of the right ventricle in one case. Four cases had one, one case had two and one case had three calcified foci. Three cases had cardiac and two cases had extracardiac anomalies. Four cases had chromosome anomalies: two were trisomy 21, one trisomy 13 and one triploidy. The remaining two cases had a normal karyotype. No case showed pathological changes of the chordae tendinae, myocardial cell necrosis or inflammation. There were no patho-morphological differences between the intramyocardial calcifications of the papillary muscles in cases with chromosome anomalies and with normal karyotype. As the patho-morphological correlate of the sonographically diagnosed echogenic foci, histological investigation on all six fetal hearts showed coarse intramyocardial calcifications surrounded by myocardial fibrosis. Conventional histological methods gave no indication of the cause of the intramyocardial calcifications.

Abortion, Induced↗
PubMed2000

Identification of novel proteins associated with the development of chemoresistance in malignant melanoma using two-dimensional electrophoresis.

A model system for studying chemoresistance in human melanoma cells (MeWo) has been established utilizing the four commonly used cytotoxic drugs vindesine, cisplatin, fotemustine and etoposide to yield stable drug-resistant sublines. We analyzed phenotypical differences between MeWo cells and their chemoresistant counterparts using two-dimensional electrophoresis. Proteins that were overexpressed in chemoresistant cell lines were purified and identified using matrix assisted laser desorption/ionization-time of flight - mass spectrometry (MALDI-TOF-MS) and microsequencing. Here we show that four proteins, namely the translationally controlled tumor protein, the human elongation factor 1-delta, tetratricopeptide repeat protein and the isoform 14-3-3-gamma of the 14-3-3-family are overexpressed in chemoresistant melanoma cell lines. The significance of these findings is now being verified using transfection experiments with the aim of developing more effective chemotherapy protocols.

Drug Resistance, Neoplasm↗
PubMed2000

Bone marrow microvessel density is a prognostic factor for survival in patients with multiple myeloma.

The importance of neoangiogenesis for the progressive growth and viability of solid tumors is well established. Recently, there has been growing evidence that angiogenesis might also be important in hematological malignancies, but only few data are available. In this report, we have studied the impact of bone marrow microvessel density and survival in patients with multiple myeloma (MM). Immunohistochemical CD34 stained paraffin-embedded bone marrow biopsies of 44 patients with newly diagnosed MM were studied. Microvessels were counted in 400 x magnification and the mean number of vessels per area in each sample was noted as the microvessel density (MVD). The median MVD was 48 vessels/mm2, the range was 0-125 vessels/mm2. Using a cut-off value of the median MVD in the Kaplan-Meier analysis, the median survival was 22.2 months in the group with the higher MVD and was not reached in the group with the lower MVD (P< 0.01). In a multivariate Cox regression analysis, using previously identified prognostic factors beta2-microglobulin, C-reactive protein (CRP), and age, MVD remained significant as a prognostic factor (P< 0.03).

Adult↗
PubMed2000

An unusual case of leukemic non-Hodgkin's lymphoma with blastic transformation.

We report on a patient who was diagnosed as having B-cell chronic lymphocytic leukemia (CLL) with atypical morphology. Flow cytometry disclosed CD5, CD19, and CD23 positivity, an immunophenotype seen mostly in B-CLL. Histology of the spleen and bone marrow suggested a diagnosis of small lymphocytic lymphoma. Upon blastic transformation, only 3 years after the diagnosis had been made, unusual clinical and laboratory features emerged. Lymphoid blasts appeared in the peripheral blood, and the patient developed nodular infiltrates consisting of these blasts at recent venous puncture sites. The patient did not respond to chemotherapy and died. The lymphoid blasts in the peripheral blood were CD5-, CD19+, and CD23+ and harbored t(11;14) (q13;q32) and t(11;21)(p11;q21) translocations. To account for the possibility of two independent lymphoid malignancies, molecular genetic analyses were performed on samples from the spleen, bone marrow and a lymph node with the large-cell lymphoma, which showed identical clones in these tissues. This unusual case supports the idea that in leukemic non-Hodgkin's lymphoma, in addition to morphology, an accurate diagnostic workup requires immunophenotypic, cytogenetic, and molecular studies.

CD5 Antigens↗
PubMed2000

[PCR based diagnosis in pathology].

PCR-based diagnosis of infectious diseases has developed into an important method in surgical pathology. We summarize our experience in this area based on 3500 analyses performed during the past 5 years. The peculiarity of material from a pathological laboratory is the risk of DNA fragmentation as a consequence of tissue fixation. For this reason the assays used must be adapted to this particular situation. PCR-based diagnosis of infectious diseases, if performed according to appropriate quality standards, is a safe and effective technique with high sensitivity and specificity and results in an etiologically based diagnosis.

Humans↗
PubMed2000

[Autopsy techniques in congenital heart defects. Influence of prenatal diagnosis on the planning and carrying out of autopsies].

As a result of the quality of prenatal ultrasound and the expanded experience of prenatal diagnosticians, it is possible to observe congenital heart malformations in increasingly greater detail and at an ever earlier stage of gestation [4]. Since it is on the basis of ultrasound findings that decisions to terminate pregnancies are made, it is of cardinal importance that after termination monitoring and confirmation of the prenatal diagnosis be carried out. This need can only be adequately met by autopsy. There are different methods for carrying out autopsies when there is suspicion of a congenital heart defect: a) the Anderson sequential segmental analysis as modified according to the Berlin method; b) use of a special autoptic method corresponding to the ultrasound findings, based on defining a preferred sectional plane; c) stereomicroscopically; or d) microscopically after embedding and preparation of serial microscopic sections. For the pathologist the consequence is that he has to adapt his autopsy method to the ultrasound findings and the age of the fetus. This enables him to determine an optimal, case-based autopsy strategy for each type of cardiac defect, which is essential for monitoring of the prenatal diagnosis. The present paper discusses the various autoptic methods used in cases of congenital heart malformations and the consequences for the pathologist of the continuing improvements in prenatal diagnostics.

Autopsy↗
PubMed2000

Serous tumors of low malignant potential of the ovary. 1. Diagnostic pathology.

Serous ovarian tumors of low malignant potential (SLMP)--also called borderline tumors of the ovary--represent a heterogeneous group of ovarian epithelial neoplasms. In general, this tumor type has a favorable prognosis. Nevertheless, 10-20% of SLMP exhibit a progressively worsening clinical course, with widespread peritoneal implants and death of the patient within 5 years. The criteria for recognizing the SLMP with an unfavorable prognosis and for distinguishing SLMP from highly differentiated ovarian carcinomas are summarized in this report. The importance of supporting methods, e.g., DNA cytophotometry, is demonstrated, revealing that in most cases aneuploidy can be regarded as an indicator for aggressiveness of the tumor and for poor clinical outcome. The importance of the new concept of micropapillary serous carcinomas (MPSC), the relationship of this variant of SLMP to invasive serous carcinomas, and the prognostic importance of invasive vs noninvasive peritoneal implants are discussed. (The concepts of molecular pathology of SLMP will be discussed in part 2 of this serial paper.)

Aneuploidy↗
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

Effect of the breast-cancer resistance protein on atypical multidrug resistance.

Simultaneous resistance of malignant cells to several antineoplastic agents that are structurally and functionally unrelated is known as multidrug resistance. It is one of the main causes of chemotherapy failure. Besides the classic multidrug-resistant phenotype, mediated by increased activity of the ATP-binding cassette (ABC) transporter P-glycoprotein, there are other multidrug-resistant tumours, with resistance caused by different mechanisms. This is called atypical multidrug resistance. Pronounced overexpression of a novel ABC transporter has been observed in various human cancer cell lines with atypical multidrug resistance (which were established by in vitro exposure to mitoxantrone, topotecan, doxorubicin, or bisantrene). This novel transporter was originally named breast-cancer resistance protein (BCRP). BCRP is a 655-aminoacid protein of about 72 kDa. It can be thought of as an ABC 'half-transporter', and it forms dimers to produce an active transport complex. Transfection experiments with BCRP cDNA showed that the phenotype of atypical multidrug resistance could be transferred to formerly drug-sensitive cancer cells. Although the role of BCRP in drug resistance of clinical cancers is still unclear, preliminary data obtained by mRNA and protein expression analyses support the assumption that it has a role in clinical multidrug resistance.

ATP Binding Cassette Transporter, Subfamily G, Mem↗
PubMed2000

Thyroid transcription factor-1 is the superior immunohistochemical marker for pulmonary adenocarcinomas and large cell carcinomas compared to surfactant proteins A and B.

AIMS: Antibodies against the thyroid transcription factor-1 (TTF-1) and the surfactant proteins A and B (SPA, SPB) were compared as paraffin-reactive immunohistochemical markers for non-small cell carcinomas of pulmonary origin. METHODS AND RESULTS: We studied 138 carcinomas of pulmonary origin (98 adenocarcinomas, 20 non-neuroendocrine large cell carcinomas, 20 squamous cell carcinomas) and a total of 276 extrapulmonary carcinomas of various primary origins. Using the monoclonal antibody 8G7G3/1, TTF-1 was detectable in 75% of non-mucinous pulmonary adenocarcinomas and in 40% of large cell carcinomas but in only 10% of mucinous adenocarcinomas and not in squamous cell carcinomas. In contrast, both SPA and SPB were positive in only 45% of pulmonary adenocarcinomas and in 10% and in 5% of the large cell carcinomas, respectively. TTF-1 had a specificity of 0.98 for pulmonary carcinomas as 5/7 thyroid carcinomas were the only TTF-1-positive extrapulmonary tumours. Anti-SPB and anti-SPA had specificities of 1. 00 and 0.97, respectively. CONCLUSIONS: The monoclonal antibody 8G7G3/1 against TTF-1 should be the first choice as a component of an antibody panel aiming to prove or to exclude the pulmonary origin of non-mucinous adenocarcinomas and non-neuroendocrine poorly differentiated carcinomas, especially in patients presenting with metastatic carcinomas of unknown primary site.

Adenocarcinoma↗
PubMed2000

Expression of thyroid transcription factor-1 in pulmonary and extrapulmonary small cell carcinomas and other neuroendocrine carcinomas of various primary sites.

AIMS: The thyroid transcription factor-1 (TTF-1) is a highly specific immunohistochemical marker for the identification of pulmonary adenocarcinomas and non-neuroendocrine large cell carcinomas, especially in patients presenting with metastatic carcinomas of unknown primary site. In this study we tested if anti-TTF-1 can also be used to verify a pulmonary origin of neuroendocrine carcinomas, placing emphasis on the discrimination of pulmonary small cell carcinomas (SCCs) from extrapulmonary SCCs and the distinction of SCCs from Merkel cell carcinomas of the skin. METHODS AND RESULTS: We studied 37 pulmonary SCCs, 15 SCCs of extrapulmonary origin, 4 pulmonary large cell neuroendocrine carcinomas (LCNECs), four extrapulmonary LCNECs, six medullary thyroid carcinomas, 16 Merkel cell carcinomas, and a total of 32 carcinoids/low-grade neuroendocrine carcinomas of pulmonary (12 cases) and extrapulmonary (20 cases) origin. Using the commercially available monoclonal antibody 8G7G3/1, TTF-1 was immunohistochemically detectable in 81% of pulmonary SCCs but also in 80% of extrapulmonary SCCs. Furthermore, anti-TTF-1 showed a positive staining in 50% of all pulmonary carcinoids, in one gastric carcinoid, in 2/4 of pulmonary, and 1/4 of extrapulmonary LCNECs. All medullary thyroid carcinomas were also TTF-1-positive. Merkel cell carcinomas were consistently TTF-1-negative. CONCLUSIONS: Our results suggest that in contrast to non-neuroendocrine carcinomas, anti-TTF-1 cannot be used to prove or to exclude a pulmonary origin of SCCs or LCNECs of unknown or uncertain primary site. Therefore, before using anti-TTF-1 as a marker for pulmonary carcinomas one should be sure to have excluded SCC and LCNEC. On the other hand, anti-TTF-1 might be used to specifically discriminate SCCs of various origin from Merkel cell carcinomas.

Antibodies, Monoclonal↗
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

Modulation of DNA topoisomerase II activity and expression in melanoma cells with acquired drug resistance.

The role of DNA topoisomerases (Topo) IIalpha and IIbeta was investigated in various drug-resistant melanoma cells. Melanoma cells resistant to etoposide, exhibited an up to tenfold reduced Topo II activity corresponding to an increasing degree of drug resistance indicating that modulation of Topo II activity contribute to the drug-resistant phenotype. The reduction of Topo II activity was reflected by decreased nuclear amounts of both Topo II isoforms.

Antineoplastic Agents, Phytogenic↗
PubMed2000

Comparison of different telepathology solutions for primary frozen section diagnostic.

In a retrospective study on a set of 125 cases we compared the following three telepathology solutions for primary frozen section diagnosis: ATM-TP (connection via ATM), TPS 1.0 (connection via LAN) and TELEMIC (connection via Internet), which represent different concepts of telepathological procedures. A set of 125 routine frozen sections (breast) was selected from the Charité cases of the year 1999. Four experienced pathologists diagnosed retrospectively all of these cases using the ATM-TP and TPS systems and 53 of them with the TELEMIC system. Using the ATM-TP we recorded no false positive (0%), 4 false negative (3.2%) and 4 deferred (3.2%) cases. Using the TPS we recorded no false positive (0%), 4 false negative (3.2%) and 4 deferred (3.2%) cases. Using the TELEMIC we recorded in 53 cases no false positive (0%), no false negative (0%) and 16 deferred (30.2%) cases. The average time of 2.2 minutes per case using ATM-TP is also short enough for routine frozen section diagnostic. This is also true for the TPS system with 7.2 minutes per case.

Breast Neoplasms↗