PubMed Health⌕ Search

Biomedical subjects

M Debiec-Rychter

Publications and source records attributed to M Debiec-Rychter.

At least 55 records · Page 3Linked to original sources
PubMed1999

Cytogenetic and proliferative potentials in meningiomas.

Cytogenetic analysis and Ki-67 staining index (SI) were performed on the series of 51 meningiomas, to estimate the relationship between the extent of chromosomal changes and the growth potential of tumors. The tumors were classified according to histological subtype (22 meningiotheliomatous, 15 transitional, 12 fibroblastic and 2 angiomatous) and grade (40 benign, 5 atypical and 6 malignant ones). There was no significant difference in the complexity of chromosomal changes among the histologically distinct tumor subtypes. In contrast, there was a significant association between the number of chromosomal abnormalities and tumor grade. Normal karyotypes were found in 50% and complex in 20% of benign tumors. All grade II or III tumors revealed complex karotype. The tumors classified as benign revealed significantly lower mean Ki-67 SI than atypical or malignant ones (1.6%, 7.4% and 14.7%, respectively). However, within tumors classified as benign, mean Ki-67 SI of these with normal or simple karyotypic changes did not differ significantly from those with complex karyotype (1.6% and 0.9%, respectively). Thus, the extent of genome abnormalities in meningiomas, measured on the chromosomal level, does not relate directly to their proliferative potential.

Adolescent↗
PubMed1998

Recurrent chromosome changes in two adult fibrosarcomas.

Cytogenetic analysis of two adult fibrosarcomas revealed clonal chromosomal rearrangements including unbalanced translocations between chromosomes 2 and 19, with the same segment, 2q21-qter, translocated onto 19p13 in one tumor and 19q13 in another; and partial monosomy of 10q due to add(10)(q22) and del(10)(q22q25) seen in one tumor each. This is the first description of nonrandom chromosomal changes in adult fibrosarcoma.

Adolescent↗
PubMed1998

DNA adduct formation in human and rat mammary epithelium by N-hydroxy derivatives of 2-aminofluorene and 4-aminobiphenyl.

Primary cultures of rat mammary epithelium and the human mammary cell line MCF-12 were incubated with 10 microM N-formyl-, N-acetyl-, or N-propionyl-derivatives of N-hydroxy-2-aminofluorene (N-OH-AF) or N-formyl-, or N-acetyl derivatives of N-hydroxy-4-aminobiphenyl (N-OH-ABP), in the medium with or without 100 microM paraoxon, for 3 h. Carcinogen-DNA adducts in the nuclei were detected with an immunohistochemical method using polyclonal antibodies against N-(deoxyguano-8-yl)-2-aminofluorene and ABP-DNA adducts. The relative amounts of adducts per nucleus were determined by image analysis. After treatment, more than 90% of the cells that were attached on the coverslip were alive, as determined by the trypan blue exclusion. All carcinogens produced adducts in both human and rat cells. Adduct formation by the formyl, but not the acetyl or porpionyl, derivatives was inhibited up to 65% by paraoxon. These results demonstrate that both acetyl and propionyl derivatives are primarily activated by cytosolic acetyltransferases and the formyl derivatives may be equally activated by the acetyltransferases and microsomal carboxylesterases. Additionally, the results suggest that exposure to aromatic amines may be a risk factor for human breast cancer.

Aminobiphenyl Compounds↗
PubMed1998

Mutations of TP53, amplification of EGFR, MDM2 and CDK4, and deletions of CDKN2A in malignant astrocytomas.

We investigated the frequency and mutual relationship of molecular alterations in 33 malignant astrocytomas (28 glioblastomas and 5 anaplastic astrocytomas). The genetic alterations analyzed were: deletion of CDKN2a/p16 gene, TP53 mutations, and amplification of EGFR, MDM2 and CDK4. The most common genetic alteration was EGFR amplification which was revealed in 15 cases (45%). TP53 mutation was identified in 9 cases (27%) and CDKN2/p16 deletion was detected in 13 cases (41%). Either MDM2 and CDK4 amplifications were less frequent, as they were identified in 4 (12%) and 1 (3%) case, respectively. Of the 15 cases showing the amplification of EGFR, 9 had CDKN2/p16 deletion (60%, p = 0.04). On the other hand, CDKN2/p16 deletion and EGFR amplification rarely occurred with TP53 mutations (2 of 14 cases with CDKN2/p16 deletion, 14%). These results confirm the existence of at least two different pathways leading to the formation of a glioblastoma.

Cyclin-Dependent Kinase 4↗
PubMed1998

Biologic heterogeneity of angiomatous meningiomas.

Three angiomatous meningiomas, classified histologically as benign, were analyzed cytogenetically and examined for the expression of EGF/PDGF and their receptors by immunohistochemistry. An accumulation of p53 protein and the presence of mutations in exons 5-8 of the p53 gene in neoplastic cells were also determined. In one tumour, chromosome studies revealed near diploid karyotype with the loss of chromosome 22. Two other meningiomas revealed tetraploid karyotypes with the presence of telomeric associations and a wide spectrum of numerical, complex chromosome aberrations. Moderate EGF and EGFR immunoreactivity was found in three and one meningioma, respectively. All tumours exhibited diffuse PDGF and PDGFR-beta expression. No p53 gene mutations were found, but one tumour expressed strong and dispersed p53 immunopositivity. This findings reflect the biological heterogeneity of angiomatous meningiomas.

Adult↗
PubMed1998

Immunohistochemical status of p53, mdm2 and Ki-67 in malignant fibrous histiocytoma.

The aim of the study was to evaluate the frequency of p53, mdm2 and Ki-67 immunopositivity in MFH, and to investigate possible associations of their expression with the grade of malignancy and predominant histological pattern--storiform, pleomorphic and myxoid subtype of MFH. A total number of 51 tumor samples from 21 primary and 30 secondary MFHs was studied using monoclonal anti-p53 (DO-78, DAKO), anti-mdm2 (1F2, NOVOCASTRA) and polyclonal anti-Ki-67 (DAKO) antibodies. The p53 immunopositivity was observed in 32.7% of all tumor samples (in 36.8% of primary and in 30% of recurrent and metastatic tumors). The mdm2 immunopositivity was noted in 34.8% of all tumor samples (in 33.3% of primary and 35.7% of secondary tumors). The mean percentage of p53, mdm2 and Ki-67 positive cells was 15.5, 8.8 and 7.05, respectively. The mean Ki-67 LI was statistically higher in grade 3 than in grade 2 of malignancy (p = 0.006). A significant correlation was found between mdm2 positivity and histological subtypes of MFH--storiform and pleomorphic types were more frequently mdm2 positive than myxoid variant (p = 0.035 and p = 0.009, respectively). No such correlation was observed for p53 positivity of tumors and subtypes, but there was a statistically significant difference in the percentage of p53 positive cells between storiform and myxoid type (p = 0.049). We also noted more tumors expressing high percentage (over 20%) of mdm2 positive cells in pleomorphic and storiform subtypes than in myxoid variant (p = 0.048). The Ki-67 LI was also higher in pleomorphic than in other types of MFH (p = 0.012). A strong positive correlation was found between p53 positivity and mdm2 positivity of tumors in primary MFHs (p = 0.00146). p53 and mdm2 positive tumors were mainly in grade 3 of malignancy, but no statistically significant correlations were noted. A positive correlation between the percentage of p53 positive cells and Ki-67 positive cells (p = 0.0028) was observed.

Histiocytoma, Benign Fibrous↗
PubMed1998

Detection of the SYT-SSX fusion transcripts in formaldehyde-fixed, paraffin-embedded tissue: a reverse transcription polymerase chain reaction amplification assay useful in the diagnosis of synovial sarcoma.

Identification of the t(X;18)(p11.2;q11.2) translocation and detection of the resulting SYT-SSX1 or SYT-SSX2 fusion transcripts are useful diagnostic markers for synovial sarcoma. In this study, we developed a polymerase chain reaction (PCR) assay to amplify SYT-SSX fusion transcripts. The primer sequences were designed to generate small PCR products and to amplify sequences of all known SSX genes as fusion partners for the SYT gene. RNA was obtained from formaldehyde-fixed and paraffin-embedded tissues of 22 immunohistochemically characterized synovial sarcomas, 6 of them cytogenetically confirmed as t(X;18) positive. The SYT-SSX fusion transcripts were detected in 21 of the 22 analyzed cases. The type of the fusion was identified by the specific restriction enzyme digestion pattern as SYT-SSX1 in 13 cases and SYT-SSX2 in 7 cases; in 1 case, the type could not be assigned. None of the cases showed involvement of the SSX3, SSX4, or SSX5 genes, the other members of the SSX gene family. In seven cases, the SYT-SSX1 or SYT-SSX2 fusion transcripts were demonstrated in frozen tissue using a different PCR assay. The PCR products were confirmed as SYT-SSX sequences by sequencing in five randomly selected cases. Fifteen other sarcomas and related tumors were negative for SYT-SSX fusion transcripts. The PCR assay used in this study performs well in formaldehyde-fixed and paraffin-embedded tissue, and it shows a high specificity. This assay can be used as an adjunct test for diagnostically difficult cases or in retrospective studies to refine the diagnosis of synovial sarcoma in archival material.

Adolescent↗
PubMed1998

A comparative study of epidermal growth factor receptor (EGFR) and MDM2 gene amplification and protein immunoreactivity in human glioblastomas.

The gene of epidermal growth factor receptor (EGFR) is often altered in human astrocytomas and its amplification, rearrangement and overexpression occur almost exclusively in high grade tumours (glioblastomas). MDM2 gene is amplified in a small proportion of glioblastomas, and MDM2 immunoreactivity has also been found in this group. However, the relation between gene amplification and protein overexpression depends on several factors. Thus, the study on mutual relationship between these events needs to be clarified. In a series of 28 glioblastomas, we analysed MDM2 and EGFR gene amplification by differential PCR and protein overexpression was evaluated by immunohistochemistry. Thirteen cases (45%) presented immunopositivity for EGFR. A significant amplification of EGFR gene (the EGFR/SOD ratio above the control value +/- 3 SD) was observed in 9 tumours among which, one revealed no EGFR-immunopositivity. Three tumours displayed the ratio +/- 2-3 SD but these tumours also presented immunoreactivity for EGFR. Two other glioblastomas, with weak EGFR-expression, showed no gene amplification. The immunohistochemical staining for MDM2 revealed strong positivity only in one case, and this tumour also presented MDM2 gene amplification. On the contrary, another tumour which showed MDM2 gene amplification showed no MDM2 immunopositivity. In conclusion, our results demonstrate that there is no strict correlation between gene amplification at the DNA level and protein overexpression.

ErbB Receptors↗
PubMed1997

Role of acetyltransferases in the metabolism and carcinogenicity of aromatic amines.

The genotoxicity of N-substituted aryl compounds is dependent on their conversion to reactive metabolites, frequently through the production of reactive N-acetoxyarylamines. This activation is accomplished by acetyltransferases that are widely distributed. In the rat, the production of N-acetoxyarylamines has been most clearly related to the induction of tumors in the mammary gland, but this pathway also appears to be an important factor in the production of tumors in the liver, Zymbal gland and gastrointestinal tract. Expression of rat acetyltransferases responsible for acetylation of the nitrogen and the oxygen of arylamine derivatives (i.e., acetyltransferases 1 and 2) in bacterial cells has now permitted experiments which demonstrate that these enzymes exhibit good affinities for and N-acetylation of the endogenous arylalkylamines derived from tryptophan, i.e., tryptamine, 5-hydroxytryptamine (serotonin) and 5-methoxytryptamine, the immediate metabolic precursor of melatonin. Evidence that these reactions are likely to reflect real biological potentials is bolstered by histological localization of acetyltransferase mRNAs with synthetic antisense oligodeoxynucleotide probes. The results of these studies in rat indicate that the expression of acetyltransferase in tissues of the central nervous, gastrointestinal, urinary and reproductive systems is highly regulated, as it is in other organs commonly associated with aromatic amine carcinogenicity. Similar experimental approaches have been successful with human liver, mammary gland, kidney and bladder preparations. These observations give evidence that genotoxic N-acetoxyarylamines are produced by acetyltransferases that can metabolize, and possibly modulate, the hormonal and neurotransmitter effects of endogenous arylalkylamines. These relationships may help explain the occasional induction of tumors in organs not usually considered as targets of aromatic amines, as well as raise the possibility that the production of N-oxidized endogenous substrates may represent a mechanism for tumor induction in the absence of exogenous carcinogens.

Acetylation↗
PubMed1997

TP53 mutations in malignant astrocytomas.

Astrocytomas are the most common tumors of the central nervous system (CNS). Their malignant counterparts, anaplastic astrocytoma and glioblastoma, are lethal neoplasms with poor clinical outcome and they frequently carry mutations of TP53 tumor suppressor gene. In order to determine the frequency and type of this molecular alteration in the Polish population, we analyzed the polymerase chain reaction products corresponding to the most conservative exons 5-8 for single-strand conformation polymorphism and confirmed the presence of mutations by direct DNA sequencing. We identified mutations in one of five (20%) anaplastic astrocytomas and in eight of 28 (29%) glioblastomas; the mutations were most frequently identified in the exon 8 (six glioblastomas). The frequency of TP53 mutations is thus similar to the corresponding data from other studies, and the type of mutations suggests the participation of endogenous etiological factor.

Adolescent↗
PubMed1996

Histological localization of messenger RNAs for rat acetyltransferases that acetylate serotonin and genotoxic arylamines.

Rat acetyltransferases (ATs) can acetylate the endogenous arylalkylamines tryptamine, 5-hydroxytryptamine (serotonin), and 5-methoxytryptamine, the immediate precursor of melatonin. The same enzymes also acetylate and activate exogenous, carcinogenic arylamines, thereby being immediately responsible for the generation of DNA adducts. Localization of AT transcripts in the pineal gland and in specific cells of the intestine, cerebral cortex, pituitary, and lung identifies cells that may be important to the neurotransmitter and hormonal roles of the tryptamine derivatives. Transcript localization i liver, mammary gland, Zymbal gland, kidney, forestomach, and bladder, as well as intestine and lung, identifies cells that may be at increased carcinogenic risk because they can convert N-hydroxylated arylamines to genotoxic metabolites. Highly specific expression is also observed in the reproductive organs of both the male and female, including the testes, epididymis, uterus, ovary, and fallopian tube. In addition to these diverse organs, which are consistent with possible roles of the enzyme in carcinogen metabolism, neurotransmission, or hormonal regulation, specific cells of the cornea, cilliary process of the eye, olfactory process, adrenal gland, exorbital lacrimal gland, and skin also exhibit highly specific expression of AT mRNAs for which one can only speculate as to their function. In virtually every case, the extent of labeling suggested that AT1 was expressed at levels that were orders of magnitude higher than those of AT2. Qualitative differences in the sites of mRNA of these two enzymes were seen only in the olfactory process, in which AT1 was expressed in both respiratory and olfactory epithelia as well as Bowman's cells, and AT2 was detected only in the latter cells. The available data support the conclusion that the ATs are likely to be involved both in the metabolic activation of exogenous carcinogenic amines as well as the metabolism of endogenous arylalkylamines that play important hormonal and neurotransmitter roles.

Acetylation↗
PubMed1996

Comparative evaluation of p53-protein expression and the PCNA and Ki-67 proliferating cell indices in human astrocytomas.

Mutations of the p53 gene are one of the most frequent genomic alterations of human tumours of astrocytic lineage. Because the physiological role of this gene is a suppression of cellular proliferation and growth, the overexpression of p53-protein may correlate with the expression of PCNA or Ki-67, established markers of cell proliferation. Paraffin-embedded surgical specimens from 60 human astrocytomas (9 pilocytic tumours, 12 WHO grade II, 9 anaplastic astrocytomas [WHO grade III] and 30 glioblastomas [WHO grade IV]) were stained with anti-PCNA (PC10), anti-p53(DO-7) and anti-Ki-67 antibodies (DAKO). Approximately 40% of all the cases were p53-protein immunopositive (53.3% glioblastomas, 33.3% anaplastic, 41.7% low grade astrocytomas but no pilocytic tumor). Statistical analysis did not reveal statistically significant correlation between p53-immunopositivity and PCNA or Ki-67 labeling indices. The Ki-67- and PCNA LI-s were statistically correlated, and the former better discriminated groups of different grades of malignancy.

Antigens, Neoplasm↗
PubMed1996

The immunohistochemistry and ultrastructure of ganglioglioma with chromosomal alterations: a case report.

Ganglioglioma, together with its counterparts-ganglioneuroma and gangliocytoma are relatively uncommon neoplasms of the brain composed of neoplastic neurons (ganglion and ganglioid cells) and glial cells. We report here a case of ganglioglioma studied by electron microscopy. The case was further characterized by peculiar chromosomal alterations, 46,XX[6]/43,XX[1], der(1)t(1;5)(q21;q12), der(8;13)(q10;q10),-9,i(10)(q10). Routine light microscopy revealed mixed neuro-glial tumor composed of pilocytic astrocytes with abundant Rosenthal fibers and relatively numerous ganglion cells. The latter were immunoreactive with antibodies (Abs) against synaptophysin and neurofilament protein (NFP). Anti-NFP Abs also immunostained numerous distorted axons embedded in the tumor mass. Some of these showed bullous swellings and thus were analogous to dystrophic neurites or spheroids. Ganglion cells were characterized by abundant intracytoplasmic dense-core vesicles, absence of intermediate filaments and numerous microtubules. Occasionally a close apposition of ganglion cells and Rosenthal fibers were seen. Dense-cored vesicles were pleomorphic and ranged in diameter from small synaptic vesicles to large lysosome-like neurosecretory granules. The former occasionally formed characteristic dumbbell shapes. Neoplastic astrocytes were identical to those of other glial tumors of astrocytic lineage; numerous Rosenthal fibers were frequently seen.

Brain Neoplasms↗
PubMed1995

Recurrent anaplastic ependymoma with an abnormal karyotype and c-myc proto-oncogene overexpression.

Cytogenetic analysis on a supratentorial, recurrent, anaplastic ependymoma from a 29-year-old female disclosed the presence of an abnormal clone with the karyotype 46,XX,der(8)t(8;11)(q24;p11),-11,add(?)t(?;11)(?;q13). By the Northern hybridization assay and immunohistochemical staining, tumor cells revealed overexpression of c-myc proto-oncogene, although no evidence of amplification or structural rearrangement of this gene was found.

Adult↗
PubMed1995

Accumulation of chromosomal changes in human glioma progression. A cytogenetic study of 50 cases.

Cytogenetic studies of 50 human gliomas, including three oligodendrogliomas, 16 grade I-III astrocytomas, and 31 glioblastomas multiforme, were performed using the short-term tissue culture method. The most common numerical chromosome aberrations were +7, -9, -10, -14, and loss of a sex chromosome. Structural changes involved predominantly the following chromosome arms: 1q, 2q, 6q, 7q, 9p, 14q, 17p, and 18p. Losses of chromosomes 9, 10, and 14, often occurring simultaneously and in polyploid clones, were observed almost exclusively in high-grade gliomas, and appear to constitute important events during glioma progression.

Adolescent↗
PubMed1995

Cytogenetic and immunohistochemical profile of myxoid liposarcoma.

Cytogenetic and immunohistochemical studies were performed in nine myxoid liposarcomas. The tumor karyotype was determined after short-term culture of cells in vitro. Immunohistochemical studies were performed on frozen tissue in five cases and on paraffin-embedded tissue in three cases. Chromosomal analysis demonstrated a balanced translocation t(12;16) (q13;p11) as the sole abnormality in four cases. Two cases showed an association with other abnormalities. Three tumors showed variants of the t(12;16) translocation involving other chromosomes. In all cases studied, the 12q13 breakpoint was involved in rearrangements. In the majority of cases, immunohistochemical studies demonstrated vimentin (9 of 9) and S-100 protein (8 of 9). Strong focal expression of desmin was observed in two tumors. Weak focal expression was observed in three tumors. Two tumors, which were both desmin positive, showed focal expression of MSA and alpha-SMA. Strong expression of CD36 was present in all four cases that were studied for this marker. CD34 was negative in tumor cells, but it highlighted an intricate capillary network in the tumor. Close relationship between the tumor cells and pericapillary pericytes was demonstrated with CD34 and alpha-SMA strains. The authors conclude that myxoid liposarcoma is characterized by a specific chromosomal rearrangement. Its immunohistochemical profile is wider than previously believed, including expression of muscle markers.

Adult↗
PubMed1994

Mutation and altered expression of p53 genes in experimental rat bladder tumor cells.

p53 genes were analyzed for mutations and expression in a series of 24 tumors or hyperplastic lesions of the urinary bladder induced in F344 rats by carcinogen treatment. Of these, 18 were analyzed as short-term urothelial cultures. Polymerase chain reaction-single-strand conformation polymorphism analysis and DNA sequencing were used to detect alterations in p53 genes or cDNAs, and the relative amounts of p53 protein per cell were estimated by immunohistochemical staining. Missense substitutions were found in the exon 5-9 region of two of five cell cultures analyzed from lesions induced by the bladder carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine. One of these was a papillary nodular hyperplasia, indicating that p53 mutations can be present in low- as well as high-stage/grade bladder lesions. p53 mutations were not found in the exon 5-9 region in cells of any of eight bladder lesions induced by N-[4-(5-nitro-2-furyl)-2- thiazoly]formamide (FANFT), including five transitional cell carcinomas (TCCs), or either of two TCCs induced by N-methylnitrosourea. Two of nine TCCs induced by the N-glucuronide of N-hydroxy-2-aminofluorene were found to have p53 mutations. One of these was evidently altered by three genetic events: a missense substitution in exon 8, a nonsense mutation in exon 6, and silencing of the "nonsense" allele (i.e., only the p53 missense mutation was detected). Immunohistochemical analysis with monoclonal antibody PAb240 (which preferentially binds to mutant p53 protein) detected p53 antigen only in those samples in which missense p53 mutations were found. With monoclonal antibody PAb421 (which detects mutant and wild-type p53), p53 antigen was also detected in cells from F542, a bladder tumor induced by FANFT in which no p53 mutations were found. Northern blot hybridization analysis showed that p53 transcripts were elevated twofold to threefold in several cases, including F542, suggesting that constitutive overexpression of wild-type p53 may occur in some bladder neoplasias. These data support the view that p53 may be involved in multiple rate-limiting steps in neoplastic transformation and may be a continuing target during bladder carcinogenesis. The data also contribute to evidence that certain chemical carcinogens may directly alter p53 genes during tumorigenesis.

Animals↗