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Biomedical subjects

W Biernat

Publications and source records attributed to W Biernat.

At least 37 records · Page 2Linked to original sources
PubMed1999

Retiform/racemiform neoplasm with features of clear cell hidradenoma.

We report a case of a 78-year-old woman with a tumor of the left cheek. The tumor was a well-circumscribed cystic/solid nodule with a racemiform and reticulated pattern of growth of its epithelial cells, and mucinous and fibrocytic stroma. The epithelial cords and strands were continuous with the apocrine lining of large cystic structures. The main bulk of the epithelial component was formed by the proliferation of clear cells. This tumor is an example of an unusual benign neoplasm with racemiform and retiform patterns having a histogenetical link with the folliculo-sebaceous-apocrine unit.

Adenoma, Sweat Gland↗
PubMed1999

Dysembryoplastic neuroepithelial tumor (DNT): an ultrastructural study of six cases.

We report six cases od DNT with a detailed ultrastructural characteristics. The patient age ranged from 7 to 16 years (mean 12), the location was temporal in three cases and frontal, temporooccipital and parietooccipital in each of one remaining cases. The predominant clinical feature in each case was history of episodes of intractable seizures. Histopathologically, the neoplasms were multinodular, each nodule was well-circumscribed and was composed of glioneuronal elements embedded in the variable amount of myxoid matrix. The oligodendroglial-like cells (OLC) predominated in the nodules with some accompanying mature neurons. The nodules were frequently surrounded by small calcifications which could be found also within the tumors. OLCs were immunoreactive for S-100 protein and neurons had the expression of synaptophysin and neurofilament proteins. Ultrastructurally, each tumor consisted of three major elements: neoplastic cells (OLC), elongated processes forming neuropil-like structure and expanded "mucoid" extracellular space: the latter gave an impression of cellular elements floating within it. Neoplastic cells had round, oval or elongated nuclei, no discernible nucleoli and a relatively narrow rim of the cytoplasm. Some nuclei were irregular and invaginated and pseudoinclusions were observed; a part of cytoplasm sequestered within pseudoinclusions often appeared degenerated with large blabs and electron-lucent vesicles, some of these contained in turn semicircular profiles of unknown significance. The second element consisted of innumerable cellular processes. Some of these were elongated and formed stacks connected by symmetrical symmetric or asymmetric adhesive plaque junctions. The others had shorter "neck" containing microtubules, these extended into bullous extensions. Dense-cored vesicles were occasionally observed, in both cytoplasm of neoplastic cells and within processes. In one cell, cross-sectioned annulate lamellae were found. In cytoplasm of a few cells, unusual inclusions reminiscent ribosome-lamellae complexes were observed. These were cylindrical resembling "laboratory tubes" with a cone-like endings. At higher power, walls of the "tubes" resolved into layered structures composed of several laminae; between laminae, ribosome-like structures were visible.

Adolescent↗
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

p53 mutations in sweat gland carcinomas.

Sweat gland carcinomas are rare skin tumours and little is known about their etiology and molecular basis. In this study, we analyzed p53 mutations in 16 sweat gland carcinomas with different histologic types, including 2 spiradenocarcinomas, 1 composed adnexal carcinoma, 5 porocarcinomas, 2 eccrine hidradenocarcinomas, 2 syringocystadenocarcinomas, 1 sclerosing sweat gland carcinoma, 1 adenoid cystic carcinoma, 1 cylindrocarcinoma and 1 apocrine adenocarcinoma. Single-stranded conformation polymorphism (SSCP) analyses followed by direct DNA sequencing revealed that 5 carcinomas (31%) contained a p53 mutation, 4 of which were G:C-->A:T transition mutations and 1 of which was a deletion. Three G:C-->A:T mutations were located at dipyrimidine sequences on the antisense strand (2 spiradenocarcinomas, 1 eccrine hidradenocarcinoma), suggesting that UV light may play a role in the development of sweat gland carcinomas. In 2 spiradenocarcinomas, p53 mutations were present in the carcinoma but not in the adenoma portions, suggesting that p53 mutations may be associated with malignant progression in these rare adnexal tumours.

Adenocarcinoma↗
PubMed1998

PTEN (MMAC1) mutations are frequent in primary glioblastomas (de novo) but not in secondary glioblastomas.

Loss of heterozygosity (LOH) on chromosome 10 is the most frequent genetic alteration associated with the evolution of malignant astrocytic tumors and it may involve several loci. The tumor suppressor gene PTEN (MMAC1) on chromosome 10q23 is mutated in approximately 30% of glioblastomas (WHO Grade IV). In this study, we assessed the frequency of PTEN mutations in primary glioblastomas, which developed clinically de novo, and in secondary glioblastomas, which evolved from low-grade (WHO Grade II) or anaplastic astrocytomas (WHO Grade III). Nine of 28 (32%) primary glioblastomas contained a PTEN mutation and an additional case showed a homozygous PTEN deletion. This indicates that after overexpression/amplification of the EGF receptor, loss of PTEN function is the most common alteration in primary glioblastomas. In this series, 5 of 28 (18%) primary glioblastomas showed both a PTEN mutation and EGFR amplification. In contrast, only 1 of 25 (4%) secondary glioblastomas contained a PTEN mutation, and none of them showed a homozygous PTEN deletion. The secondary glioblastoma with a PTEN mutation developed from an anaplastic astrocytoma that already carried the mutation. The observation that secondary glioblastomas have a p53 mutation as a genetic hallmark but rarely contain a PTEN mutation supports the concept that primary and secondary glioblastomas develop differently on a genetic level.

Adult↗
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

Desmoplastic cerebral astrocytoma of infancy: a case report.

We report a case of desmoplastic cerebral astrocytoma of infancy (DCAI), in a 7-month-old boy. DCAI belongs to a group of recently described central nervous system (CNS) tumors, which also includes desmoplastic infantile ganglioglioma (DIG), pleomorphic xanthoastrocytoma (PXA) and dysembryoplastic neuroepithelial tumor (DNT), all characterized by relatively favorable prognosis and occurring mostly in children and young adults. DCAI is a rare neoplasm arising in the cerebral hemispheres within the first two years of life, and histologically is characterized by dense fibrous desmoplasia. In our case, CT scan presents a massive partially cystic tumor of the left cerebral hemisphere with an enlargement of the ventricular system. Histologically, the tumor was composed of cells arranged in fascicles and whorls forming storiform pattern. Immunohistochemical stainings for glial fibrillary acidic protein proved glial histogenesis of this tumor, while no cells were unequivocally immunopositive for neuron specific enolase, neurofilament proteins and synaptophysin what excludes a diagnosis of DIG--a similar entity but containing also a neuronal elements. Our studies, comprising a complete clinical, radiological, histopathological and immunohistochemical data, correspond to a cases of DCAI published before and it is the first one described in Poland.

Astrocytoma↗
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

Alterations of cell cycle regulatory genes in primary (de novo) and secondary glioblastomas.

Primary glioblastomas develop rapidly de novo through a genetic pathway characterized by amplification/overexpression of EGFR and of MDM2 genes. Secondary glioblastomas develop more slowly through progression from low grade or anaplastic astrocytoma and show a high incidence of a p53 mutation. In the present study, primary and secondary glioblastomas were analyzed for p16 deletions and CDK4 amplification by differential PCR and for loss of expression of the retinoblastoma (RB) gene by immunohistochemistry. Except for one case, alterations in the structure or expression of p16, CDK4 and RB were mutually exclusive. The overall incidence of aberrant expression of these genes coding for components of the cell-cycling-regulatory system was similar in primary (14/28; 50%) and secondary glioblastomas (9/23; 39%). However, p16 deletions were significantly more frequent in the former (10/28; 36%) than in the latter (1/23, 4%; P = 0.0075), suggesting that this alteration constitutes an additional genetic hallmark of the primary (de novo) glioblastoma.

Adult↗
PubMed1997

Amplification and overexpression of MDM2 in primary (de novo) glioblastomas.

Glioblastoma multiforme (WHO Grade IV), the most malignant neoplasm of the human nervous system, develops rapidly de novo (primary glioblastoma) or through progression from low-grade or anaplastic astrocytoma (secondary glioblastoma). We recently reported that mutations of the p53 gene are present in more than two-thirds of secondary glioblastomas but rarely occur in primary glioblastomas, suggesting the presence of different genetic pathways (Watanabe et al, Brain Pathol 1996:6:217-24). In the present study, primary and secondary glioblastomas were screened by immunohistochemistry for MDM2 overexpression and by differential PCR for gene amplification. Tumor cells immunoreactive to MDM2 were found in 15 of 29 primary glioblastomas (52%), but in only 3 of 27 secondary glioblastomas (11%; P=0.0015). MDM2 amplification occurred in 2 primary (7%) glioblastomas but in none of the secondary glioblastomas. Only one out of 15 primary glioblastomas overexpressing MDM2 contained a p53 mutation. These results suggest that MDM2 overexpression with or without gene amplification constitutes a molecular mechanism of escape from p53-regulated growth control, operative in the evolution of primary glioblastomas that typically lack p53 mutations.

Adult↗
PubMed1997

Reduced expression of the P2 form of the gap junction protein connexin43 in malignant meningiomas.

Neoplastic transformation is often associated with aberrant gap junctional intercellular communication. We assessed mutations and expression of the connexin43 (Cx43) gene in 49 intracranial meningiomas. SSCP analyses followed by direct DNA sequencing showed GCG-->GTG (Ala-->Val) transition mutation in codon 253 of the cytoplasmic carboxyl terminal of the Cx43 gene in 1 of 31 (3%) benign meningiomas and 1 of 14 (7%) anaplastic meningiomas. The same base change was present in normal tissue from these patients and also in 4 of 80 (5%) DNA samples extracted from lymphocytes of healthy Europeans, suggesting that this constitutes a newly identified Cx43 polymorphism. Western blot analyses showed expression of phosphorylated P1 (45 kD) and P2 (47 kD) Cx43 as well as the unphosphorylated form (42 kD) in 11 of 14 (79%) benign meningiomas. In contrast, the P2 form was not detectable in the majority (7 of 9; 78%) of atypical and anaplastic meningiomas. Since the presence of the P2 form is often associated with optimal function of the Cx43, these results suggest that loss or impaired gap junctional cell to cell communication may be associated with meningiomas displaying more rapid growth and a less favorable prognosis.

Adult↗
PubMed1997

Ultrastructural study of subependymal giant cell astrocytoma: unusual paracrystalloid inclusions in tumour cells.

Subependymal giant cell astrocytoma (SEGA) is a tumour with a broad range of morphological, immunohistochemical and ultrastructural neoplastic cellular features. We report here the presence of this tumor in two 7-year-old-boys presented with a lateral intraventricular mass. Further clinical investigation confirmed the diagnosis of tuberous sclerosis. Ultrastructural and immunohistochemical investigation revealed that glial differentiation was more pronounced in these cases. Interestingly, tumour cells containing unusual paracrystalline inclusions, infrequently described in SEGA, were identified ultrastructurally. These inclusions are probably not related to other cellular organelles.

Brain Neoplasms↗
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↗
PubMed1997

Incidence and timing of p53 mutations during astrocytoma progression in patients with multiple biopsies.

Mutations of the p53 tumor suppressor gene are a genetic hallmark of human astrocytic neoplasms, but their predictive role in glioma progression is still poorly understood. We analyzed 144 biopsies from 67 patients with recurrent astrocytoma by single-strand conformation polymorphism and direct DNA sequencing. We found that 46 of 67 patients (69%) had a p53 mutation in at least one biopsy. In 41 of these (89%), the mutation was already present in the first biopsy, indicating that p53 mutations are early events in the evolution of diffuse astrocytomas. Double mutations of the p53 gene were observed in three tumors and also present from the first biopsy. Of 28 low-grade astrocytomas with a p53 mutation, 7 (25%) showed loss of the normal allele in the first biopsy. The allele status remained the same in 95% of the cases, irrespective of whether the recurrent lesion had the same or a higher grade of malignancy. Progression of low-grade astrocytomas to anaplastic astrocytoma or glioblastoma occurred at a similar frequency in lesions with (79%) and without (63%) p53 mutations (P = 0.32), indicating that this genetic alteration is associated with tumor recurrence but not predictive of progression to a more malignant phenotype. However, the time interval until progression was shorter in patients with low-grade astrocytomas carrying a p53 mutation (P = 0.055).

Adult↗
PubMed1996

Proliferating tricholemmal cyst: a possible pitfall in cytological diagnosis.

We report a case of proliferating tricholemmal cyst, which made difficulties in the cytological analysis of the fine-needle biopsy aspirates. This rare dermatopathologic entity is a possible diagnostic pitfall due to its close cytological resemblance to squamous cell carcinoma-the abundance of material, with predominance of squamoid cells, which form concentric structures (so-called squamous eddies), that simulate keratin pearls of well-differentiated squamous cell carcinoma. However, careful and strict application of the cytological criteria prevents overdiagnosis; the small squamoid cells that predominate in the smears occur mainly in clusters and sheets, they do not show prominent atypia, and the squamous eddies may not undergo complete keratinization.

Adenoma↗
PubMed1996

Proliferating cell nuclear antigen (PCNA) and Ki-67 immunopositivity in human astrocytic tumours.

To compare the Ki-67 and Proliferating Cell Nuclear Antigen (PCNA), markers of cell proliferation, paraffin embedded surgical specimens from 56 human astrocytic tumours (8 pilocytic tumours, grade I; 9 low (II) grade and 9 anaplastic (grade III) astrocytomas and 30 glioblastomas, grade IV) were immunolabelled with the anti-PCNA (PC 10, DAKO) and anti-Ki-67 (DAKO) antibodies. For the latter immunostaining the microwave oven processing was performed. The Ki-67 and PCNA labelling indices (LIs) were statistically compared. For the majority of cases, PCNA LI was higher than that obtained with anti-Ki-67 antibody and the intensity of staining for PCNA was more variable. The statistically significant difference of the percentage of PCNA LIs was found only between low grade (I and II) and high grade (III and IV) tumours, while Ki-67 LIs discriminates each group of glial tumours; thus this latter marker is more sensitive and specific.

Astrocytoma↗