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Biomedical subjects

L Füzesi

Publications and source records attributed to L Füzesi.

At least 55 records · Page 3Linked to original sources

Pancreatoblastoma: ultrastructural and image DNA cytometric analysis.

BACKGROUND: Since the first description of a pancreatoblastoma as a malignant pancreatic tumour of childhood in 1957, approximately 60 cases have been reported. We present the symptoms, pathology, and therapy of this rare tumour in a 17-year-old girl. CASE REPORT: The patient initially presented with upper gastro-intestinal bleeding. During laparotomy a 16-cm (diameter) tumour was recognized in the pancreatic tail. Open biopsy and radical resection, followed by histological and immunohistochemical examinations, confirmed the diagnosis of a pancreatoblastoma. The results of single-cell DNA cytometry underlined the low DNA grade of malignancy of the primary tumour. In spite of adjuvant chemotherapy with cisplatin and adriamycin, the patient returned 22 months later with many hepatic and peritoneal metastases measuring up to 5 cm in diameter. Peritoneal tumour debulking and an extended hemihepatectomy were performed as a palliative treatment. Unfortunately, the patient died 18 months later from further tumour progression. CONCLUSIONS: A review of the literature reveals that a pancreatoblastoma in childhood has to be considered malignant, but usually shows a favourable prognosis in contrast to pancreatic neoplasms in adult patients. The treatment of choice is radical resection. Adjuvant chemotherapy or radiotherapy should be considered because of the metastatic potential of the tumour.

Adolescent↗

p53 expression in Wilms' tumor: a possible role as prognostic factor.

Although a correlation between anaplasia and mutations of the p53 tumor suppressor gene has been found in Wilms' tumor (WT) a prognostic significance of p53 in WT remains largely unresolved. The goal of this study was to obtain a better understanding of the role of p53 expression in WT. Immunohistochemical analysis was performed on formalin-fixed paraffin-embedded tumor tissues from 21 patients treated in our clinic between 1984 and 1996. Eight patients presented with stage I, six with stage II, two with stage III, four with stage IV and one patient with stage V disease. According to the presence of anaplasia, four cases were categorized as of unfavorable histology based on the criteria of the National Wilms' Tumor Study Group. Seven out of 21 WTs were positive for p53. One out of the eight patients with stage I and one out of the six patients with stage II disease scored positive for p53 as were 2/2 patients with stage III and 3/4 patients with stage IV disease. Four tumors scored positive for anaplasia (one stage I, one stage II and two stage IV disease) and all four belonged to the p53 positive group. Three of these patients died of progressive disease. Immunopositivity in general was focal in the blastemal and epithelial parts of the tumors, with differences in intensity of staining ranging from moderate to strong. Positivity in the stromal components was restricted to single cells. Statistical analysis revealed significant correlations of p53 expression to anaplasia and to survival, respectively. The association of p53 expression to tumor stage was of borderline significance. To support immunohistochemistry, we performed PCR/SSCP and DNA sequence analyses on two cases, one whose immunopositivity suggested a mutated p53, and another case which was immunonegative. A CGG --> TGG base change in codon 282 of exon 8 was found in the immunopositive tumor. In conclusion, p53 may be of prognostic relevance for poor outcome being present in close association with unfavorable histology of WTs.

Biomarkers, Tumor↗

Genomic structure and in vivo expression of the human organic anion transporter 1 (hOAT1) gene.

The human organic anion transporter 1 (hOAT1) plays a key role in the secretion of an array of potentially toxic organic anions including many clinically important drugs. Here we report on the genomic cloning of hOAT1. A human genomic library was used for screening of a PAC (P1 artificial chromosome) clone applying PCR techniques. Sequencing of several restriction subclones and of a PCR-generated clone revealed that the hOAT1 gene spans 8.2 kb and is composed of 10 exons divided by 9 introns. RT-PCR studies in a human kidney specimen led to the detection of two new splice variants, hOAT1-3 and hOAT1-4, showing a 132-bp in-frame deletion. Using fluorescence in situ hybridization (FISH) we mapped the hOAT1 gene as a single signal to chromosome 11q13.1-q13.2. Additionally, 600 bp of the 5' flanking region was analyzed, illustrating the probable transcription start site at nt -280, a NF-kappaB-site at nt -397 and several putative transcription factor binding sites.

Anion Transport Proteins↗

Clonal chromosome abnormalities in enchondromas and chondrosarcomas.

We report cytogenetic findings in short-term cell cultures from five enchondromas and four chondrosarcomas. Clonal chromosome aberrations were found in one case of enchondroma, and in all cases of chondrosarcoma. The only enchondroma with nonrandom abnormalities had a reciprocal t(8;17)(q23;p13), and monosomies 9, 19, and/or 22. In contrast to the few karyotypic findings in one of five enchondromas, the four chondrosarcomas were commonly characterized by cytogenetic heterogeneity, with a tendency for increasing karyotypic complexity in higher grade tumors. Two cases, one grade III and one metastasizing grade II chondrosarcoma, revealed hypodiploid stem- and sidelines with loss of chromosomes 6, 10, 13, 14, and 22, as common chromosomal abnormalities, suggesting a distinct karyotypic pattern in a subset of biologically aggressive chondrosarcomas.

Adolescent↗

Cytogenetic and DNA-fingerprint characterization of choriocarcinoma cell lines and a trophoblast/choriocarcinoma cell hybrid.

We report the successful fusion of human choriocarcinoma cells with normal human trophoblast cells to a choriocarcinoma/trophoblast hybrid. The hybrid cells ACH1P were derived from fusion of primary male trophoblast cells with the HGPRT-defective choriocarcinoma cell line AC1-1. The karyotypes of the parental choriocarcinoma cell line JEG-3, its HGPRT-defective mutant clones AC1-1, AC1-5, and AC1-9, and the choriocarcinoma/trophoblast hybrid ACH1P are presented, together with a detailed characterization of the AC1-specific chromosomal marker add(X)(q26) using conventional cytogenetic banding techniques and multiplex-fluorescence in situ hybridization (M-FISH). To our knowledge, this is the first report of a stably proliferating human cell hybrid of trophoblastic origin, providing a unique cell culture model to study trophoblast-related invasion and its underlying genetic mechanisms.

Cell Fusion↗

Interstitial fluid pressure is increased in renal cell carcinoma xenografts.

The purpose of this study was to test the hypothesis that renal cell carcinoma (RCC) exhibits an increased intratumoral interstitial fluid pressure (IT-IFP). Therefore, resected tumors from human primary (n = 23) or metastatic RCC (n = 3) were xenografted in SCID mice. The IFP of single tumor nodules (n = 65) and normal mouse tissue (n = 195) was measured by means of the "wick-in-needle" technique. Data demonstrate that the mean IT-IFP at neoplasia was 35 times greater than in normal tissue, and decreased precipitously at the tumor boundary. IT-IFP values tended to increase with the grade of malignancy of the tumor cells and tumor size. The mean IT-IFP of xenografts derived from primary RCC was twice as high as that from metastatic RCC tissue. These findings indicate a biophysical barrier to drug delivery in RCC; this may, in concert with cellular-based drug resistance mechanisms, be an additional explanation for resistance of the tumor to certain blood-borne anticancer therapies.

Animals↗

[Undifferentiated small-cell hepatoblastoma].

Undifferentiated small-cell hepatoblastoma (HB) is a rare malignant tumor of childhood. The cell of origin is supposed to be a pluripotential, probably entodermal, stem-cell. Differential diagnosis of this type of HB is difficult among the group of small round and blue cell malignant tumors of children. The immunohistochemically determined coexpression of cytokeratin 8, 18, and 19 and of vimentin and actin, regularly in the absence of alpha-fetoprotein expression may be diagnostically helpful. We present the case of an undifferentiated small-cell HB of a 15-month-old girl with agenesis of the right kidney. As morphological peculiarity the tumor presented disseminated histiocytic giant cells.

Actins↗

Clinical relevance of immunohistochemical expression of p53-targeted gene products mdm-2, p21 and bcl-2 in breast carcinoma.

The present study was designed to investigate the clinical/prognostic relevance of immunohistochemical expression of p53-targeted genes mdm-2, p21WAF1 and bcl-2 alone and in combination with p53 for the indirect assessment of p53 gene status in breast cancer. 141 archival breast carcinomas were immunostained, and the putative mutational status of the p53 gene was defined in 21 of them, as a control for immunohistochemistry, using the polymerase chain reaction single-strand conformational polymorphism (PCR-SSCP) analysis. Genetic changes of p53 correlated significantly with p53 protein overexpression (p = 0.01) but did not do so with any of the related molecules. Immunohistochemical p53 status was directly correlated with mdm-2 (p = 0.0001), p21 (p = 0.0004) and inversely with bcl-2 (p = 0.005) expression. bcl-2 proved to be an independent marker of prognosis, p53 only in the group of node-positive carcinomas, whereas bcl-2-/p53+ tumours revealed the worst prognosis. Mdm-2 and p21 expression was of prognostic significance neither alone nor in combination. We conclude that the detection of down-stream regulators of p53 does not increase the efficacy of immunohistochemistry in assessing the functional status of p53 in breast cancer; however, their combined analysis may help to select subgroups of patients at the extremes of risk for recurrence, or those with greater chances for survival.

Adult↗

Preoperative B-mode ultrasound plaque appearance compared with carotid endarterectomy specimen histology.

In carotid artery stenosis both the degree of the lesion and its plaque morphology are thought to be associated with the carrier's thromboembolic risk. In this study we evaluated the diagnostic preciseness of non-invasively B-mode ultrasound in predicting the histopathological plaque structure. We examined 44 patients with > 50% ICA stenosis by B-mode within 6 weeks prior to carotid endarterectomy. At the affected bifurcations, up to 10 different regions of interest (ROI) per artery were investigated. Plaque appearance was classified according to 6 subtypes considering different ultrasonic plaque features. Postoperatively, plaque specimens were examined histopathologically for their relative content of calcification, fibrous tissue and different soft tissue. B-mode ultrasound was compared with histopathological features in ROI. A total of 265 regions of interest were evaluated. In mainly echolucent types of plaques, atheromatous debris was most frequently seen, whereas fibrosis was rare. Homogeneous echolucent plaques showed a high proportion of cholesterol and/or recent haemorrhage. Thrombosis at the plaque surface was often seen in "completely echolucent" plaque type (each P<0.001). Carotid B-mode ultrasonography is able to predict the histopathological components and the texture of carotid plaques.

Adipose Tissue↗

[The radial scar in contrast media-enhanced MR mammography].

INTRODUCTION: In patients with the mammographic findings of a radial scar, contrast enhanced (CE) MR mammography was evaluated in a retrospective study. MATERIAL AND METHODS: In 24 women with radial opacities and black star configurations, CE MR mammography was performed. Examinations were done on a 1.5 T system using bilateral superficial coil (2D technique, T1-weighted FLASH-sequence, TR 336 ms, TE 5 ms, FA 90 degrees). Findings in mammography and MR mammography were compared with the histological results. RESULTS: 15 radial scars (including 4 with additional ADH) and 9 carcinomas (6 in coexistence with a radial scar) presenting with a diameter of 3 mm to 13 mm were evaluated. There was no evidence of malignancy in MRI in 12 of 15 radial scars. In MR mammography 6 of the carcinomas fulfilled the criteria for malignant tumors. There were 3 borderline cases (scored 3 points) corresponding histologically to 1 radial scar, and to 2 carcinomas. Within the results found in MRI there were 2 false positives and 1 false negative. CONCLUSION: CE MR mammography is superior to other imaging modalities in the differentiation between radial scars and carcinomas. However, lesions suggestive of radial scars have to be removed surgically.

Adult↗

[Papillary renal cell carcinoma: comparison of CT and gross morphology].

OBJECTIVE: To analyze the CT appearance of papillary renal cell tumor (pRCT) under consideration of gross pathology. MATERIAL AND METHODS: Preoperative CT-scans of 10 patients suffering from pRCT were re-evaluated by two experienced radiologists. CT appearance was correlated to gross morphology. RESULTS: On CT, 9/10 tumors were depicted as rounded, well circumscribed and sharply delineated masses. These tumors presented a hypodense central area correlating to necrosis in gross pathology. The central area of necrosis was surrounded by vital tumor tissue, presenting as a serpiginous, contrast-enhancing margin on CT. One tumor was polycyclic due to multiple tumor nodules, but sharply demarcated towards the surrounding renal tissue. CONCLUSIONS: pRCT presents a quite unique CT appearance similar to its gross pathology.

Adult↗

Papillary squamous cell carcinoma of the uterine cervix: report of three cases and a review of its classification.

Papillary squamous cell carcinoma (SCC) of the uterine cervix has been defined as a malignant squamous cell lesion characterized by a papillary architecture with fibrovascular cores and moderate to severe dysplasia devoid of frank keratinization and koilocytic change. Papillary SCC should be histopathologically delineated from other rare variants of SCC with papillary features including verrucous and condylomatous carcinoma and the recently recognized (squamo-)transitional cell carcinoma of the uterine cervix. We report three cases of papillary SCC (FIGO stages IB, IV, and IVB) in postmenopausal women. Each tumor tested was positive for human papillomavirus (HPV) 16 and negative for HPV 6, 11 and 18 by general primer mediated polymerase chain reaction and subsequent enzyme-linked immunosorbent assay (PCR-ELISA). These findings 1) support the hypothesis that papillary SCCs (unlike verrucous carcinoma) are similar with regard to risk factors to (squamo-)transitional and condylomatous carcinoma; 2) suggest that HPV may play an etiologic role in at least some of these tumors; and 3) suggest that papillary SCC is the only subtype among squamous/(squamo-)transitional carcinomas that is associated with high-risk HPV infection in the absence of HPV-related histopathologic alterations.

Aged↗

Prognostic significance of p53/bcl-2 co-expression in patients with laryngeal squamous cell carcinoma.

OBJECTIVE: The p53, bcl-2, and bax genes are known to be involved in control of cell cycle progression and regulation of apoptotic cell death. Although they are frequently altered in laryngeal squamous cell carcinoma, their clinical relevance is not yet fully understood. In the present study, individual and combined expressions of these genes were related with patient survival as well as with proliferative and apoptotic activity. DESIGN: Retrospective study. METHODS: Paraffin-embedded tissue sections of 88 laryngeal squamous cell carcinomas that were diagnosed and treated between 1986 and 1996 were investigated for p53, bcl-2, and bax protein expression by immunohistochemistry. Apoptotic cells were visualized using the nick end labeling method. To assess proliferative activity of tumors, mitotic indices were determined. RESULTS: Age of patients, advanced disease (stages HI and IV), high mitotic activity, positive bcl-2 expression, high level of p53 expression, and p53/bcl-2 co-expression were significantly associated with shortened overall survival in univariate analysis. In multivariate analysis, only age and p53/bcl-2 co-expression had independent prognostic value. Other combinations of genes, i.e., bcl-2-to-bax and p53-to-bax ratios, were not associated with patient outcome. A significant positive correlation was found between apoptotic and mitotic activity. However, protein levels of p53, bcl-2, and bax were unrelated to proliferation and apoptosis of tumor cells. CONCLUSIONS: The co-expression of p53/bcl-2 was an independent predictor of patient outcome and had a prognostic value superior to both parameters considered separately. The rate of apoptosis mainly counterbalanced proliferative activity but appeared not to be significantly influenced by p53, bcl-2, and bax.

Apoptosis↗

Human papillomavirus genotypes in cervical cancer with different histological features.

We report the case of a 32-year-old woman having developed two cervical cancers synchronously, an adenocarcinoma and a squamous cell carcinoma. Polymerase chain reaction with the general primers GP5/GP6 and a subsequent enzyme-linked immunosorbent assay to detect human papillomaviruses (HPV) resulted in isolation of HPV 33 in the squamous cell carcinoma and HPV 18 in the adenocarcinoma. This is the first reported case of two histologically different synchronous cervical cancers with this distinct HPV expression pattern, and further confirms the association of certain 'high-risk' HPV genotypes to different histological features of carcinoma. Furthermore, the important role of microdissection for gaining tumor tissue of different areas in molecular diagnostics is supported.

Adenocarcinoma↗

Inflammatory pseudotumor of the diaphragm.

A 5-year-old-boy presented with a right pleural effusion and fever. A tumorous mass was located between the right lung and the liver. The boy underwent a right thoracotomy with excision of the tumor and the adherent parts of the right hemidiaphragm. Histology and immunohistochemistry showed an inflammatory pseudotumor of the diaphragm. This is the first reported case of an inflammatory pseudotumor in this location. A brief review of the heterogeneous theories about the pathogenesis and the different therapeutic regimens for this rare neoplastic entity are discussed.

Biopsy↗

Polyploidization and losses of chromosomes 1, 2, 6, 10, 13, and 17 in three cases of chromophobe renal cell carcinomas.

Clonal chromosome aberrations identified after short-term culture are presented for three cases of chromophobe renal cell carcinomas (RCC). All tumors revealed abnormal karyotypes with a varying proportion of polyploid tumor cells. Common numerical abnormalities were combined losses of chromosomes 1, 2, 6, 10, 13, and 17. Clonal karyotypic evolution was demonstrated in one case in which several related clones could be identified. An additional balanced translocation t(3;14)(p24;q22) observed in this case proved to be of constitutional nature by cytogenetic analysis of normal kidney cells and peripheral blood lymphocytes. These cytogenetic findings provide further evidence that chromophobe renal cell carcinomas are characterized by a highly specific combination of chromosomal losses most commonly including chromosomes 1, 2, 6, 10, 13, and 17.

Adenocarcinoma↗

Papillary renal cell carcinoma with clear cell cytomorphology and chromosomal loss of 3p.

AIMS: Cytogenetic studies on renal cell carcinomas (RCCs) have disclosed a correlation between chromosome aberrations and histomorphological features. Nevertheless, it is still controversial whether the cytomorphology of the tumour cells (clear cell, chromophilic, chromophobe) or their growth pattern (nonpapillary, papillary) is more discriminative for the combined histomorphological-cytogenetic classification of RCCs. METHODS AND RESULTS: Three RCCs with papillary growth pattern and clear cell cytomorphology were analysed by classical cytogenetics using standard G-banding techniques. Each tumour displayed clonal aberrations leading to loss of terminal 3p chromosomal segments. Monosomy 14 was also consistently found. Trisomy 17 was not observed in any of the tumours. CONCLUSIONS: This series of three RCCs consisting of clear cells with papillary architecture revealed chromosomal aberrations characteristic for the conventional (clear cell) RCC. Irrespective of the predominant papillary growth pattern, none of the cases were characterized by trisomy of chromosomes 3q, 7, 8, 12, 16, 17 and 20 and loss of Y chromosome which are widely regarded as the most consistent genetic alterations for papillary RCC. Therefore, our cytogenetic findings provide evidence that papillary clear cell RCCs should be classified according to their cytomorphology rather than their growth pattern even when papillary architecture is prominent.

Adult↗