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A Bankfalvi

Publications and source records attributed to A Bankfalvi.

18 recordsLinked to original sources

Endosonographic and histopathological staging of extrahepatic bile duct cancer: time to leave the present TNM-classification?

OBJECTIVES: The discrepancy between high rates of sensitivity, specificity, and accuracy for intraductal ultrasonography (IDUS) in extrahepatic bile duct carcinoma and the failure to depict different wall layers as defined by the TNM classification have not yet been elucidated sufficiently. METHODS: In a prospective study, endosonographic images were correlated with histomorphology including immunohistochemistry. Using IDUS, we examined fresh resection specimens of patients who had undergone pancreato-duodenectomy. For histological analysis, the formalin-fixed and paraffin-embedded specimens were stained by hematoxylin-eosin, elastica-van-Gieson, and immunohistochemically by smooth muscle-actin. To confirm our hypothesis, further cases from the archives were analyzed histopathologically and immunohistochemically. RESULTS: The various wall layers of the extrahepatic bile duct as described by the International Union Against Cancer are neither histomorphologically nor immunohistochemically consistently demonstrable. Especially, a clear differentiation between tumor invasion beyond the wall of the bile duct (T2) and invasion of the pancreas (T3) by histopathological means is often not possible. Endosonographic images using high-resolution miniprobes similarly confirm the difficulty in imaging various layers in the bile duct wall. CONCLUSIONS: Most adaptations made by the sixth edition of the TNM classification accommodate to the endosonographic and most of the histopathological findings as demonstrated in our study. In contrast to the new edition, however, our findings suggest to combine T2- and T3-staged tumors into one single class leading to clarification, and improved reproducibility of histopathological staging.

Aged↗

Prognostic value of graph theory-based tissue architecture analysis in carcinomas of the tongue.

Several studies on oral squamous cell carcinomas (OSCC) suggest that the clinical value of traditional histologic grading is limited both by poor reproducibility and by low prognostic impact. However, the prognostic potential of a strictly quantitative and highly reproducible assessment of the tissue architecture in OSCC has not been evaluated. Using image analysis, in 193 cases of T1-2 (Stage I-II) OSCC we retrospectively investigated the prognostic impact of two graph theory-derived structural features: the average Delaunay Edge Length (DEL_av) and the average homogeneity of the Ulam Tree (ELH_av). Both structural features were derived from subgraphs of the Voronoi Diagram. The geometric centers of the cell nuclei were computed, generating a two-dimensional swarm of point-like seeds from which graphs could be constructed. The impact on survival of the computed values of ELH_av and DEL_av was estimated by the method of Kaplan and Meier, with relapse-free survival and overall survival as end-points. The prognostic values of DEL_av and ELH_av as computed for the invasive front, the superficial part of the carcinoma, the total carcinoma, and the normal-appearing oral mucosa were compared. For DEL_av, significant prognostic information was found in the invasive front (p < 0.001). No significant prognostic information was found in superficial part of the carcinoma (p = 0.34), in the carcinoma as a whole (p = 0.35), or in the normal-appearing mucosa (p = 0.27). For ELH_av, significant prognostic information was found in the invasive front (p = 0.01) and, surprisingly, in putatively normal mucosa (p = 0.03). No significant prognostic information was found in superficial parts of the carcinoma (p = 0.34) or in the total carcinoma (p = 0.11). In conclusion, strictly quantitative assessment of tissue architecture in the invasive front of OSCC yields highly prognostic information.

Aged↗

[Tumor suppressor gene p53. Theoretical principles and their significance for pathology].

Mutations of the p53 tumor-suppressor gene are the most common genetic alterations in human cancer, found in approximately 50% of all tumors. The importance of p53 in human cancer attracts attention in molecular studies dealing with the pathogenesis, diagnosis and prognosis in tumor pathology. This review summarizes the current understanding of p53 both on the genetic and protein level. Frequency and spectrum of somatic p53 mutations in the carcinogenesis of breast cancer, colorectal cancer, gastric cancer, hepatocellular carcinoma, squamous-cell carcinoma of the skin and malignant melanoma are discussed including our own investigations and studies published in the literature.

Animals↗

Primary non-Hodgkin lymphomas of the CNS-proliferation, oncoproteins and Epstein-Barr-virus.

Primary cerebral lymphomas (PCL's) are rare tumors which, however, occur with increasing frequency. The present study investigated 55 PCL's of B-cell type, 36 in immunocompetent and 19 in AIDS-patients and 6 cases of intravascular lymphomatosis. In immunocompetent patients, proliferative indices as evaluated by PC10 and MIB1 reflected the histologic grade. Low grade tumors had a mean PCNA and MIB-1 count of 19 and 18.8 (SD 14.7 and 13.2), respectively, and high grade neoplasias showed counts of 56.7 and 47.1 (SD 19 and 17.4), respectively. No correlation of both indices with patient survival was found. 21 cases (58.3%) displayed p53-positivity of varying degree and 19 cases (52.7%) harbored bcl-2 positive neoplastic cells. Immunocompetent cases were always negative for Epstein-Barr virus RNA and lmp-1-protein. In AIDS-cases, 13 cases (68.4%) showed up lmp-1 positivity and 15 cases (78.9%) had EBER-RNA. bcl-2 positive cells were detected in 5 cases (26.3%) and all cases were p53-negative. These results are in keeping with a role of EBV in the pathogenesis of primary cerebral lymphomas in AIDS-, but not in immunocompetent patients. None of the cases with intravascular lymphomatosis showed an expression of bcl-2 or p53 oncoproteins or lmp-1 and none had EBER-RNA.

Adult↗

MIB1 in colorectal carcinomas: its evaluation by three different methods reveals lack of prognostic significance.

Immunohistochemically detected MIB1 has been determined in a series of 106 colorectal carcinomas with three different evaluation methods (semiquantitative estimation, evaluation by image analysis, and cell count). Although the semiquantitative estimation correlated significantly with results obtained by image analysis (R = 0.8), both methods were only poorly associated with MIB1 counts (R = 0.5). Additionally, all three methods revealed no statistical correlation of MIB1 with the clinical outcome of the respective patients. Our results indicate a pronounced heterogeneity of MIB1 in colorectal adenocarcinoma, thus leading, irrespectively of the evaluation method used, to non-representative results with lack of clinical relevance.

Adenocarcinoma↗

Immunohistochemical detection of p53 protein in archival tissues from squamous cell carcinomas of the oral cavity using wet autoclave antigen retrieval.

Using a panel of four anti-p53 antibodies (CM-1, PAb 1801, DO7, and PAb 240), the phenotypic characteristics of p53 protein overexpression were investigated in 22 routinely formalin-fixed and paraffin-embedded squamous cell carcinomas of the oral cavity. Conventional immunohistochemical staining without pretreatment for antigen retrieval was compared with wet autoclaving (AC) and microwave irradiation (MW). Applying AC or MW, p53 immunoreactivity was demonstrated in 9/22 cases with PAb 1801 and DO7 antibodies and in 8/22 cases with the CM-1 antibody. Immunostaining with the PAb 240 antibody after AC pretreatment showed p53 positivity in 8/22 tumours, but in only 4/22 following MW pretreatment. Immunostaining without pretreatment revealed only 2/22 p53-positive cases using CM-1, 4/22 with PAb 1801, and 3/22 with DO7. Without pretreatment, the PAb 240 antibody was consistently negative. Wet autoclave pretreatment was significantly superior for all the antibodies used in this study when compared with conventional immunohistochemistry without pretreatment (P < 0.005). It yielded better results than microwave irradiation for antigen unmasking in relation to the PAB 240 antibody (P < 0.05). Wet autoclave pretreatment is recommended as a reliable and highly reproducible method for p53 antigen retrieval in routinely processed archival material. The advantages over microwave pretreatment include simple handling and good preservation of morphology.

Carcinoma, Squamous Cell↗

Wet autoclave pretreatment for immunohistochemical demonstration of oestrogen receptors in routinely processed breast carcinoma tissue.

The immunohistochemical demonstration of oestrogen receptor (OR) was performed on 32 randomly selected and routinely processed breast carcinomas after wet autoclave pretreatment of sections. The autoclave method was compared to the OR status found on frozen sections as well as to alternative pretreatment methods such as enzymatic predigestion and microwave irradiation. Using four different monoclonal antibody clones (H222, LH1, CC4-5, 1D5.26), the OR status was evaluated for each of the various pretreatment methods applied. All cases with a high OR content on frozen sections (n = 11) also showed a high OR status on wet autoclave-pretreated paraffin tissues using antibody clones 1D5.26 and CC4-5; in cases with low OR content on frozen sections, no false-negative cases were recorded using only the antibody 1D5.26 neither after wet autoclave nor microwave pretreatment. In addition, with this antibody, OR was detectable after autoclave pretreatment in two cases which were considered to be OR-negative even on frozen sections. When the primary antibody was omitted, no false-positive cases were observed after wet autoclave pretreatment. Thus, in our hands, wet autoclave pretreatment, in combination with the antibody 1D5.26, offers a highly sensitive method for the immunohistochemical demonstration of OR in routinely formalin-fixed, paraffin-embedded sections of breast carcinomas.

Antibodies, Monoclonal↗

Immunohistochemically detectable p53 and mdm-2 oncoprotein expression in colorectal carcinoma: prognostic significance.

Aims-To investigate the correlation between the expression of the p53 and mdm-2 oncoproteins and to assess their prognostic value in colorectal cancer.Methods-Using a polyclonal (CM1) and a monoclonal antibody directed against p53 and mdm-2, respectively, these oncoproteins were stained immunohistochemically in 109 colorectal adenocarcinomas.Results-p53 was detected in less than 10% of tumour cells in 11 of 109 adenocarcinomas, in 10-50% of tumour cells, in 17 of 109 adenocarcinomas, and in more than 50% of tumour cells in 32 of 109 adenocarcinomas. Expression of mdm-2 was detected in 22 of 109 (20%) cases investigated, of which 19 showed concomitant p53 expression. In most cases mdm-2 immunoreactivity was strongly associated with a small proportion of p53 positive tumour cells. Both p53 and mdm-2 expression lacked statistical significance when correlated with common staging and grading parameters.Conclusions-Detection of p53 and mdm-2 oncoprotein expression, detected using immunohistochemistry, is of no prognostic value in colorectal cancer. However, the close correlation between mdm-2 immunoreactivity and the proportion of p53 positive cells provides further evidence that the mdm-2 gene product interacts with p53 protein.

Journal Article↗

Wet autoclave pretreatment for antigen retrieval in diagnostic immunohistochemistry.

Interest has recently been shown in adapting the microwave oven heating technique for antigen retrieval to routine diagnostic immunocytochemical practice. Although it has proved effective as a specialist method for individual antigen localization in many laboratories, it has certain drawbacks which have hampered its wider routine application. These include the need to monitor the sections during the microwave treatment to prevent damage or drying, the limited number of sections that can be accommodated in the microwave oven, and the inevitable alteration in nuclear morphology induced by the microwaves. In order to obviate these difficulties, we have modified the wet autoclave method of Shin et al. (Lab Invest 1991; 64: 693-702) as a routine technique for retrieval of a variety of cell surface, cytoplasmic, and nuclear antigens in formalin-fixed and paraffin-embedded tissue. The technique produces even enhancement of several refractory antigens in anatomically different sites and has the potential to handle reliably up to 200 sections at a time without significant damage to the section or to nuclear morphology.

Antigens↗

[In situ hybridization. Theoretical principles and practical applications].

In situ hybridisation is a sensitive and reliable technique for the demonstration of DNA- or mRNA-sequences on histological tissue preparations. This review deals with the theoretical background as well as the benefits and limitations of the method; additionally the value of in situ hybridisation as a tool in routine diagnostic pathology is briefly described.

Base Sequence↗

[A standardized AgNOR stain method for formalin fixed and paraffin embedded material].

Visualization of proteins associated with nucleolar organizer regions proteins (AgNORs) on formalin-fixed and paraffin-embedded archival tissues is substantially improved after application of wet autoclave pretreatment. Silver staining results are comparable to those obtained on tissues processed in alcohol based fixatives, illustrating AgNORs as substructures of the nucleoli without any staining artefacts. A highly reproducible staining quality was achieved irrespective of tissue origin or duration of formalin fixation. As a result of this novel and simple method, the grounds have been prepared for standardized AgNOR quantification on archival material.

Fixatives↗

[Moist autoclaving. A simplified method for antigen unmasking].

Wet autoclaving is a simple, reliable and time-effective method for antigen retrieval in routinely processed archival material. Both routine diagnostic (e.g., oestrogen and progesterone receptors, cytoskeletal proteins) and research antibodies (e.g. various p53 antibodies, mdm-2, bcl-2, MIB-1) are reported to demonstrate its application. We autoclaving may allow successful application of antibodies in paraffin-embedded tissues designed for use on frozen sections. The technique has the potential to reliably handle up to 200 sections at a time, without evidence of any significant damage to the sections or nuclear morphology.

Antigens, Neoplasm↗

Wet autoclave pretreatment improves the visualization of silver-stained nucleolar organizer-region-associated proteins in routinely formalin-fixed and paraffin-embedded tissues.

This study describes the effect of wet autoclave pretreatment of routinely formalin-fixed and paraffin-embedded tissues on silver-stained nucleolar organizer-region-associated proteins (AgNORs) staining. The treatment of sections at superheated steam temperature (120 degrees C) before silver incubation leads to a significantly better discrimination of single-interphase AgNORs. Counting "black dots" both by eye and by means of a computer-aided image-analyzing system revealed considerably higher AgNOR mean numbers per nucleus in all pretreated cases when compared with the respective untreated controls. However, mean AgNOR numbers increased after autoclave pretreatment in a nonlinear manner (pairwise comparison by means of Spearman's Rank correlation coefficient: rho = 0.5), whereas measurement of the AgNOR area was less influenced by autoclave pretreatment (rho = 0.8). It is concluded that wet autoclave pretreatment of routinely formalin-fixed and paraffin-embedded archival material should be applied before AgNOR staining, particularly when quantitation of AgNORs involves counting procedures.

Adenocarcinoma↗

Proteoglycan-targeted antibodies as markers on non-Hodgkin lymphoma xenografts.

A family of mono- and polyclonal antibodies raised against proteoglycans or their "subcomponents" served as novel markers to characterize the phenotypes of three non-Hodgkin lymphoma xenograft lines (HT 58 lymphoblastic, HT 117 centroblastic, HT 130 centrocytic) together with normal, human peripheral blood B lymphocytes. These xenografted NHL lines, maintained by serial transplantations on artificially immunosuppressed mice, expressed very similar B-cell-related antigens and differences on the cell surface (HT 58 greater than HT 117 greater than HT 130 greater than B cells) when they were exposed to monoclonal antibodies (mAb) to cartilage proteoglycans. Anti-proteoglycan antibodies used in this study recognize complex epitopes of core protein segment associated with carbohydrate, shared by human cartilage proteoglycans and certain lymphoma cells. The binding of these antibodies was independent of cell-cycle phase. The results suggest that the anti-proteoglycan mAbs could be used as new phenotypic markers to individualize non-Hodgkin lymphomas.

Animals↗

New in vitro line from a human (B) non-Hodgkin lymphoma.

An in vitro cell line (HT 58) has been established from a human (B) NHL xenograft. The lymphoma cells in culture retained their lymphoblastic appearance, DNA-content, IgM/lambda monoclonality and many immunophenotypic markers. The clonal chromosomal abnormalities involved the chromosomes 1, 2, 3 and 14. The cells expressed and produced chondroitin sulfate proteoglycans identified with mAbs that were raised against human articular cartilage CSPG. The cells also released IgM into the medium as well as substances that stimulated the proliferation of activated normal peripheral B-cells.

Antibodies, Monoclonal↗

Lectin-binding pattern in human non-Hodgkin lymphoma xenografts.

The glycan profile of cell surface proteins has been studied on three human non-Hodgkin lymphoma xenografts of B-cell origin using a panel of biotinylated lectins. All three lines showed a more heterogeneous lectin-binding pattern than normal peripherial blood lymphocytes (PBLs) involving both the inner core and antenna part of the glycans. The conservative inner core (N-N-acetylchitobiose and oligomannose) was similar but fucosylated to various extents in the different lymphomas. The structure of the antennae of PBLs was characterized by glcNac-gal and galNac-gal-Sa sequences, while in lymphomas additional asialo as well as sialylated galNac containing antennae have been identified. This study suggests that NHLs sharing many immunophenotypic features show intertumoral differences in their lectin-binding pattern.

Animals↗

The invasive front of carcinomas. The most important area for tumour prognosis?

Various molecular events of importance in tumour spread, like the gain and loss of adhesion molecules, secretion of proteolytic enzymes, increased cell proliferation, and the initiation of angiogenesis occur at the tumour-host interface (invasive front). We have hypothesised that molecular or morphological characteristics at the invasive front area of various carcinomas may reflect tumour prognosis better than other parts of the tumour. Consequently, we recently developed a simple malignancy grading system restricted to the deep invasive front area of head and neck squamous cell carcinomas. This grading system proved to have additional prognostic value over the established prognostic factors. All similar studies performed so far have confirmed the high prognostic significance of the invasive front grading in squamous cell carcinomas at different locations. In this review paper we describe the system and the hypothesis on which it has been developed. The reproducibility of the grading is acceptable for further extended studies. Interestingly, observations of similar invasive front alterations in different adenocarcinomas suggest that the invasive tumour front may underlie the biological aggressiveness of carcinomas of glandular origin, as well.

Carcinoma, Squamous Cell↗