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Biomedical subjects

Agnes Bánkfalvi

Publications and source records attributed to Agnes Bánkfalvi.

9 recordsLinked to original sources
PubMed2005

Quantitative molecular urinary cytology by fluorescence in situ hybridization: a tool for tailoring surveillance of patients with superficial bladder cancer?

OBJECTIVE: To determine whether it is possible to stratify patients with superficial bladder cancer into low- and high-risk groups for tumour recurrence/progression based on the chromosomal pattern detected by fluorescence in situ hybridization (FISH) in one urine cytology specimen used for follow-up testing. PATIENTS AND METHODS: Voided urine samples from 47 consecutive patients with urinary tract neoplasms (13 with no history of urothelial malignancy and 34 under follow-up after complete transurethral resection of superficial urothelial carcinoma of the bladder) were evaluated by liquid-based cytology (ThinPrep(R), CYTYC Corp., Boxborough, MA, USA) and UroVysion FISH (Vysis-Abbott, Downers Grove, IL). RESULTS: Of the 34 patients under surveillance, the UroVysion test was negative in four, 17 had loss of 9p21 sequences either alone or combined with low-frequency trisomy/ies or tetrasomy/ies of chromosomes 3, 7 and 17 in single cells (low-risk FISH), and 13 also had complex aneusomies of the remaining chromosomes (high-risk FISH). One of the four FISH-negative neoplasms, four of the 17 low-risk FISH cases and five of the 11 informative high-risk FISH-positive patients developed recurrence. Progression occurred only in patients with high-risk FISH results, showing high-frequency complex chromosomal polysomies (four of 11). CONCLUSION: The results from this pilot study indicate that the UroVysion FISH test may help to individually assess the clinical behaviour of superficial bladder cancer, based on the chromosomal pattern of exfoliated tumour cells in follow-up urinary cytology. It might be of use to identify those patients likely to progress at earlier and curable stages of disease, and lengthen the surveillance period in those with persistent or recurrent low-risk disease.

Adult↗
PubMed2004

Different proliferative activity of the glandular and myoepithelial lineages in benign proliferative and early malignant breast diseases.

The aim of the present study was to explore cell biological characteristics of normal breast, benign proliferative breast diseases and noninvasive breast malignancies based on the recently published adult progenitor cell concept from our group. Here, we investigated the proliferative activity of CK5/14(+), CK8/18/19(+) and alpha-smooth muscle actin(+) cellular phenotypes encountered in normal mammary gland, in a series of usual ductal hyperplasias and early malignant breast diseases, such as atypical ductal and lobular hyperplasias, as well as ductal and lobular in situ carcinomas. Immunohistochemical double labeling was performed on frozen sections from diagnostic breast biopsies by using antibodies to basal cytokeratins (CK5/14), glandular cytokeratins (CK8/18/19), smooth muscle actin and the Ki-67 antigen (MIB1). Normal breast tissues and usual ductal hyperplasias were characterized by a heterogeneous cellular composition of the growth fraction. The proliferative cell compartment consisted of CK8/18/19(+) glandular and, in a variable proportion, CK5/14(+) progenitor phenotypes. In contrast, noninvasive breast malignancies were composed of a monotonous proliferation of CK 8/18/19(+) neoplastic glandular cells. These findings indicate a significant role of progenitor cells in the development of benign proliferative breast diseases and lend support to the view that malignant transformation in the human breast usually occurs in a cell committed to the glandular lineage. Our results provide cell kinetic support to the functional progenitor cell hypothesis, and we propose this concept as an operative model for understanding benign proliferative and malignant breast diseases.

Actins↗
PubMed2004

Comparison of automated and manual determination of HER2 status in breast cancer for diagnostic use: a comparative methodological study using the Ventana BenchMark automated staining system and manual tests.

This study was performed to test the validity of manual and automated HER2 tests in one hundred routinely formalin-fixed and paraffin-embedded diagnostic breast carcinoma tissues. Immunohistochemical (IHC) and fluorescence in situ hybridization (FISH) assays for HER2 were separately carried out in two institutes of pathology specialised in diagnostics of breast diseases. Manual immunostaining was performed by the Dako-HercepTest. Automated IHC and FISH were carried out in the Ventana BenchMark platform by using the Pathway-CB11 antibody and the INFORM(R) HER2 probe, respectively. Positivity rates varied between HercepTest (26%), automated CB11 IHC (23%) and automated FISH (22%). Overall concordance between positive (2+, 3+) and negative (0; 1+) results of manual and automated IHC was 97%, between automated FISH and IHC 92%, and between automated FISH and HercepTest 89%. The frequency of 2+ IHC scores was 13% using the BenchMark and 14% with the HercepTest; 6/12 and 8/14 of the respective cases were not amplified by FISH. Automated FISH was not interpretable in 11 of 100 specimens. In the 89 informative cases, automated IHC resulted in increased specificity (92% vs. 88%), increased positive predictive value (73% vs. 64%) and increased efficiency (92% vs. 89%). We conclude that automation improves the accuracy of HER2 detection in diagnostic breast carcinoma tissues and provides a new approach for the global standardization of clinical HER2 tests.

Benchmarking↗
PubMed2003

[HER-2 diagnostics].

HER-2 (c-erbB2, neu) receptor is the molecular marker of ductal breast cancer although it is verexpressed in other adenocarcinoma as well (e.g.endometrial, colorectal and lung cancers). The increased receptor expression is most frequently (90-97%) due to gene amplification. Detection of the overexpression of HER-2 helps to determine prognosis, to predict chemoresistance and to select for Herceptin therapy. HER-2 overexpression can be estimated either by immunohistochemistry or by fluorescent in situ hybridisation (FISH). Standardization of the immunohistochemical HER-2 tests is the best in HercepTest DAKO), however, the frequent 2+level requires complementary FISH test to verify gene amplification. This combination is not necessary at low (0-1+) or high (3+) level of immunohistochemical reactions, because the correlation with gene amplification status is acceptably high. Recently several new anti-HER-2 antibodies have been introduced into HER-2 diagnostics in various countries. According to our experiences we recommend to combine rationally the immunohistochemistry and FISH techniques to determine the HER-2 status in breast cancer.

Adenocarcinoma↗
PubMed2003

Relationship between HER2 status and proliferation rate in breast cancer assessed by immunohistochemistry, fluorescence in situ hybridisation and standardised AgNOR analysis.

Lack of standardisation and inaccuracy in HER2 test results may adversely influence patient evaluation and therapy selection. In the present study we applied immunohistochemistry (IHC) using the A0485 and CB11 antibodies and fluorescence in situ hybridisation (FISH) for detection of HER2 in 74 routinely processed breast carcinoma specimens. The rapidity of cellular proliferation was assessed by standardised AgNOR analysis and compared with HER2 status. Protein over-expression was found in 30/74 cases by A0485 and in 20/74 by CB11 antibodies, while amplification was detected in 22/74 carcinomas by FISH. Twenty-seven of 74 tumours were high-level AgNOR expressors (mean AgNOR area >3.369 microm2), 19 of which revealed amplification. The highest concordance between results was achieved by FISH and CB11-IHC (97%), the concordance between FISH and A0485-IHC was 89 and 84% between FISH and AgNOR quantity, respectively. The overall concordance between A0485 and CB11-IHC was 85% with 10 incongruent cases, all scored 2+ by A0485 and 0/1+ by CB11. Eight of the discordant tumours were non-amplified by FISH and 7 were low AgNOR-expressors. Our results indicate that using CB11 antibody, a nearly complete agreement can be achieved between HER2 IHC and FISH in diagnostic paraffin material. Moreover, in 2+ positive IHC cases, the AgNOR analysis may represent an additional tool to select patients as candidates for Herceptin therapy due to the strong negative predictor value.

Breast Neoplasms↗
PubMed2002

Gains and losses of adhesion molecules (CD44, E-cadherin, and beta-catenin) during oral carcinogenesis and tumour progression.

The aim of this study was to define whether or not the impaired expression of CD44, E-cadherin (E-cad), and beta-catenin (beta-cat) correlates with the clinical evolution and prognosis of oral cancer. Ninety-three primary oral squamous cell carcinomas (OSCCs) with tumour-adjacent normal and/or dysplastic mucosa, 30 associated metastases, and 12 recurrences were immunostained for CD44s, -v3, -v4, -v5, -v6, -v7, -v9, E-cad, and beta-cat. In non-neoplastic epithelium, all molecules investigated were constitutively expressed in the basal layers. In the majority of dysplasias, immunoreactivity for all adhesion molecules was increased, but there was restricted loss for CD44s, E-cad, and beta-cat in a few cases. In carcinomas, a striking accumulation of CD44s, v3, v4, v9 and a loss of E-cad/beta-cat were observed at the invasive tumour front. In metastases and recurrences, besides a loss of CD44s, v4, v7, and E-cad, a significant increase of v9 was recorded, whereas CD44v5 and v6 remained unchanged. Clinically, reduced expression of CD44v3, E-cad, and changes of CD44v9 phenotype within the primary tumours correlated significantly with poor prognosis; decreased beta-cat expression was a predictive marker for nodal metastases. These findings indicate that there is some perturbed expression of adhesion molecules during the stepwise course of oral carcinogenesis and tumour progression. Distinct phenotypic alterations project poor prognosis, while others predict metastasis. Some of these restricted molecular changes may serve as potential targets for future antibody-based tumour therapy.

Biomarkers, Tumor↗
PubMed2002

Deranged expression of the E-cadherin/beta-catenin complex and the epidermal growth factor receptor in the clinical evolution and progression of oral squamous cell carcinomas.

BACKGROUND: Deranged expression and function of the E-cadherin/beta-catenin (E-cad/beta-cat) complex and the epidermal growth factor receptor (EGFR) have been implicated in the development and progression of carcinomas. METHODS: To estimate the role of these molecules in oral cancer, we investigated 75 primary oral squamous cell carcinomas (OSCCs) with adjacent normal and/or dysplastic mucosa, 30 paired metastases and 12 recurrences by immunohistochemistry. RESULTS: All three molecules were constitutionally expressed in the basal/parabasal layers of tumour adjacent 'normal' epithelium, in contrast to a significant increase of EGFR and heterogeneous expression of E-cad/beta-cat in dysplasia. In OSCCs, over-expression of EGFR correlated significantly with lower tumour grade and poor prognosis, loss of E-cad was a significant marker for shortened survival, reduced beta-cat staining was a predictive marker for lymph node metastasis. CONCLUSIONS: There is a perturbance in intercellular adhesion molecules and EGFR expression/function in oral cancer with major clinical impact. E-cad and beta-cat seem to inhibit EGFR to enhance the progression of OSCCs.

Biomarkers, Tumor↗
PubMedDate not supplied

Predicting treatment outcome in cervical diseases using liquid-based cytology, dynamic HPV genotyping and DNA cytometry.

BACKGROUND: In this study, our prospective experience with a multimodal follow-up protocol is summarized, with special emphasis on predicting the treatment outcome of cervical diseases. MATERIALS AND METHODS: Liquid-based cytology samples (ThinPrep) from 209 women exhibiting the whole spectrum of human papilloma virus (HPV)-related cervical diseases were investigated by cytology, PCR-based HPV genotyping and DNA cytometry pre-surgery. The first control cytology and type-specific HPV tests were performed at 3 months post-surgery. RESULTS: The success rate of surgery was 95% in eradicating high-grade cervical disease and 90% in eliminating the baseline HPV genotype. Treatment failure was significantly correlated with baseline cytology (p=0.011), resection margin status (p=0.016) and HPV positivity at 3 months post-surgery (p=0.04). Multivariate logistic regression analysis showed that type-specific persistent HPV infection (p=0.028), baseline cytology (p=0.039) and histology (p=0.065) were independent predictors of residual cervical neoplasias. CONCLUSION: Our results showed that our multimodal surveillance protocol may help to individually assess the anticipated clinical outcome of cervical diseases post-surgery.

Adolescent↗