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Biomedical subjects

I Ruschenburg

Publications and source records attributed to I Ruschenburg.

34 records · Page 2Linked to original sources

Reverse transcriptase polymerase chain reaction for detecting Ewing's sarcoma in archival fine needle aspiration biopsies.

OBJECTIVE: Previous studies on pediatric soft tissue sarcomas have demonstrated a chromosomal 11;22 (q24;q12) translocation in Ewing's sarcoma (ES) and peripheral primitive neuroectodermal tumors that appears to be a unique oncogenic marker. To investigate the usefulness of reverse transcriptase polymerase chain reaction (RT-PCR) as an ancillary method for cytodiagnosis, we tested archival aspirates derived from ES patients to establish whether any beta-actin RNA expression or tumor-specific EWS/FLI-1 gene translocation had occurred. STUDY DESIGN: Sixteen skeletal specimens aspirated 10-15 years earlier from patients with cytologic and histologic diagnoses of ES were prepared for PCR. The amplification products were sequenced. RESULTS: Amplifiable RNA was detected in smears from 12 patients by beta-actin RT-PCR. Seven aspirates from beta-actin-positive patients showed ES-specific genomic translocation (58%). Sequence analysis of the resulting PCR fragments revealed EWS/FLI-1 fusion transcriptions of varying length. CONCLUSION: When RNA was retrievable, RT-PCR applied to routinely stained aspirate smears was a highly specific method in differential diagnosis of ES.

Base Sequence↗

Loss of DNA-mismatch repair gene expression in oral melanomas.

The defect of DNA mismatch repair is postulated to be responsible for malignant transformation in many types of tumours. The main aim of this study was to evaluate the expression of DNA mismatch repair proteins in 29 cases of oral melanomas and to relate this to the ploidy status of the lesions. MLH1 expression was found in 4/29, MSH2 in 6/29, PMS2 in 2/29 and PMS1 in 0/29 cases investigated. The range of positively stained cells did not exceed 50% with MSH2, and PMS2, or 5% with MLH1. Loss of the DNA mismatch repair gene expression correlated with high aneuploidy ratio, observed in totally negative cases.

Adaptor Proteins, Signal Transducing↗

How can one explain aneuploidy status in fibromatous and lipomatous naevus cell naevus?

34 lightly fibromatous, 23 heavily fibromatous, 5 lipomatous and 10 naevus cell naevi were stained with Feulgen kit in order to evaluate their ploidy status with CAS 200 image analyzer. 26/34 lightly fibromatous, 18/23 heavily fibromatous, and 5/5 lipomatous naevi were either suspicious for aneuploidy (Auer III) or clearly aneuploid (Auer IV). In contrast all 10/10 naevus cell naevi were euploid. Proliferation (S-phase) was not increased in naevi fibromatously and lipomatously changed. The mechanisms leading to aneuploidy are discussed.

Adult↗

Expression of DNA mismatch repair genes in naevi.

The significant difference of DNA mismatch repair genes expression between naevi and melanomas was demonstrated by our research group in the previous study. The main aim of this study was to compare the expression of MLH1, MSH2, PMS1 and PMS2 in 31 naevus cell naevi, 12 fibromatous naevi and 30 dysplastic naevi. The expression of DNA mismatch repair proteins was found in all naevi investigated. However, the expression (percentage of positively stained cells) was significantly higher in naevus cell naevi than in dysplastic and fibromatous ones.

Adaptor Proteins, Signal Transducing↗

Image cytophotometric DNA analysis of cystadenolymphomas.

Warthin's tumour of the parotid gland is generally a benign lesion, consisting of an epithelial and a lymphoid component with unclear histogenetic relationship, 17 cases of Warthin's tumour were investigated for ploidy related parameters by the image analysis system CAS200. All cases investigated were euploid. A diploid DNA pattern (Auer type I) was detected in 7/17 (41%) cases both in the epithelial and lymphoid component of the same tumour. In addition to a diploid cell fraction a tetraploid cell component was found in 7/17 (41%) cases, coincidentally, in the epithelial and lymphoid component (Auer type II). Euploidy in all investigated cases is in agreement with the generally benign nature of Warthin's tumours. The similarity of the DNA pattern (Auer type) in the genetically unrelated epithelial and lymphoid components in most cases (84%) is suggested to be related to a similar functional state of these two components and is discussed in relation to the histogenesis of cystadenolymphomas.

Adenolymphoma↗

Relevance of ploidy related parameters for prognosis in malignant fibrous histiocytomas.

Ploidy associated parameters were determined in 161 malignant fibrous histiocytomas (MFH) by DNA image cytometry. The rate of euploid cases in MFH with histopathological grade I was 42%, grade II 16% and grade III 6%. Univariate analyses showed that cases with a low percentage of diploid cells (< 40%) and cases with high rates of aneuploid cells between 4c and 8c (> 9%), octaploid cells (> 0%) and 16-ploid cells (> 0%), high 2.5c (> 60%) and 5c (> 16%) exceeding rates and cases with high DNA indices of the first (> 1.08) and the second (> 3.78) peak had significantly reduced survival rates. Multivariate analyses with Cox regression demonstrated that in addition to grade, only the percentage of aneuploid cells between 4c and 8c, the 5c exceeding rate and the DNA index of the first peak had independent prognostic impact. It was concluded that besides ploidy status and grading, ploidy associated parameters are suited for prediction of survival in MFH.

Adolescent↗

Myoepithelial sialadenitis versus low-grade non-Hodgkin's lymphoma of the salivary gland in FNAB: is discrimination by means of an image processing system possible?

The diagnosis of myoepithelial sialadenitis (MESA) in fine needle aspiration biopsy may be difficult. There is a dense lymphocytic infiltration in the gland and discrimination between a hyperimmune reaction and a low grade non-Hodgkin's lymphoma (NHL) of B-cell origin may be impossible. To get additional diagnostically helpful criteria, texture feature analysis on routinely obtained FNAB's of the salivary gland was applied. In the data set 36/36 cases of low grade B-NHL confirmed by histology and 10/13 histologically confirmed cases of MESA could be classified correctly by means of an image processing system. The chromatin structure of each nucleus was classified by texture features (n = 6), which were determined according to the method of Harms et al. For statistical analysis of the cell types a classification tree based on the commercial program CART was applied. The data set of 49 cases was proved by the crossvalidation test 10 fold. The calculated diagnosis for each case suggests that this method may be helpful in the cytologically doubtful cases.

Biopsy, Needle↗

Comparison of the DNA content in the different steps of cutaneous carcinoma progression.

The main aim of this study was to check the application of ploidy related parameters for differential diagnosis between solar keratosis, Bowen's disease and squamous cell carcinoma of the skin. 10 specimens of normal epidermis, 68 solar keratoses, 50 cases of Bowen's disease and 10 squamous cell carcinomas (SCC) were stained with Feulgen and their ploidy status was evaluated with a CAS200 image analyzer. Significant and highly significant differences between groups investigated not only for 5c exceeding rate, but also for the ratios of diploid, aneuploid, tetraploid, octaploid and 16-ploid cells are demonstrated. With respect to ploidy associated parameters solar keratosis is closer related to SCC of the skin than Bowen's disease. These findings are in accordance with a higher risk of progression to SCC inspite of a generally lower degree of atypia.

Adult↗

Prognostic significance of newly defined ploidy related parameters in melanoma.

5c exceeding rate is the parameter, most frequently showing prognostic impact. The CAS200 image analyzer makes possible the measurement of additional parameters defining single subfractions of cells, as for example the ratios of diploid, aneuploid, tetraploid, octaploid and 16-ploid cells. The main objective of this study was to define the prognostic significance of these new parameters in 106 primary melanomas with known survival time. 29 out of 106 melanomas were euploid. 77 out of 106 showed an aneuploid histogram. Multivariate analysis with Cox regression demonstrated that the percentage of aneuploid cells between 2c and 4c and the percentage of aneuploid cells between 4c and 8c, but not 5c exceeding rate, were able to influence survival time.

Adolescent↗

Relationship between GAGE-1/-2 expression, EBV infection and interferon-gamma expression in undifferentiated carcinoma of nasopharyngeal type.

GAGE-1/-2 proteins are novel tumour markers, functionally related to tumour rejection. The objective of the present study was to identify the existence of a relationship between GAGE-1/-2 expression, Epstein Barr Virus (EBV) infection and viral infection-induced cytokine expression in cultivated tumour cells and archival specimens of undifferentiated carcinoma of nasopharyngeal type (UCNT). PCR and in situ hybridization techniques were employed. In cultivated UCNT cells, interferon-gamma (IFN-gamma) induced synthesis of GAGE-1/-2 mRNA. In archival tumour specimens (n = 10) however, GAGE-1/-2 gene expression was detected in only 3/8 cases with coincident EBV infection and IFN-gamma expression. In conclusion, EBV infection appears to induce IFN-gamma gene expression in most tumors, but GAGE-1/-2 expression in only some tumours. The role of IFN-gamma and other factors in triggering GAGE-1/-2 gene activation must be elucidated further. The relevance of GAGE-1/-2 gene expression and its detection by PCR for future immunotherapy is discussed.

Adolescent↗

Proliferative activity in the progression of pigmented skin lesions, diagnostic and prognostic significance.

Proliferative compartments of a tumour can be determined cytophotometrically, by in situ hybridisation or by immunohistochemical detection of Ki67 antigen. The main objective of this study was to analyse the proliferative activity during the progression of pigmented skin lesions with respect to differential diagnostic and prognostic applications. The material investigated consisted of 209 pigmented skin lesions (31 naevi, 30 dysplastic naevi, 106 primary melanomas, 20 lymphatic and 22 organ melanoma metastases). Comparison of the ratios of cells in the S-phase gained by two different methods (cytometry, in situ hybridisation) did not show any significant differences. The correlations between Ki67 and S-phase indices in every diagnostic group were highly significant. The results of forward and backward Cox regression were identical and only Ki67 showed an independent prognostic influence (p < 0.001, coefficient in regression 0.02) with change in risk 2% and confidence limit ranging between 1.1% and 2.9%.

Adolescent↗

Comparison of the DNA content in liver cell adenoma, hepatocellular carcinoma and regenerative nodules.

With regard to neoplasms of hepatocytes, diagnostic pitfalls have been reported for differentiation of liver cell adenoma (LCA) from well differentiated hepatocellular carcinoma (HCC). Since cytophotometric analysis of the DNA content with the help of image analysis has proven to be of diagnostic value in various neoplasms, we examined its ability to discriminate between LCA and HCC as well as regenerative liver nodules. The material investigated consisted of 54 cases of HCC, 10 benign liver tumours and 10 cases suspicious for HCC. All the benign liver tumours demonstrated an euploid histogram. 9 out of 10 borderline tumours were euploid while 1 out of 10 was suspiciously aneuploid. Among HCC, 21 out of 54 were euploid, 18 out of 54 suspiciously and 15 out of 54 clearly aneuploid. 5c exceeding rate differed significantly between benign liver changes and borderline lesions (p = 0.0474) as well as between borderline lesions and malignant tumours (p = 0.0108). We conclude that the use of image cytometry is helpful as an additional criterion for more diagnostic accuracy in morphologically difficult cases.

Adenoma, Liver Cell↗

p53 and MDM2 protein expression in squamous cell carcinoma and neighboring dysplasia from the upper aerodigestive tract.

BACKGROUND: The identification of genetic changes in preinvasive epithelial lesions may provide markers for a better assessment of the progression potential. MATERIALS AND METHODS: p53, MDM2 and PCNA immunophenotypes were examined in 57 cases of squamous cell carcinoma (SCC) of the upper aerodigestive tract and the adjacent normal and dysplastic epithelia. RESULTS: PCNA index increased with increasing grade of dysplasia. p53 protein was expressed in 35% and MDM2 protein in 33% of SCCs. The p53 protein was expressed in 89% of mild and moderate and in 93% of severe dysplasia and carcinoma in situ adjacent to p53-positive SCCs. The MDM2 protein was expressed in 30% of mild and moderate and in 54% of severe dysplasia and carcinoma in situ adjacent to MDM2-positive SCCs. Preinvasive lesions adjacent to negative SCCs stained negative. CONCLUSIONS: p53 protein was detected more frequently in preinvasive lesions than MDM2 protein and seems to be of greater value as a biomarker.

Adult↗

Radiation induced early nuclear changes in cytologic brush specimens from the upper aerodigestive tract.

OBJECTIVE: To evaluate the feasibility of DNA image cytometry to assess radiation induced early nuclear changes in cytologic smears from the upper aerodigestive tract. METHODS: 100 cytologic brush specimens from 50 postoperatively irradiated patients with upper aerodigestive tract carcinoma were examined Smears were taken from clinically inconspicuous mucosa from the former tumor site and from a control region (contralateral side). Cellular DNA was quantified using the CAS 200 image analysis system on Feulgen stained slides. DNA histograms were evaluated using the coefficient of variation (CV), the DNA index (DI), the 2c deviation index (2cDI) and the 2.5c exceeding rate (2.5cER). RESULTS: All specimens from the control region were diploid. Forty-six smears from the former tumor region were diploid and in four cases non-diploid cells were found. Single cells with a DNA content exceeding 5c ('5c exceeding events'), were identified in three non-diploid and six diploid smears from the former tumor region. CONCLUSION: DNA analysis is a useful tool in detecting early nuclear changes preceding morphologic changes.

Adult↗

Fine needle aspiration cytology of focal nodular hyperplasia of the liver.

In five cases, the fine needle aspiration (FNA) cytologic study of ultrasonically detected solitary liver tumors yielded a diagnosis of focal nodular hyperplasia. Cytomorphologically, the lesions were characterized by the presence of both abundant normal hepatocytes and numerous epithelial cells in ductal formations, clusters or tightly packed groups in the FNA samples. In two of the five cases, the cytologic diagnosis was confirmed by subsequent histologic studies; in the remaining three cases, the clinical data were consistent with focal nodular hyperplasia of the liver. All five patients were women, four of whom had used oral contraceptives for long periods of time (5 to 15 years), which has previously been linked to the development of focal nodular hyperplasia of the liver. Based on the findings in this study, FNA cytology should be adequate for making the differential diagnosis of focal nodular hyperplasia versus liver-cell adenoma when solitary liver tumors are detected in such cases; it can yield a morphologic diagnosis and facilitate the decision as to whether surgical intervention is required.

Adult↗

Comparative cytophotometric analysis of reactive lymphoid hyperplasia and low malignant non-Hodgkin lymphoma.

In fine needle aspiration biopsy (FNAB) of lymph nodes, differential diagnosis between reactive lymphoid hyperplasia (RLH) and low grade non-Hodgkin lymphoma (NHL) may be sometimes difficult. Cytophotometric analysis of DNA content using image analysis has found practical application in the determination of malignancy in different tumours. In this study, image cytometry was applied to compare the ploidy status of the above mentioned lesions to obtain diagnostically helpful information. Thirty smears of histologically proven low grade NHL (10 follicular lymphomas of centroblastic-centrocytic type, 10 lympho-plasmocytoid immunocytomas, 10 chronic lymphocytic leukemias) and 15 smears of RLH were stained with Feulgen and examined by image analysis (CAS 200, Becton Dickinson). The 5c exceeding rate was determined according to the Boecking's definition of aneuploidy. Concerning the histogram types the Auer classification was used. The aneuploidy was found in 4/10 follicular lymphomas and 4/10 lymphoplasmocytoid immunocytomas. All chronic lymphocytic leukemias were diploid. In none RLH a 5c exceeding rate was found. The results verify the value of image cytophotometry as a helpful method in some diagnostically difficult cases.

Adolescent↗