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Biomedical subjects

A Böcking

Publications and source records attributed to A Böcking.

141 records · Page 8Linked to original sources

Detection of high risk patients in chronic myelogenous leukemia by DNA-image cytometry.

Peripheral blood smears from the time of diagnosis of 64 patients with chronic myelogenous leukemia (CML) in chronic phase were restained according to Feulgen. Nuclear DNA content of at least 100 myeloblasts and promyelocytes was measured by interactive DNA-cytometry using a TV-image analysis system, combined with an automated microscope. From the resulting DNA values the DNA parameters stemline ploidy, stemline shoulder fraction and "proliferative" fraction, which reflect cytogenetic and cell kinetic characteristics of CML, were derived. Each of these DNA parameters identified subgroups with a significantly different survival time and duration of chronic phase. Indicators for a good prognosis were a near-diploid stemline ploidy (median survival time 49 v. 26 months), a low percentage of nuclei in the stemline shoulder fraction (45 v. 28 months) and a high "proliferative" fraction (45 v. 23 months). Independently of clinical and hematological features, the DNA-cytometric parameters yielded additional prognostic information both in the univariate and multivariate analysis.

Adult↗

Angioimmunoblastic lymphadenopathy--a malignant disease due to DNA aneuploidy.

Angioimmunoblastic lymphadenopathy (AIL) was considered by most authors in the 1970s as a non-malignant disease. However, it is widely accepted that many AIL cases would now be categorised as T-cell lymphomas of the AIL type. DNA measurements were performed on imprint smears from lymph nodes of 10 AIL patients to obtain further evidence for the malignancy of this disease. The 5c Exceeding Events (5cEE), representing the number of cells with a DNA content greater than 5c, excluding cells with 8c, 16c or 32c (+/- 12.5%), were taken as an index for aneuploid cells. 5cEE greater than or equal to 3 was considered to be evidence for aneuploidy and thus for malignancy. According to this definition of aneuploidy, malignancy was assumed in 9 cases out of 10. No aneuploid cells (5cEE = 0) were found in four patients with lymphadenitis.

Adult↗

DNA-grading of prostatic carcinoma: prognostic validity and reproducibility.

The prognostic significance of the DNA-Malignancy-Grade (DNA-MG) was tested in 52 prostatic carcinoma patients in comparison with a cytomorphological grading system and the clinical staging. Papanicolaou- or MGG stained smears from transrectal aspiration biopsies were automatically restained according to Feulgen in a modified Shandon staining machine. The DNA-MG, based on the variation of the nuclear DNA content of tumor cells around the normal DNA peak, ranges on a continuous scale from 0.01 to 3.0. It was determined with a TV-image analysis system (Leitz, TAS plus), combined with an automatic microscope. The DNA-MG revealed a high prognostic validity, the clinical stage showed only a minor influence on the survival time and the cytopathologic grading system was of insufficient prognostic information. Significant differences in survival time could be demonstrated between patients with DNA-MGs of 0.01-1.5 and 1.5-3.0, as well as with DNA-MGs 1.0-2.0 and 2.0-3.0. The intra- and interobserver variations of the DNA grading system were found to be sigma = 0.014 and sigma = 0.036 respectively. The reproducibilities were 86.7% for intra- and interobserver measurements, when the continuous DNA-MG scale was divided in three groups.

Aged↗

DNA-cytometric diagnosis of prospective malignancy in borderline lesions of the uterine cervix.

Interactive DNA cytometry was used for the diagnosis of prospective malignancy in 48 smears with borderline lesions (mild and moderate dysplasias) of the uterine cervix. In addition, 183 smears with benign squamous epithelia, 38 with carcinoma in situ and 7 with invasive squamous carcinoma were also measured. Nuclear Feulgen-DNA measurements were performed using various methods, and the resulting data were analyzed by an algorithm for a DNA-cytophotometric diagnosis of malignancy. The results were compared with the data on follow-up and subsequent histologic studies in these cases. There was no false-positive diagnosis in the 183 benign smears and only 1 false-negative diagnosis in the 76 histologically proven squamous-cell carcinomas, which yields a specificity of 100% and a sensitivity of 98.6%. The sensitivity for the detection of subsequent histologically proven malignancy in cases with cytologically mild or moderate dysplasia amounted to 97%. In 13 borderline cases, there was a mean interval of 21 months between the taking of the cytologic smear on which the DNA diagnosis of malignancy was made and the date on which the histologic confirmation of malignancy was made. In 17% of the cytologically dysplastic cases, the DNA diagnosis of malignancy was not verified by subsequent histologic investigation. These results indicate that interactive DNA cytometry is able to detect prospective malignancy in smears from borderline lesions of the uterine cervix with a high sensitivity.

Carcinoma in Situ↗

Exfoliative-cytologic diagnosis of basal-cell carcinoma, with the use of DNA image cytometry as a diagnostic aid.

Eighty-four skin lesions clinically suspected of being basal-cell carcinomas were investigated by exfoliative cytology. Specific criteria were found for the cytologic diagnosis of basal-cell carcinoma. All 37 cases of basal-cell carcinoma were correctly classified cytologically and could be differentiated from the 8 cases of squamous-cell carcinoma. There were no false-positive or false-negative diagnoses. Insufficient cellular material was obtained in 17% of the cases. The technique for collecting exfoliated epidermal cells with a new swab is described. DNA image cytometry was used as a diagnostic aid in doubtful cases. DNA image cytometry showed that 83% of the basal-cell carcinomas had an aneuploid nuclear DNA content.

Algorithms↗

DNA-grading of malignant lymphomas. I. Prognostic significance, reproducibility and comparison with other classifications.

The prognostic significance of the DNA Malignancy Grade (DNA-MG) was tested for 83 malignant non Hodgkin lymphoma patients in comparison with three different subjective morphological classification systems (New Working Formulation for Clinical Usage, Rappaport and Kiel Classification). Monolayer smears prepared from paraffin embedded tissue and imprint smears from fresh cut lymph-nodes were investigated. Feulgen staining was performed automatically. The scalar DNA-MG was determined by rapid interactive DNA-cytometry, using an automatic microscope and a TV-image analysis system. A strong influence of the DNA-MG on length of survival was found. Compared with morphological classification systems, the DNA-MG was of greater prognostic validity as revealed by different statistical tests. Significant differences of survival probabilities between some groups with differences of 0.5 DNA-MG only were found. The interobserver reproducibility of this new prognostic index was found to be 95% within a range of +/-0.4 DNA-MG.

Adolescent↗

DNA-grading of malignant lymphomas. II. Correlation with clinical parameters.

The clinical significance of the DNA-malignancy grade (DNA-MG) was tested in 90 malignant lymphoma patients. Feulgen stained imprint smears from freshly cut lymph-nodes were investigated. DNA measurements were performed using various cytophotometers. The scalar DNA-MG, ranging from 0.1 to 3.0, was calculated from the variance of the tumor cells around the 2c peak. Except for the CLL, all entities of the Kiel classification for non-Hodgkin's malignant lymphomas showed considerable variation of the DNA-MGs. The DNA-MG, the age of the patients and the response to treatment were seen to have a significant influence on the survival time of non-Hodgkin's lymphoma patients. In high grade lymphoma patients of the Kiel classification, the DNA-MG was found to provide additional prognostic information. The DNA-MG was strongly correlated with the ESR, low albumin concentration, low lymphocyte counts in peripheral blood, clinical and pathological staging, and the response to treatment.

Adolescent↗

DNA grading of urothelial carcinoma of the bladder.

The prognostic influence of the nuclear DNA distribution pattern of human urothelial carcinomas of the bladder was investigated in 25 patients. Nuclear DNA content was measured by scanning microphotometry in Feulgen-stained histologic sections. A DNA malignancy grade (DNA-MG) ranging from 0.01 to 3 on a continuous scale was computed for each patient from the single cell DNA values. With the aid of the Cox proportional hazard regression model, DNA-MG was revealed as having a strong influence on survival time (p = 0.0004). Possible influences of other parameters (histological grade, stage, endoscopical tumor size and multiplicity, age) on survival could not be assessed in this model. This may be explained by the low number of cases and by the weakness of the influence of these parameters. Divided into two groups of patients according to their DNA-MG (group I: DNA-MG less than 1.5, group II: DNA-MG greater than or equal to 1.5), the histological grade had an influence on survival (p = 0.021). There was a good association of DNA-MG and histological grade (p = 0.05). In comparison to the histological grade DNA-MG seems to allow a more precise prognostic statement for the individual patient as it reveals additional information on survival for patients categorized according to their histological grade. We conclude that DNA-MG is an objective and scalar index for the prognosis of bladder carcinoma patients.

Adult↗

Midline malignant reticulosis.

A combined histological, ultrastructural and cytological study was performed on biopsy materials from nasal lesions of 2 patients with midline granuloma. The histological and ultrastructural features of the tissues were necrosis, inflammation and infiltration of atypical histiocytic cells. The DNA-content of these histiocytes exceeded the limits of the 5c Exceeding-Rate and the 2c Deviation Index. The morphological characteristics and the results of the DNA-cytophotometry classify the midline granuloma as a local malignant histiocytosis. Clinical follow-up of the cases suggests that radiation therapy offers a good prospect of treatment success.

Adult↗

Cytologic versus histologic evaluation of needle biopsy of the lung, hilum and mediastinum. Sensitivity, specificity and typing accuracy.

Fine needle aspiration biopsy (FNAB) and punch biopsy (PB) are reliable methods of establishing a morphologic diagnosis in thoracic lesions. However, some reservations exist concerning the diagnostic accuracy of and indications for both methods. Therefore, we evaluated the sensitivity, specificity, typing accuracy and complication rates of both methods. We present a six-year experience with 501 thoracic FNABs and PBs in 482 patients. To examine site-specific differences, we evaluated three different compartments: lung, mediastinum and hilum. In 457 cases the final outcome was known for evaluating the accuracy of the cytologic or histologic diagnoses. FNAB was used most often in lung (81.8%) and hilar lesions (87.3%), whereas PB was used mostly in mediastinal (67.9%) and pleural lesions or if a mesenchymal lesion was suggested radiologically but never in foci below 20 mm in diameter. Our complication rate was 21.3% for FNAB and 4.6% for PB. The most frequent complications were pneumothorax, one hematothorax and intercostal neuralgia. The overall sensitivities of the biopsy methods were equal (FNAB, 98.4%; PB, 98%), but the typing accuracy was better for PB than FNAB (87.2% vs. 83.5%). In the hilum the sensitivities of FNAB and PB were 94.6% and 85.7%, respectively, and for the lungs, 99% and 98.2%. In the mediastinum the sensitivity was 100% for both methods. There were false-positive diagnoses in 5% with FNAB of the lung due to misinterpretation of regenerating epithelium and hamartochondroma and a 0.1% rate of false-negative diagnoses as a result of misplacement of the cannula, leading to inflammation, infarction or scarring. Our data indicate that FNAB is the method of choice in pulmonary and hilar lesions because of the similar diagnostic accuracy. Mediastinal and pleural lesions and presumed mesenchymal tumors should be sampled with PB because the typing accuracy of FNAB is insufficient in these cases.

Adolescent↗

DNA-image cytometry and clinical staging systems in multiple myeloma.

Clinical and hematological parameters, and three derived major staging systems were compared with DNA-cytometric parameters in 73 patients with newly diagnosed multiple myeloma (MM) and correlated in univariate analysis with survival to assess their predictive value. Regarding diagnostic validity, a multi-parameter system including STL, 5cER, PRF and MNA correctly classified 92% of MM as malignant (sensitivity 92%) at a 100% specificity. Regarding prognosis, the most powerful single clinical parameter was serum creatinine (p < 0.001, median survival [ms] 51 vs. 14 months) followed by platelet count (p < 0.01, ms 67 vs. 11 months). Mean nuclear area of plasma cells was the only cytometric parameter with prognostic relevance (p < 0.05, ms 43 vs. 14 months). Neither the original Salmon-Durie staging (p < 0.05 for I vs. II, p > 0.05 for II vs. III) nor the revised Salmon-Durie staging by Cavo et al were able to discriminate three patient groups at statistically significant levels. Only the staging system proposed by the British Medical Research Council (MRC) was found to be able to predict survival for all three groups significantly (p = 0.01 for A vs. B, p < 0.01 for B vs. C; ms A/B/C = 68/37/14 months, respectively).

Analysis of Variance↗

Principal component analysis. A factor analytical technique for the determination of interobserver variation in histomorphologic tumor grading.

The insufficient interobserver reproducibility limits the practical use of histomorphological tumor grading in daily routine pathology. In this study, the reasons for the quite low rates of agreement between different observers have been investigated by the application of a factor analytical technique, i.e. principal component analysis with varimax rotation, on a tumor grading system. Grading results from 44 cases of G1 and G2 giant cell tumors of the bone (GCT), graded by three different observers according to the five criteria of Jaffe, were taken as an example. It could be proven that the single criteria were used in an observer-specific way. Two criteria, for example, which are scored highly correlated by one observer, may be used independently by another. The resulting observer-specific different recognition patterns may provide an explanation for their quite different grading results, which were identical in only 48.6% to 54.1% (mean: 50.9%) of the cases. No correlation of GCT grading with recurrence was found in 31 cases which had been treated by intralesional surgery.

Adult↗

Interobserver reproducibility of immunocytochemical estrogen- and progesterone receptor status assessment in breast cancer.

The interobserver reproducibility in the immunocyto-chemical assessment of estrogen- and progesterone receptor status was investigated in a series of 102 cases of primary breast carcinomas. Immunostaining was performed on 4 microns cryostat sections using estrogen- and progesterone immunocytochemical assays (ER-ICA and PR-ICA) with methylgreen counterstaining. The slides were evaluated independently by two observers. The proportion and staining intensity of ER- or PR-positive tumor cells in areas of invasive tumor growth was subjectively assessed based on the examination of the entire slide. Scoring was performed according to the proposals of Remmele and Reiner. Additionally, the cytosol estrogen- and progesterone receptor content was determined by a standard dextran-coated charcoal (DCC-) assay. Observer 1 interpreted 60 (59%) of the ER-stained specimens and 50 (49%) of the PR-stained specimens as receptor-positive; for observer 2 the respective values were 59 (58%) for ER-stained specimens and 51 (50%) for PR-stained specimens. Positive biochemical receptor status was found in 68 cases with the ER-DCC (67%) and in 47 with the PR-DCC (46%). The interobserver agreement between the two observers on the immunocytochemical receptor status was 89% for the estrogen receptor and 93% for the progesterone receptor 8.8% of the specimens were interpreted differently. Using the Remmele score, the concordance within the group of cases, which had been interpreted as receptor-positive by both observers, was 54% for the estrogen receptor and 57% for the progesterone receptor. The Reiner score showed concordant scorings of 72% for the estrogen receptor and 79% for the progesterone receptor. The present study indicates that complete agreement between scorings of different observers may not be expected, mainly due to differences in the interpretation of the specificity of staining and of the histological structures after immunostaining. The concordance of positive results using the three-graded Reiner score is comparable to that of the three-graded Bloom and Richardson grading system of breast cancer and reflects the limitation of subjective evaluation of morphology in general.

Breast Neoplasms↗

Simultaneous immunohistochemical and biochemical hormone receptor assessment in breast cancer provides complementary prognostic information.

The prognostic value of the biochemical and the immunohistochemical assessment of estrogen- and progesterone receptor (ER, PR) status was tested in 111 breast cancer patients, mostly focusing on whether the results reveal complementary prognostic information. The biochemical receptor analysis was performed on snap-frozen tumor tissue using a standard protocol (ER-DCC, PR-DCC). The immunohistochemical staining was done on 4 microns thick paraffin sections and was evaluated semiquantitatively (ER-IHC, PR-IHC) and immunohistometrically by means of image analysis (ERMEAN, PRMEAN). 74% of the ER-DCC and 50% of the PR-DCC assays were interpreted as positive. The positivity rates of the immunohistochemical reactions ranged between 78% and 81% for ER and between 66% and 82% for PR, depending on the interpretation mode. The concordance rate for the DCC method was 68%, and ranged between 77% and 85% for the immunohistochemical results on paraffin sections. ER-DCC and PR-DCC showed a better survival for receptor-positive patients; however, this tendency was only statistically significant for the PR-DCC (p = 0.0294). Patients with immunohistochemically determined ER- or PR-positivity revealed a significantly better survival than receptor-negative patients, the effect being stronger for the progesterone receptor (ER: p = 0.0253, PR: p = 0.0005). Combining the different methods and receptors in a multivariate analysis, we observed that a) ER and PR reveal complementary prognostic information to each other after immunohistochemical determination (p < or = 0.0018) and that, b) complementary prognostic information was also obtainable by comparing the biochemical and the immunohistochemical PR-analysis (p < or = 0.0084); slightly more significant results were obtained for ERMEAN and PRMEAN compared to ER-IHC and PR-IHC. Considering the lymph node status and a combined receptor analysis (PR-DCC, ERMEAN, PRMEAN) as the two strongest prognosticators in multivariate Cox models, the combined receptor analysis was able to discover for each of the three groups of NO- and N1-patients different survival probabilities (p < 0.0001). In conclusion, the ER-DCC appears to be dispensable in all patients. In lymph node-negative patients, the PR-DCC has no outstanding merit, indicating that the neccessity of this method is also controversial. In priamry tumors of lymph node-positive patients, however, all three remaining types of receptor analysis should be evaluated for their therapeutic implications.

Breast Neoplasms↗