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R Hofmann-Wellenhof

Publications and source records attributed to R Hofmann-Wellenhof.

66 records · Page 4Linked to original sources
PubMed1994

Pattern interpretation by cellular automata (PICA)--evaluation of tumour cell adhesion in human melanomas.

In routine pathology, the evaluation of the pattern of a tumour at scanning magnification often reveals diagnostic and prognostic features indicating that the biological properties of the tumour cells are related to the morphological pattern. For further evaluation of the relationship between functional properties of the cells on the one hand and the pattern on the other, we propose the pattern interpretation by cellular automata (PICA) procedure. The PICA system consists of an import module transferring real histological images into the data structure of a cellular automaton, a measurement module generating a comparable quantitative description of real and simulated images, a cellular automation designed to simulate tumour growth and invasion at the histological level, a database consisting of the morphological results obtained in simulated patterns, an interpretation module linking real histological images to the knowledge stored in the database and an image synthesis and display module. By comparing real images to computer-simulated patterns, PICA facilitates an estimation of functional properties based on the static histological pattern of a given tumour. Using the example of tumour cell adhesion, it is demonstrated that the degrees of tumour-tumour and tumour-stroma adhesion significantly affect the resulting simulated patterns, that, in turn, the morphological evaluation of the patterns enables a reproducible estimation of adhesion and that estimates of adhesion in real images of malignant melanoma of the skin are of prognostic significance. PICA may serve as an additional in situ evaluation technique linking morphological features to functional properties.

Cell Adhesion↗
PubMed1993

Proliferative activity in Spitz's naevi compared with other melanocytic skin lesions.

Proliferative activity has been shown to correlate with the degree of malignancy in various human neoplasms. Immunostaining with the monoclonal antibody PC10 binding to proliferating cell nuclear antigen (PCNA) facilitates the assessment of proliferation in routinely fixed, paraffin-embedded tissue sections. In this study we investigated the expression of PCNA in 29 Spitz's naevi in comparison with 43 primary malignant melanomas (MM), 18 cutaneous metastases of malignant melanoma (MMM) and 16 benign melanocytic naevi (BMN). After selection of the microscopic field with the highest number of PCNA-positive nuclei, the nuclear density (NDmax) of PCNA-stained nuclei in this field was assessed using interactive image analysis. The mean value of NDmax (given as 1000 nuclei/mm3 tissue) of SN was 27.9 (+/- 16.7) and differed significantly from that of MM (48.1 +/- 40.5; U-test: p < 0.05) and that of MMM (114.4 +/- 56.3; p < 0.01). Comparing NDmax of the subgroups of MM according to their maximal vertical tumour thickness with NDmax of SN we found significant differences only between SN and MM > 1.5 mm thick (n = 14; NDmax = 67.8 +/- 36.1) but not between SN and MM < or = 1.5 mm thick (n = 29; NDmax = 38.8 +/- 39.3). PCNA expression in SN did not differ from that of BMN (NDmax 23.8 +/- 28.5). Proliferative activity as assessed by measurement of PCNA expression therefore showed significant differences between BMN, SN and thin primary melanomas on one hand and thick primary melanomas and cutaneous metastases of malignant melanomas on the other hand.

Antigens, Neoplasm↗
PubMed1993

Comparison of proliferative activity as assessed by proliferating cell nuclear antigen (PCNA) and Ki-67 monoclonal antibodies in melanocytic skin lesions. A quantitative immunohistochemical study.

Immunostaining with the monoclonal antibodies PCNA and Ki-67 provides a simple method for the assessment of growth fractions of tumors. Contrary to Ki-67, PCNA antibody can be applied on aldehyde- or alcohol-fixed and paraffin-embedded tissues, thus allowing studies on archival material. For 77 melanocytic skin lesions, we compared PCNA immunostaining on formalin-fixed tissue with Ki-67 immunostaining on frozen material of the same lesion. 16 benign melanocytic nevi (BMN, from 16 patients), 43 primary malignant melanomas (PMM, 42 patients), and 18 skin metastases of malignant melanoma (MMM, 12 patients) were included in the study. Maximum nuclear density (NDmax) of PCNA- and Ki-67-positive nuclei was assessed using interactive image analysis. NDmax values for both PCNA and Ki-67 differed significantly between the three diagnostic groups (Kruskal-Wallis H-test: p << 0.001). Mean values (given as 1000 nuclei/mm3 tissue) increased considerably from benign to malignant lesions (PCNA: BMN: 23.8 +/- 28.4 [mean +/- standard deviation], PMM: 48.1 +/- 41.0, MMM: 117.0 +/- 64.6; Ki-67: BMN: 6.4 +/- 3.3, PMM 25.0 +/- 31.1, MMM: 95.2 +/- 47.2). Correlation between NDmax values of PCNA- and Ki-67-positive nuclei was significant (Linear regression analysis: r = 0.51, p << 0.001). Furthermore, for PMM a significant correlation between histologic parameters related to prognosis (Breslow index and mitotic rate) and PCNA as well as Ki-67 expression was found (PCNA-Breslow index: r = 0.42, p < 0.01; Ki-67-Breslow index: r = 0.60, p << 0.001; PCNA-mitotic rate: r = 0.40, p < 0.01; Ki-67-mitotic rate: r = 0.50, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1993

Mediastinal mass caused by syphilitic aortitis.

A 47 year old man presented with hoarseness and chest pain found to be due to proliferative syphilitic aortitis. The case is unusual as the syphilitic aortitis caused a mediastinal mass without affecting the lumen of the aorta.

Humans↗
PubMed1993

Quantitative effects of intercellular signals on computer-simulated tumor patterns.

The behavior of tumor cells within a particular in vivo microenvironment is considered to be regulated by intercellular signals. Previous studies of computer simulations of tumor growth demonstrated a qualitative effect of autocrine and paracrine signaling factors on the resulting morphologic patterns. We investigated the quantitative effect of these intercellular signals when the evolving patterns were evaluated by a set of pattern analysis procedures, yielding 18 quantitative morphologic features. The results show that both autocrine and paracrine factors regulating either tumor cell proliferation, motility or death influenced at least 10 of the 18 features significantly (linear regression analysis; n = 50 for each experiment; P = < .01). Furthermore, multivariate analysis of 600 simulated patterns also demonstrated highly significant relationships between intercellular signals and quantitative features of the evolving pattern (P = < .001). The study showed that various pattern measurement features indicate a direct influence of intercellular signals on tumor patterns in computer simulations.

Cell Communication↗
PubMed1993

Tumor cell proliferation and motility estimates are prognostic factors in malignant melanoma.

Metastatic spread of solid tumors depends on a complex metastatic cascade. Metastatic tumor cells must therefore express a variety of biological properties including the ability to proliferate and the ability to migrate. In the present study, the prognostic significance of both parameters was investigated in 184 cases of malignant melanoma of the skin. Proliferative activity was assessed by mitotic counts, the degree of cell motility was estimated by comparing the histological pattern of the tumor with patterns obtained by computer simulations with predefined values of cell motility. Follow up of surviving patients was at least 5 years. Statistical analysis was done using classification and regression tree (CART) analysis combining mitotic counts and motility estimates. As far as overall survival was concerned, mitotic counts were the most significant variable separating one group of patients with mitotic counts < 17/mm2 and a 5-year survival rate of 82% and a group with mitotic counts > or = 17/mm2 and a 5-year survival rate of 52%. Within the group with low mitotic counts, motility estimates found a subgroup of patients with a coefficient of motility > or = 126, which had a 5-year survival rate of 55% similar to those patients with high mitotic counts. Corresponding results were obtained in the assessment of metastasis-free interval. The data show that not only proliferation as assessed by mitotic counts, but also estimates of tumor cell motility based on image analysis and computer simulations provide prognostic information in primary malignant melanoma of the skin.

Cell Division↗
PubMed1992

Prognostic significance of proliferation and motility in primary malignant melanoma of the skin.

The metastatic cascade depends on the presence of tumor cells which are capable of proliferation as well as of invasion with active motility. In the present study, it was examined whether the demonstration of both features in the primary lesion of malignant melanoma of the skin carries prognostic significance. Proliferation was assessed by mitotic counts and Ki 67 staining, and motility was estimated by image analysis and comparison of the image analysis results with computer simulations; 27 cases of primary malignant melanoma with a maximum vertical tumor thickness exceeding 1 mm were prospectively sampled. Mitotic counts were carried out on H & E stained sections, image analysis of the tumor pattern on S-100 immunostained paraffin slides, and Ki 67 labeling of actively cycling cells was evaluated on frozen sections. Neither proliferation nor pattern analysis alone provided a significant prognostic result with respect to overall survival and to metastasis free survival. The estimates of motility, derived from a combination of pattern analysis and proliferation values, however, proved to be significant predictors of overall survival and metastasis-free survival (log rank test: p less than or equal to 0.05). The motility features were superior to Clark level and Breslow index in this set of cases. The results demonstrate that the assessment of tumor cell proliferation and motility in histological sections may reflect the metastatic potential of primary malignant melanomas of the skin.

Cell Division↗
PubMed1990

The influence of staining procedures on the assessment of cell proliferation as defined by the monoclonal antibody Ki-67.

We examined the influence of different staining techniques [(three-step immunoperoxidase technique (IP); alkaline phosphatase-anti-alkaline phosphatase technique (APAAP)] on the quantitative evaluation of Ki-67-labeled nuclei. We studied five melanocytic skin tumors. From each case, five parallel sections were prepared and stained using the peroxidase-antiperoxidase (PAP) technique (slide 1) and the APAAP technique once (slide 2). Slide 3 consisted of a single repetition of the APAAP technique, slide 4 was a double repetition, and slide 5 was a third repetition. We assessed the volume fraction (VV) of Ki-67-positive nuclei using computer-assisted image analysis. For each staining group, the mean value and standard deviation of VV were calculated. Comparing VV values obtained from the different staining groups we did not find a statistically significant difference between the IP and the various APAAP steps (Wilcoxon test, p = less than 0.05). However, the staining procedure influenced the quantitative results to some extent. The mean VV of the five staining groups ranged in our study from 0.10 to 0.17%, which is narrow compared with the overall variability among different cases (dermal melanocytic nevus, 0.01%; metastatic malignant melanoma, 0.43%). Therefore, we can state that for a rough evaluation of Ki-67-positive nuclei, the influence of different staining methods is negligible; for a subtle quantitative analysis, however, it would nevertheless be preferable to always apply the same staining technique.

Antigens, Surface↗
PubMed1989

Vascular architecture of melanocytic skin tumors. A quantitative immunohistochemical study using automated image analysis.

The present study examines the distribution of blood vessels in melanocytic skin tumors. Fresh frozen sections of 11 cases each of benign nevocellular nevus, primary malignant melanoma and metastatic malignant melanoma were stained with the endothelium-specific monoclonal antibody BMA 120 and evaluated by an automated image analysis system. Additionally, the proliferative activity was assessed in parallel sections using Ki 67 monoclonal antibody. There were only slight differences between the diagnostic groups as to the vascular distribution in the tumor center, but there were remarkable differences in the connective tissue at the base of the lesions: The area occupied by small vessels (minimum diameter less than 20 microns) was 0.3 +/- 0.05% in benign nevi, 0.6 +/- 0.05% in primary malignant melanoma, and 1.2 +/- 0.10% in metastatic malignant melanoma (U-test: p less than or equal to 0.05). The proliferative activity within each lesion showed a strong positive correlation with the number of small vessels at the base of the tumor (linear regression analysis: r = 0.86; p less than or equal to 0.0001). The findings demonstrate that neovascularization in malignant melanocytic tumors takes place predominantly in the surrounding host tissue and is closely related to the proliferative activity.

Adolescent↗
PubMed1989

Nuclear size and shape parameters correlate with proliferative activity in cutaneous melanocytic tumors.

Proliferative activity and morphometric data have previously been shown to be related with the degree of malignancy in melanocytic skin tumors. In the present study, the proliferative activity, as defined by Ki 67 monoclonal antibody (reactive with all actively cycling cells), has been determined by immunohistologic and morphometric methods in cutaneous melanocytic tumors. Quantitative morphologic features of Ki 67-positive and Ki 67-negative nuclei were separately assessed using computer-assisted image analysis. Comparing morphometric features and proliferative activity, the most significant correlation was found between mean nuclear volume and the percentage of Ki 67-positive nuclei in each lesion (linear regression analysis: r = 0.73; p = less than 0.05). On multidimensional discriminant analysis, tumors with high proliferative activity (more than 5 X 10(3) Ki 67-positive cells per mm3 tumor tissue) were detected at a specificity of 92% and a sensitivity of 75%. Within one lesion, Ki 67-positive nuclei showed an increase in nuclear volume (Wilcoxon test: p = less than 0.05), a more spheroid shape (p = less than 0.05), and a wider dispersion of nuclear volume values (Siegel-Tukey test: p = less than 0.05) than negative nuclei. Discriminant analysis on the basis of nuclear volume density functions facilitated an estimation of the proliferative state (resting or cycling) of a given nucleus. The results are consistent with increased cellular synthetic activity in highly proliferating lesions and particularly in actively cycling cells. The association of proliferative activity and quantitative nuclear features may be helpful in the interpretation of morphometric studies concerning melanocytic skin tumors.

Antibodies, Monoclonal↗
PubMedDate not supplied

Hexadecylphosphocholine inhibits invasion of mouse T-cell lymphoma cells in two different invasion assays.

Hexadecylphosphocholine (HePC), an ether lipid analogue, is a new antineoplastic drug which has been shown to exert a remarkable antiproliferative effect in vitro and in vivo. The signal transduction pathway and the phospholipid synthesis are thought to be the main putative molecular targets of HePC, yet the exact mechanism of action is still unclear. To investigate the antiinvasive activity of HePC on a mouse T-cell lymphoma cell line (BW-O-Li1), we used a type I collagen gel and devitalized dermis as substrate to evaluate the migration of BW-O-Li1 after exposure to HePC. BW-O-Li1 cells were exposed for 24 h to a non-cytotoxic (10 microM) as well as to cytotoxic concentrations of HePC. Afterwards, BW-O-Li1 cells were seeded on top of a reconstituted collagen gel layer or pippeted into a steel ring placed on the dermal site of a devitalized dermis. Lymphoma cells, which invaded the collagen layer were counted by light microscopy, invasion into devitalized dermis was measured by an image analysis system. Compared to unexposed cells, invasion into the collagen gel differed significantly even at 10 microM HePC, whereas the absolute number of invading cells, independently of the HePC concentration, showed no difference in the amount of counted cells. Migration into devitalized dermis was significantly reduced for 10 microM and 40 microM HePC. These data show that complementary information can be obtained by application of the two invasion assays and that the antiinvasive effect of HePC emerges at non-cytotoxic concentrations of the substance.

Animals↗