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M Aubele

Publications and source records attributed to M Aubele.

At least 37 records · Page 2Linked to original sources
PubMed1996

Analysis of DNA and morphometry in breast carcinoma.

Feulgen-stained imprints and smears from 730 cases of invasive breast cancer were investigated using an image analysis system. From each tumor sample 100 cells were randomly scanned and several DNA and morphometrical parameters evaluated. Their prognostic value for a prediction of distant metastases within 5 years was investigated with the multivariate Cox regression analysis, which was performed for all consecutive cases, as well as for node-negative and node-positive patients separately. The multivariate analyses showed a strong prognostic value of the anisonucleosis (variation of nuclear radius) and the DNA histogram type in addition to the nodal status, the tumor size (pT), and the histological tumor grade. However, performing this analysis for both node-positive patients and for those without lymph node metastases demonstrated a different prognostic meaning of the variables. The combination of each of the group-specific variables led to a prognostic factor, which allowed an assignment of patients to several subgroups with significantly different risk for distant metastases. Thus, both a low-risk group of node-negative patients with a 5-year distant recurrence rate of only 5.8%, and a higher risk group of node-negative patients with a recurrence rate of 38.6% could be identified. Among the node-positive patients, a low-risk group with a distant recurrence rate of 8.6%, and also a high risk group with 69% distant recurrence, could be identified.

Adult↗
PubMed1995

Different risk groups in node-negative breast cancer: prognostic value of cytophotometrically assessed DNA, morphometry and texture.

Feulgen-stained imprints and fine-needle aspirates from 528 lymph-node-negative breast cancers were investigated by means of an image analysis system. Several DNA, morphometric and textural parameters were evaluated for each patient. The prognostic value of the parameters was investigated by multivariate Cox regression analysis. As prognostic criteria, a distant recurrence-free survival of 5 years and an overall survival of 8 years were considered. In multivariate analyses the anisokaryosis (standard deviation of nuclear radius, Rad-SD) was the strongest parameter in predicting the clinical course of node-negative patients. This was followed by a textural parameter (run-length, NR2 M) and the tumor size (pT). The DNA histogram type could also add prognostic information concerning distant recurrence-free survival, but not overall survival. In both approaches a multivariate prognostic factor was calculated for each of the node-negative patients by a linear combination of the selected variables. Using this factor, patients could be split into 5 subgroups with significantly different risks of distant metastases. Thus, a low-risk subgroup, with a 5-year distant recurrence rate of only 3%, and a subgroup with a considerably higher risk and a distant recurrence rate of 35%, could be distinguished. In survival analysis the low-risk group of node-negative patients showed an 8-year death rate of only 3%, whereas in the high-risk group 30% of the patients had died at 8 years. Thus DNA, morphometric and textural parameters can provide powerful prognostic information in node-negative breast carcinomas. The multivariate combination of the relevant variables may allow a better selection of those node-negative patients with a proven good prognosis, and of those who are at risk of distant recurrence and therefore may benefit from adjuvant treatment.

Adult↗
PubMed1995

Identification of a low-risk group of stage I breast cancer patients by cytometrically assessed DNA and nuclear texture parameters.

Image cytometrical measurements were performed on Feulgen-stained cells from 329 stage I breast cancers (pT1pN0,M0,R0). For each patient, several DNA (ploidy, S-phase fraction, exceeding rates, 2c deviation index, ploidy balance, entropy, and histogram typing), morphometric (area and radius of nuclei), and textural parameters (mainly co-occurrence and run-length) were calculated. The prognostic value of these parameters was investigated by multivariate Cox regression analysis, considering a distant recurrence-free survival of 8 years as the prognostic criterion. In the multivariate analysis, one DNA parameter (histogram type) and two textural parameters (co-occurrence and variation of the average heterochromatin area) were proven to have independent prognostic value. Using a linear combination of these variables, a prognostic factor was calculated for each individual patient. Patients were stratified using this factor into several groups according to their risk for distant recurrence. Thus, a low-risk group of stage I patients was identified, remaining distant recurrence-free for 8 years. In addition, a group of patients with a worse prognosis and an 8-year recurrence rate of about 26 per cent was identified, compared with the average distant recurrence rate of all stage I patients of 13 per cent. A combination of DNA and textural parameters can provide powerful prognostic information in stage I breast carcinomas and may allow a better selection of patients for different therapy protocols.

Adult↗
PubMed1995

Improved prognostication in small (pT1) breast cancers by image cytometry.

Feulgen-stained samples from 460 small (pT1) primary breast cancers were investigated by means of an image analysis system. Several DNA, morphometrical and textural parameters were evaluated for each patient, and the prognostic meaning of these parameters was then investigated by the Cox regression analysis. As prognostic criterion a distant recurrence-free survival of five years was considered. All investigated DNA- and morphometrical parameters as well as several textural parameters showed a significant univariate correlation with the clinical course. In a multivariate approach the axillary nodal status was the most important prognostic parameter, followed by a morphometric parameter (anisokaryosis) and two textural parameters (runlength and co-occurrence). None of the DNA histogram derived parameters could add prognostic information in this multivariate approach. By the linear combination of the four selected variables, an individual prognostic factor was calculated. Using this factor the patients could be split into several groups according to their risk for distant metastases. Thus a low risk group of pT1 patients could be identified with a distant recurrence rate of only 2% after 5 years, and also a group of patients with a considerably worse prognosis and a 5-year distant recurrence rate of 53%. In contrast, using the nodal status as single parameter allows the identification of a low risk group of patients (pN0pT1) with a distant recurrence rate of 10.6%. Therefore, morphometrical and textural parameters can provide powerful prognostic information in small breast carcinomas and may allow a better selection of patients for adjuvant therapy.

Aged↗
PubMed1995

Disease-free survival of node-positive breast cancer patients. Improved prognostication by cytometrical parameters.

Feulgen stained cytologic samples from 225 node-positive breast cancers were investigated by means of an image analysis system. From each tumor sample, 100 cells were scanned and several DNA, morphometrical and textural parameters were evaluated. The meaning of the cytometric parameters for prediction of distant metastases within five years was investigated by the stepwise Cox regression analysis. Most of the investigated DNA- and morphometrical parameters, as well as one textural feature, showed a significant univariate correlation with the clinical course. In the multivariate approach, the lymph node status (pN) was the strongest prognostic factor, followed by the histogram type, the tumor size (pT) and a textural parameter (heterochromatin area). By the linear combination of these selected variables a multivariate prognostic factor was calculated for each individual patient. Using this factor, the patients could be splitted into four groups according to their risk for distant metastases. For this, the continuous range of the multivariate factor was subdivided so that about 35% of the patients were in the middle groups and about 15% of the patients in each of the border groups with highest and lowest factors, respectively. Thus a low risk group (lowest factors) of node-positive patients could be identified with a 5-year distant recurrence-rate of only 6.5%, as well as a group of patients with a considerably worse prognosis (highest factors) and a distant recurrence-rate of 67%. Therefore, DNA, morphometrical and textural parameters can provide powerful prognostic information in node-positive breast carcinomas. Using the multivariate combination of clinical and relevant cytometrical parameters may allow a more appropriate selection of patients for adjuvant therapy.

Biopsy, Needle↗
PubMed1994

Nucleolus organizer regions (AgNORs) in ductal mammary carcinoma. Comparison with classifications and prognosis.

The relevance of silver-stained NORs for classifications and prognosis was investigated in breast tissue. Paraffin sections from 137 cases of invasive ductal breast carcinomas and 12 cases with non-tumorous ductus epithelium as controls were stained according to a modified technique and analysed. From the cancer cases follow-up data up to 10 years (45 to 165 months) and in addition clinical, histological and several DNA distribution parameters were available. The nuclei and the silver grains were measured by means of a semiautomatic image analysis system. Significant differences in AgNOR features were found between controls and diploid tumors (p < or = 0.001), diploid and aneuploid tumors (p < or = 0.001), Bloom-Richardson-gradings I, II, and III (p < or = 0.001), and between the tumor cells from patients developing metastases within 5 years and those without (p < or = 0.002). The prognostic significance of AgNORs was estimated using Cox regression analysis. Four AgNOR features were correlated significantly with survival time. In a multivariate approach offering all parameters available an AgNOR parameter (CV of relative area AgNORs) ranked at the third position beyond the SD of DNA distribution and pTNM-staging. Considering the metastases-free interval of patients the same AgNOR feature showed an independent prognostic validity.

Adult↗
PubMed1994

[Problems concerning standardization and quality assurance in DNA cytometry].

Rat liver imprints were treated with five different fixation techniques. Chicken erythrocytes stored over an extended period in the refrigerator were dropped on each slide before Feulgen staining. By means of an image analysis system chicken erythrocytes, rat leukocytes and hepatocytes were measured and the integrated optical density (IOD) was calculated for each nucleus. The coefficient of variation (CV) of IOD was about 15% for chicken erythrocytes. Leukocytes showed a CV of up to 10%. The CV was lower for hepatocytes than for leukocytes, and lowest for air-dried hepatocytes. The standard error of the mean (SEM) did not show remarkable differences between the fixation groups. For hepatocytes it was in general less than 1% of the respective mean value. The hepatocytes showed a linear staining except the wet formalin-fixed cells. This holds also for the wet formalin fixed leukocytes which showed only 85% of the IOD of 2c hepatocytes. The ratios of erythrocytes to 2c hepatocytes varied between 0.33 and 0.35. The IOD ratios of standard cells to 2c hepatocytes from single specimens showed remarkable differences from the above mentioned ratios of the pooled slides of a fixation group. The use of external standard cells was proved to be problematic, especially because of their variation in staining intensity independent of the staining intensity of hepatocytes.

Animals↗
PubMed1994

[Prognostic value of AgNORs in breast cancer].

Silver stained AgNORs were investigated by means of a semiautomatic image analysis system. Paraffin sections from 137 invasive ductal carcinomas of the breast were available with clinical and histological data, several DNA distribution parameters, and follow-up data of about 10 years (45 to 165 months). By means of the Chi 2-test the correlation of AgNOR features with the other variables was investigated. A significant correlation was found between AgNORs and the histological grading, and between AgNORs and most of the DNA parameters. Tumor size (pT) and pTNM-stage showed significant correlation with one of the AgNOR parameters: standard deviation (SD) of average AgNOR area and of AgNOR number, respectively. No correlation was found between AgNORs and the axillary nodal status (pN). The prognostic significance of AgNORs was estimated by using Cox regression analysis. In a multivariate approach offering all parameters available one AgNOR feature (coefficient of variation of relative AgNOR area) ranked at the third position beyond the SD of DNA distribution and the pTNM-staging. Considering the distant-recurrence free interval of patients instead of the survival time the same AgNOR feature showed an independent prognostic value.

Breast Neoplasms↗
PubMed1994

Prognostic value of quantitatively measured AgNORs in ductal mammary carcinoma.

Argyrophilic proteins of nucleolar organizer regions (AgNOR proteins) were stained by a modified silver staining technique. Paraffin sections from 137 cases of invasive ductal carcinoma of the breast were investigated. The nuclei and AgNOR dots were quantitatively measured by means of a semiautomatic image analysis system. Follow-up data for about 120 months (mean, 102 +/- 47) and clinical/histologic and DNA distribution parameters were available for all patients. The prognostic significance of AgNOR parameters was tested by Cox regression analysis. Four AgNOR features showed a significant univariate correlation with survival time. In multivariate analysis offering all the available parameters, one AgNOR parameter (coefficient of variation of relative AgNOR area) ranked at the third position beyond the standard deviation of DNA distribution and pTNM/staging. When considering the distant recurrence-free survival of patients, the same AgNOR feature provided significant additional prognostic information. Performing survival analysis for the prognostically defined subgroup of pTNM/stage I patients and offering all DNA and AgNOR features the same AgNOR parameter yielded the highest prognostic validity. These results show that quantitatively measured AgNORs yield prognostic factors in breast cancer.

Breast Neoplasms↗
PubMed1994

Problems concerning the quality of DNA measurements on Feulgen-stained imprints. A study of five fixation techniques.

Feulgen-stained rat liver imprints were investigated, and hepatocytes, lymphocytes and granulocytes were measured. Additionally, chicken erythrocytes placed on the slides were measured as an external DNA standard. The imprints were treated according to five different fixation protocols. The measured integrated optical density (IOD) was normalized according to the leukocytes and afterwards scaled according to the diploid hepatocytes. The mean IOD, coefficient of variation (CV), standard error of the mean (SEM) and IOD ratios of distinct cell groups were calculated. The CV of the IOD for hepatocytes was slightly better for air-dried preparations. It was larger for leukocytes than for hepatocytes and worst for chicken erythrocytes. The SEM of hepatocytes did not show remarkable differences between the fixation groups; in general it was near 1%. In all cases the IOD ratios of 2c, 4c and 8c hepatocytes reasonably well followed the expected ratio of 1:2:4 except for wet, formalin-fixed hepatocytes (3.8). The ratios of leukocytes to 2c hepatocytes were about 1.0 for air-dried preparations but considerably lower (0.85) for wet fixation in formalin. The IOD ratios of chicken erythrocytes to 2C hepatocytes varied from 0.33 to 0.35. The deviation of the ratios of single specimens from the estimated mean of a fixation group are described.

Animals↗
PubMed1994

Malignancy associated changes in squamous epithelium of the head and neck region.

Subtle cellular changes are known to exist in normal host tissue adjacent to tumours. These are called malignancy associated changes (MAC). To get more insight into the degree of expression and local spread of such changes we performed high resolution image cytometry on visually normal intermediate cell nuclei in smears from patients with laryngeal or pharyngeal squamous cancer. The smears were taken from the tumour surface, from a border region of the tumour and from a distant unsuspicious buccal site. In addition buccal smears from healthy control persons were examined. In a pilot study smears from 12 cancer patients and 11 control persons and in a succeeding validation study 63 controls, 18 non-tumour patients and 25 cancer patients were investigated. In both studies the occurrence of MACs was demonstrated quantitatively. In cancer patients normal appearing intermediate cells from the three different sampling sites could be discriminated with 65% in the pilot study and with 53% correct classification in the validation study. In addition the influences of smoking behaviour and sex were investigated in the control group. Only in the latter case there was a significant difference between female and male with a 63% correct cell and 71% correct specimen classification.

Carcinoma, Squamous Cell↗
PubMed1994

Biological monitoring of chemical exposure in nickel workers by imaging cytometry (ICM) of nasal smears.

Highly sensitive and inexpensive methods that are not time consuming are desirable for monitoring the workplace environment for the detection of cytotoxic hazards, particularly cancerous risks. It is possible to detect precancerous and cancerous lesions in samples taken by brushing the nose, but the cytological diagnoses can be affected by an inability to obtain representative smears from the sometimes very small focal lesions, and uncertainties in the subjective interpretation of suspicious cells when these are small in number. In an attempt to improve diagnosis we applied imaging cytometry (ICM) and tested the concept of malignancy-associated changes (MAC) in routinely Papanicolaou-stained smears. Cells of non-goblet type that visually appeared normal were selected from nickel workers with and without dysplastic lesions of the nasal mucosa. A set of nuclear features was measured by ICM and used for discriminant analysis. We were able to differentiate between workers with non-dysplastic normal and suspicious mucosa smears and those with dysplastic lesions. Unexpectedly, it was found possible to distinguish between workers in the roasting/smelting and the electrolysis departments, who were exposed to different carcinogenic nickel compounds. A further surprising finding was the possibility to distinguish smokers and non-smokers among the nickel workers.

Adult↗
PubMed1992

Interactive cytometry, chance or evil of bias?

Interactive selection of a limited number of cells in imaging cytometry for determining the DNA histogram of breast cancer cells as the best known prognosticator at the moment, implies statistical and systematic sampling problems. Analysis of histograms of 361 breast cancer aspirate specimens measured in two laboratories demonstrate the expected high statistical variations in view of the only 100 cells measured per case but also slight systematic differences. Controlled systematic sampling without pathological bias results in a somewhat higher malignancy grading than selective biased sampling. For this finding we have no explanation. The main result is, however, that we did not find the expected contrary which makes the argument for at least this application invalid that expert pathologists are needed for reliable interactive sampling.

Adenocarcinoma↗
PubMed1992

Cytometry in histological sections of colon carcinoma.

A short description of a project of cytometry in histological sections of colon carcinoma is given with emphasis on the methodical aspects. Possible strategies of cytometric measurement and problems related to it (focus, overlap, segmentation of objects) are described. The main effort concerns interactive selection of tumor cells and the segmentation in cases of densely distributed and overlapping nuclei. All other succeeding processing steps are performed fully automatically. The resulting quantitative features are stored together with the original images on an optical disk for further examinations and reexaminations, allowing the direct relation of feature values to visual image content. The evaluation of the features as well as their interpretation is only at the beginning. Especially the problem of relating section information with true 3-dimensional information is not described here and necessitates further research. In a first investigation only a few tumors without and with metastases were analyzed. The preliminary results correspond with findings of Kunze et al.

Cell Nucleus↗
PubMed1990

Quantitative evaluation of radiation-induced changes in sperm morphology and chromatin distribution.

Sperm head cytometry provides a useful assay for the detection of radiation-induced damage in mouse germ cells. Exposure of the gonads to radiation is known to lead to an increase of diploid and higher polyploid sperm and of sperm with head shape abnormalities. In the pilot studies reported here quantitative analysis of the total DNA content, the morphology, and the chromatin distribution of mouse sperm was performed. The goal was to evaluate the discriminative power of features derived by high resolution image cytometry in distinguishing sperm of control and irradiated mice. Our results suggest that besides the induction of the above mentioned variations in DNA content and shape of sperm head, changes of the nonhomogeneous chromatin distribution within the sperm may also be used to quantify the radiation effect on sperm cells. Whereas the chromatin distribution features show larger variations for sperm 21 days after exposure (dpr), the shape parameters seem to be more important to discriminate sperm 35 dpr. This may be explained by differentiation processes, which take place in different stages during mouse spermatogenesis.

Animals↗
PubMed1989

Computer-assisted imaging cytometry of nuclear chromatin reveals bone tumor virus infection and neoplastic transformation of adherent osteoblast-like cells.

Established osteoblast-like (OB) cells infected with the bone tumor-inducing C-type retrovirus OA MuLV remained nontumorigenic over 104 cell culture passages. DNA histograms revealed a new cell population with a stem line peak at 5c. A second OA MuLV-infected OB cell line underwent neoplastic transformation with increasing passage level. These cells showed diffuse aneuploidy. Stepwise linear discriminant analysis of the chromatin structure of control, OA MuLV-infected, and FBR osteosarcoma virus-transformed cell lines resulted in various levels of discrimination ranging between 79.6% for control cells versus nontumorigenic OA MuLV-infected cells, and 96.6% for nontumorigenic OA MuLV-infected cells versus FBR osteosarcoma virus-transformed cells. OA MuLV-infected tumorigenic cells and FBR osteosarcoma virus-transformed cells were discriminated at a 93.6% level.

Animals↗
PubMedDate not supplied

Interphase cytogenetics in pathology: principles, methods, and applications of fluorescence in situ hybridization (FISH).

Characteristic chromosome aberrations have been identified in various tumors. Fluorescence in situ hybridization (FISH) using specific probes that are generated by vector cloning or in vitro amplification and labeled with fluorescent dyes allow for the detection of these genetic changes in interphase cells. This technique, that is also referred to as "interphase cytogenetics", can be performed in cytological preparations as well as in sections of routinely formaldehyde-fixed and paraffin-embedded tissue. In cancer research and diagnostics, interphase cytogenetics by FISH is used to detect numerical chromosome changes and structural aberrations, e.g., translocations, deletions, or amplifications. In this technical overview, we explain the principles of the FISH method and provide protocols for FISH in cytological preparations and paraffin sections. Moreover, possible applications of FISH are discussed.

Cytological Techniques↗