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Biomedical subjects

G Auer

Publications and source records attributed to G Auer.

At least 109 records · Page 6Linked to original sources
PubMed1993

DNA pattern and dietary habits in patients with breast cancer.

An association between dietary fat, micronutrients and breast cancer aetiology and prognosis has been found in studies of experimental animals and in epidemiological studies. The relationship between dietary habits and the nuclear DNA content of breast cancer cells was studied in 82 women aged 50-65 years. A dietary history interview was conducted within 4 months following surgery. Patients having tumours with euploid DNA pattern reported lower mean intake of saturated fatty acids (FA) in absolute terms, lower mean intake of total fat, saturated FA, and monounsaturated FA, in percentage of total energy intake (E%), a higher E% from protein, and a higher intake of vitamin D, and selenium per 10 MJ than did patients having tumours with aneuploid DNA pattern. In the stepwise logistic regression analysis, the multivariate odds ratios (OR) for having a tumour with aneuploid DNA pattern was 1.16 (95% confidence interval, 1.04-1.28) for each 1 g increase in intake of total fat (E%) and 0.95 (95% confidence interval, 0.92-0.99) for each mg increase in selenium intake per 10 MJ. When total fat was substituted with types of fat, the OR for having a tumour with aneuploid DNA pattern was 1.30 (95% confidence interval, 1.07-1.59) for each 1 g increase in intake of saturated FA (E%). These results suggest a correlation between a diet rich in fat and protein and the DNA content of breast cancer cells.

Aged↗
PubMed1993

Proliferating cell nuclear antigen (PCNA) expression and nuclear DNA content in predicting recurrence after radiotherapy of early glottic cancer.

Proliferating cell nuclear antigen (PCNA) is a DNA replication protein maximally elevated in late G1 and S phases of the cell cycle. By using monoclonal antibodies, the expression of PCNA can be quantified and the rate of tumour cell proliferation estimated. The degree of DNA aberration in a tumour cell population reflects its genetic instability and has been implicated as a prognostic factor in an increasing number of solid tumours. The nuclear DNA content can be assessed by densitometric image cytometry DNA analysis. Both PCNA and DNA analysis can be performed on histological sections from paraffin embedded biopsies. In search of efficient and reproducible methods to identify early glottic cancers with increased risk for recurrence after radiotherapy, the PCNA expression as well as the DNA content of the diagnostic biopsies from 28 T1N0M0 glottic cancers were assessed. The group of tumours which recurred locally after radiotherapy displayed lower PCNA expression and higher DNA aberration than the group of tumours which were cured. Moreover, a combination of both parameters improved the possibility to discriminate the two groups. For T1 glottic cancer displaying high grade of genetic instability or low grade of proliferation, treatment regimes other than radiotherapy and closer follow-ups could be considered.

Adult↗
PubMed1993

DNA image analysis in childhood acute lymphoblastic leukemia.

DNA index (DI) and percentages of cells in S and G2/M phase were determined in Feulgen stained nuclei of blasts from 31 cases of childhood ALL at diagnosis. In 6 cases the results of DNA analysis and cytogenetics were concordant showing hyperdiploidy. Two other cases with normal karyotype were revealed as DNA aneuploid with image analysis. Cases with cytogenetic abnormalities like translocation, deletion or presence of single or double supernumerary chromosomes had DI within normal ranges. Nine ALL cases (29%) were found to be DNA aneuploid--8 hyperdiploid and 1 hypodiploid. The percentages of cells in S and G2/M phase for blasts from bone marrow (mean 17.6%) were significantly higher than those estimated in the peripheral blood (mean 1.57%). We conclude that analysis by image cytometry can detect aneuploid DNA content even in cases, which showed a normal karyotype and provides new information concerning the biological aspects of leukemic blasts.

Adolescent↗
PubMed1993

Polyploidization by means of endoduplication in a human breast cancer cell line.

Near DNA diploid human adult solid tumors are often associated with certain near-tetraploid cells. In an established human breast cancer cell line, Hs578T, with a DNA index in the hyperdiploid region, polyploid cells appeared during exponential growth. Among clones generated from single cells and analyzed by the video time lapse technique, an intraclonal interdivision time (IDT) heterogeneity is presented that renders endoduplication a plausible explanation for the generation of the polyploid cells observed. This conclusion, drawn from our IDT analysis, is supported by curves drawn from counting grain-positive cells during continuous labeling with [3H]-thymidine. Our results are compared with a parallel analysis of the aneuploid human breast cancer cell line MDA-231, generating intraclonal IDT heterogeneity, due mainly to the mitotic instability of that line, as we reported previously.

Breast Neoplasms↗
PubMed1993

Methodological aspects of DNA image cytometry in normal bone marrow smears.

The possibility of using DNA image cytometry in hematological material was evaluated in 27 Feulgen stained normal bone marrow smears. The 95% normal limits of DNA index (DI) determined separately for each cell population in bone marrow were 0.89-1.15, 0.93-1.09 and 0.92-1.12 for blasts, granulocytes and lymphocytes, respectively. The mean DI for blasts, granulocytes and lymphocytes was 1.02, 1.01 and 1.02, respectively. In the blasts population the mean percentage of cells in S+G2/M phase was 38.1% (S.D. 12.9%, range 14.3-65.6%), whereas the corresponding values for granulocytes and lymphocytes were below 1%. Calculation of DI and G0/G1 C.V. obtained in bone marrow smears subjected to Feulgen hydrolysis (5 N HCl, 22 degrees C) for different periods of time revealed the presence of a plateau of results between 60 and 120 min for all of the cell types. The intraobserver and interobserver reproducibility was confirmed by duplicate measurements of each subpopulation (P > 0.05). A comparison of DI and G0/G1 C.V. using smears from the same donors stained with the Feulgen method either straight away or after destaining from May-Grunwald-Giemsa confirmed that destained smears can be used, provided applying appropriately prepared reference cells. We conclude that image cytometry can be used reliably to analyze DNA content in hematological material.

Adolescent↗
PubMed1992

Elevated stromelysin-1 and reduced collagenase-IV expression in invasive rat embryo fibroblasts expressing E1A deletion mutants + T24-H-ras.

We have studied the in vitro invasive properties of 3 cell lines derived from the co-transfection of rat embryo fibroblasts (REF) with EIA genes deficient in exon 2 and T24-ras. All 3 cell lines showed invasive properties at passage 10 after isolation. Invasive cells expressed elevated levels of stromelysin-1 and reduced levels of 68-kDa type-IV collagenase compared with untransfected REF. In 2 cell lines the invasive capacity increased during in vitro propagation. The expression of stromelysin-1 increased during this process, whereas 68-kDa type-IV collagenase was persistently expressed at reduced levels. In the third clone analyzed, the invasive capacity decreased during culture, in parallel with decreased expression of stromelysin-1. The low level of stromelysin-1 expression observed in this cell line did not result from loss of AP-1-transcription-factor activity, and was not reversed by phorbol-ester treatment.

Adenovirus Early Proteins↗
PubMed1992

Immunoreactivity with monoclonal antibody A-80 and nuclear DNA content in benign and malignant human breast disease.

Immunohistochemical analysis with the monoclonal antibody (MoAb) A-80, recognizing a tumor-associated cytoplasmic mucin-type glycoprotein, and cytometric nuclear DNA assessment were performed on 314 surgical specimens of the human mammary gland. The series included 36 benign conditions, 34 epithelial hyperplasias, 40 carcinomas in situ, and 204 primary invasive carcinomas. Normal breast parenchyma, benign tumors, and other nonmalignant lesions were all of DNA diploid (euploid) type and rarely expressed the A-80 glycoprotein. Differences in MoAb A-80 immunoreactivity and nuclear DNA content were noted among subtypes of epithelial hyperplasias. Fifteen of 34 epithelial hyperplasias were of DNA aneuploid type and the majority were A-80 immunoreactive. Of these 15 immunoreactive aneuploid epithelial hyperplasias, atypical intraductal hyperplasia was the most common subgroup. None of the 19 epithelial hyperplasias of DNA euploid type immunoreacted. Most of the intraductal (33 of 40) and invasive (180 of 204) carcinomas immunostained with MoAb A-80. The majority of the A-80 immunoreactive malignant tumors were of DNA aneuploid type (26 of 33 carcinomas in situ and 108 of 180 invasive mammary carcinomas). The results suggest that expression of the A-80 glycoprotein occurs at an early stage of malignant transformation. Genetically stable (euploid) mammary tumors seem to immunoreact with MoAb A-80 less frequently than genetically unstable (aneuploid) tumor variants. Combined analysis with MoAb A-80 and of nuclear DNA content in premalignant and malignant mammary lesions could be a useful tool of differential diagnostic and prognostic value.

Antibodies, Monoclonal↗
PubMed1992

The prognostic value of cytometric DNA analysis in early stage tongue cancer.

In spite of a small size and seemingly localised properties T1 tongue cancer does recur after surgical treatment, locally and/or in regional lymph-nodes, in 30-40% of the patients, and 50% of patients with recurrent disease die because of their cancer. If these patients could be identified by analysis of relevant parameters on the primary biopsy reflecting the biological properties of the tumours more extensive treatment regimes could be given selectively. In 47 primary biopsy specimens from patients with T1N0M0 squamous cell carcinoma of the mobile tongue the aberration in cellular DNA content was significantly higher in the group of tumours which recurred after surgical treatment compared with the non-recurrent group. Tumours in females recurred more frequently than in males. No significant correlation between recurrence and grade of histological differentiation or tumour thickness could be found. Image cytometry DNA analysis provides an objective and reproducible assessment of the nuclear DNA content which could facilitate selection of adequate treatment strategies.

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

Histopathologic and cytochemical characteristics of interval breast carcinomas from the Stockholm Mammography Screening Project.

Combined morphological and cytochemical malignancy grading in addition to tumor stage was applied to assess the malignant potential of so-called interval carcinomas from the Stockholm randomized mammography screening study. Only interval carcinomas surfacing within two years from screening were included. Fifty-four percent of the tumors were in stage I and 46% of the carcinomas eligible for DNA analysis were diploid, i.e. low-malignant. An overrepresentation of prognostically unfavorable tumor characteristics was found only within the subgroup 'true' and 'early' interval cancer.

Adult↗
PubMed1992

Nuclear protein content and Ki-67 immunoreactivity in nonneoplastic and neoplastic thyroid cells.

The nuclear DNA content in thyroid tumor cells has been shown to be closely related to the malignant potential of the neoplasm. Besides DNA, nuclear protein (NP) constitutes the major mass of the nucleus. The NP content may vary significantly in relation to the proliferative stage in growing as compared to growth-arrested cells. The increase in NP content associated with the transition from G0 to G1 occurs before the onset of DNA synthesis and may be used to assess growth activity. The nuclear DNA and NP contents were analyzed in 90 nonneoplastic lesions and 75 benign and 62 malignant thyroid tumors. All nonneoplastic specimens were euploid, and 1 of 90 was growth activated. In the group of benign tumors, 59 were euploid, and 16 were aneuploid. Among these there were 5 (9%) of 59 and 6 (38%) of 16 growth-activated specimens, respectively. In the group of malignant tumors 57 of 62 were classified as euploid, and in this group 12 (21%) showed growth activity according to the NP content. Five of 62 were aneuploid, and 3 (60%) of these 5 tumors were growth activated. Evaluation of the growth activity by means of monoclonal antibody Ki-67 was performed on a subgroup of 32 thyroid specimens, both nonneoplastic and neoplastic lesions. Ki-67 immunoreactivity was observed in 0-1.1% cells of 6 nonneoplastic lesions, in 0-3.1% cells of 14 benign cells and in 0.2-3.9% cells of 12 malignant thyroid tumors. Growth activity, as reflected by the NP/DNA ratio and Ki-67 immunoreactivity, appears to be low both in nonneoplastic thyroid lesions and thyroid tumors.

Adenoma↗
PubMed1992

Addition of nuclear DNA content to the AMES risk-group classification for papillary thyroid cancer.

BACKGROUND: The purpose of this study was to prospectively assess whether nuclear DNA content added prognostic value to existing risk factors in patients with papillary thyroid cancer. METHODS: Nuclear DNA content was measured both on the fine needle aspiration material and the surgical specimen in 73 patients with primary or recurrent papillary thyroid cancer. We modified the existing age of patient, presence of distant metastases, extent and size of the tumor (AMES) risk-group classification to include DNA ploidy with AMES (DAMES). Patients with euploid tumors that were AMES low risk were considered to be DAMES low risk; patients with euploid tumors that were AMES high risk became intermediate risk, and patients with aneuploid tumors that were AMES high risk became DAMES high risk. RESULTS: Forty-eight patients were in the DAMES low-risk group. Recurrences and/or distant metastases developed in only four (8%) of these patients. Twenty-two patients were in the DAMES intermediate-risk group. Twelve (55%) of the intermediate-risk group had residual, recurrent, or distant metastatic disease, with one death from cancer at 120 months. Three patients were in the DAMES high-risk group. Distant metastases developed in all three patients, who died within 24 months from thyroid cancer. A statistically significant difference existed in the development of recurrence/metastases or death from cancer in the DAMES high-risk group compared with the other risk groups combined. CONCLUSIONS: Nuclear DNA content adds prognostic value to the existing AMES risk-group classification. Because DNA analysis on fine needle aspiration correlated well with the surgical specimen DNA analysis, this modified classification can be used perioperatively to further individualize the treatment of patients with papillary thyroid cancer.

Adult↗
PubMed1992

The DNA profile of breast cancer in situ.

The nuclear DNA content of 46 mammary adenocarcinomas in situ was measured by means of image cytometry in 4-microns-thick Feulgen-stained histological sections. Aneuploidy was found in 23 cases (50%), whereas the other 23 cases exhibited a diploid DNA distribution pattern. Intraductal carcinoma, the most common subtype in the present study, was found to be aneuploid in 19 cases (63%), with the comedo variant showing aneuploidy in as many as 10 of 11 cases (91%). In contrast, lobular and papillary carcinoma in situ exhibited only 17% and 0% aneuploidy, respectively. The percentages of aneuploid and diploid DNA profiles of the in situ lesions in the present study are almost identical to those observed in invasive breast adenocarcinoma. This indicates that the DNA distribution pattern characteristic for an individual breast adenocarcinoma is already established at the in situ stage, i.e., it occurs before invasiveness and does not progress from a euploid to an aneuploid pattern. In clinical routines DNA ploidy measurements may be of help to distinguish between e.g., hyperplasias and in situ lesions and may also indicate in which direction the malignancy potential of in situ lesions will develop.

Adult↗
PubMed1991

Analysis of the DNA content in the management of thyroid tumours.

Thyroid carcinoma is rare and constitutes about 1% of all malignant tumours. For some time it has been known that age, sex, histology, and tumour grade are factors of importance for prognosis. In Stockholm we have analyzed the amount of nuclear DNA in thyroid tumours for the last 10 years. In our studies and those of other nuclear DNA-analysis has given important prognostic information for differentiated thyroid tumours in addition to that provided by histopathology, and may be of value preoperatively for treatment planning. DNA-analysis is well established in our clinical work and is one of the factors considered in a prospective randomized study concerning patients with papillary carcinoma in the Stockholm-Uppsala area. Tumours with diploid nuclear DNA pattern are randomized between lobectomy and total thyroidectomy in this study.

Aneuploidy↗
PubMed1991

Nuclear DNA analyses in archival material from primary malignant melanoma. A pilot study.

In 28 cases of malignant melanoma, paraffin-embedded specimens were analyzed in order to determine the reliability of ploidy results. The material consisted of thin and thick melanomas. The results indicate that useful prognostic information may be obtained in this kind of material by means of DNA measurements, provided that the analysis is performed on morphologically identified tumor cells. The value of DNA measurements in malignant melanomas may, however, not be as clear as has been reported for several other tumors.

Adolescent↗
PubMed1991

Comparison of nuclear DNA content in primary and metastatic malignant melanoma.

The DNA patterns obtained from 23 primary malignant melanomas and 35 corresponding metastases were compared and found to differ in many cases. In eight cases the primary tumors and their metastases had a ploidy type I ("euploid") DNA pattern. One case had a type I primary tumor and both type I and type II metastases. Five cases had type I primary tumors and ploidy type II ("aneuploid") DNA pattern metastases. In five cases the primary tumors and corresponding metastases were type II, and in another four cases the primary tumors were type II, whereas the metastases were type I. We interpret these data as indicating that malignant melanomas (more often than adenocarcinomas) are composed of genetically heterogeneous tumor sublines that frequently give rise to heterogeneously composed metastases. Since we sometimes observed a change in the DNA content in malignant melanomas, it seems to be more difficult to obtain prognostic information from DNA analysis in malignant melanoma as compared to the more stable adenocarcinomas.

Adult↗
PubMed1990

Nuclear DNA content and survival in medullary thyroid carcinoma. Swedish Medullary Thyroid Cancer Study Group.

In a nationwide study of medullary thyroid carcinoma, the relation between nuclear DNA content and survival was studied in 211 patients with complete follow-up of up to 27 years. Morphologically identified tumor cells were analyzed by an image cytometric method. The DNA histograms were classified (1) by an objective method in which the degree of aneuploidy was defined as the percentage number of tumor cells with DNA values exceeding the 90th percentile of diploid control cells (P90), and (2) according to a subjective evaluation of whether the DNA profiles represented a euploid or an aneuploid DNA pattern. Both classifications separated groups with marked differences (P less than 0.001) in survival. A multivariate proportional hazards analysis indicated that each method provided additional information when the other one was taken into account. In patients whose tumors were classified according to the objective P90 method 1, the relative hazards (with 95% confidence interval) in the groups with P90 values of 36% to 69% and greater than or equal to 70% were 1.6 (0.9-2.8) and 2.1 (1.1-4.0) respectively, compared with the reference group. With the subjective method 2 the corresponding figure for the group with aneuploid tumors was 1.7 (1.0-2.0) compared with the group with euploid tumors.

Adolescent↗