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Biomedical subjects

A Fallenius

Publications and source records attributed to A Fallenius.

11 recordsLinked to original sources
PubMed1992

Image cytometric DNA analysis in human breast cancer analysis may add prognostic information in diploid cases with low S-phase fraction by flow cytometry.

Measurements of DNA ploidy can be performed either with image cytometry (ICM) or flow cytometry (FCM); both methods provide independent prognostic information in primary breast cancer. The aim of the present investigation was to compare the two methods and to relate the findings to prognosis (median follow-up 42 months). Concordance in ploidy status (diploid, tetraploid, aneuploid) was obtained in 76% of the samples (168/222). When the fraction of S-phase cells (SPF) from FCM analysis was also taken into consideration, four different groups of samples were obtained (Flow I-IV), which were considered to correspond to the Auer classification (Auer I-IV) of DNA histograms obtained from image cytometry. Complete concordance between the two techniques now was 70% (155/222). Samples classified as Flow I (diploid or near-diploid with low SPF) and Auer I had a distant metastasis rate of 3/60 (5%), as compared to 62/154 (40%) for all other combinations of the Flow and Auer classifications taken together. Thus, the only findings of prognostic importance were that some samples were Flow I but not Auer I, or vice versa. These two groups represent 17 (7.7%) and 14 (6.3%), respectively, of the total number of samples, and had frequencies of distant metastasis similar to those of the other high-risk groups, namely, 7/17 and 5/14, respectively. In a multivariate analysis, flow cytometric S-phase value was a stronger prognostic factor than either the Flow and Auer classification. We conclude that when routine FCM DNA analysis is used, diploid or near-diploid samples with a low S-phase value should be reanalyzed with ICM.

Breast Neoplasms↗
PubMed1992

Prognostic significance of immunohistochemical c-erbB-2 proto-oncogene expression and nuclear DNA content in human breast cancer.

Immunoreactivity of the c-erbB-2 proto-oncogene product and nuclear DNA content were assessed in specimens from 211 breast cancer patients with a mean follow-up of 16 years (range 13-19 years). A routine immunoperoxidase technique was used and cytometrical DNA assessments were performed on cytodiagnostically identified tumour nuclei, using image analysis. C-erbB-2 cell membrane staining was observed in 29% of the cases and was found to be related to tumour size (P = 0.02), histopathological grade (P = 0.02) and nuclear DNA content (P < 0.01). In univariate analysis immunohistochemical c-erbB-2 expression was of prognostic significance among node-positive patients (P = 0.02), but not among women with node-negative disease. This prognostic ability was reduced by multivariate analysis and was no longer significant. In contrast, nuclear DNA content was significantly related to distant recurrence-free survival even in multivariate analysis after adjustment for nodal status and tumour size (P < 0.01). In conclusion, the findings of the present study indicate that c-erbB-2 expression is of limited prognostic value in a subgroup of patients, whereas nuclear DNA content seems to provide significant prognostic information even in node-negative patients.

Adult↗
PubMed1990

Nuclear DNA content, histological grade, and clinical course in patients with nonpalpable mammographically detected breast adenocarcinomas.

Sixty-five consecutive female patients, age 35-83, with nonpalpable breast carcinomas detected by mammography were classified with both morphological and cytochemical malignancy grading. Cytochemically, the tumors were divided into euploid and aneuploid types indicating low and high malignancy potential, respectively. The mean follow-up time in the euploid group was 6.7 years and in the aneuploid group 8.0 years. No significant difference in mortality was observed in the two groups comprising 65% euploid and 35% aneuploid tumors. Our results here indicate that an early detection of breast cancer at a clinically occult and nonpalpable level leads to better prognosis even in patients with aneuploid tumors whose tumors otherwise are considered to be highly malignant.

Adenocarcinoma↗
PubMed1989

Prognostic value of nuclear DNA content in breast cancer in relation to tumor size, nodal status, and estrogen receptor content.

The prognostic value of nuclear DNA distribution pattern in relation to tumor size, axillary lymph node status, and estrogen receptor (ER) content was studied in 464 patients with primary, operable mammary adenocarcinoma. The median follow-up time was 3 1/2 years. Slide cytophotometric DNA analysis was performed on morphologically identified Feulgen-stained tumor cells. The tumors were classified into four subgroups according to their DNA histogram type. DNA content was significantly related to tumor size and ER level but not to nodal status. When all variables were stimultaneously introduced into Cox's proportional hazards model, tumor size, nodal status, and DNA profile remained as significant predictors of recurrence. Restricting the analysis to node-negative patients, both DNA profile and tumor size showed a significant prognostic value. DNA did not contribute significant prognostic information in node-positive patients. However, the trends in recurrence-free survival were similar to those in the node-negative subgroup: patients with aneuploid tumors tended to fare worse than those with euploid carcinomas.

Biomarkers, Tumor↗
PubMed1987

Two randomised phase II trials of intermittent intravenous versus subcutaneous alpha-2 interferon alone (trial 1) and in combination with 5-fluorouracil (trial 2) in advanced colorectal cancer.

Sixty-five patients with advanced colorectal cancer were randomised to one of two schedules of recombinant alpha-2 interferon (IFN). In the first study, 36 patients received single-agent IFN, either 50 X 10(6) U/m2 intravenously on 5 consecutive days every 4 weeks, or 20 X 10(6) U/m2 subcutaneously three times per week. No tumour responses were seen and toxicity was unacceptable. In the second study, 29 patients received IFN in two similar schedules, but the dose of IFN was reduced to 20 X 10(6) U/m2 per day in the intravenous arm and to 5 X 10(6) U/m2 per day in the subcutaneous arm. In addition these patients were administered intravenous 5-Fluorouracil (5-FU), 250-500 mg/m2 per day on the first 5 days of each 4-weekly cycle. Although the toxicity of this second study was tolerable, only one short-lived partial remission was observed. Alpha-2 interferon, alone or in combination with 5-FU, is ineffective in advanced colorectal cancer.

Adenocarcinoma↗
PubMed1987

Comparison between slide and flow cytophotometric DNA measurements in breast tumors.

Nuclear DNA analysis was performed in 37 human mammary adenocarcinomas in order to elucidate the difficulties and pitfalls connected with the interpretation of DNA histograms obtained using different methodologic approaches. For each tumor, DNA profiles were obtained by means of slide microspectrophotometry on a fine needle aspirate, slide cytophotometry on a 4-micron histologic section and flow cytometry on a suspension prepared from a cube of fresh tissue. When the DNA histograms were interpreted according to criteria usually applied to discriminate low-grade malignant tumors from high-grade malignant tumors, some tumors classified as euploid by one method were classified as aneuploid by another method. The main reasons for this weak correlation seem to be in specimen preparation and in tumor cell representation within the specimen between the methods. Another reason is that slide and flow techniques exhibit different sensitivities for malignancy-associated nuclear DNA changes: minor alterations of the DNA content of the tumor stemlines seem to be more exactly reported by means of the flow technique whereas structural alterations of the nuclear chromatin seem to be more sensitively recorded by means of the slide technique. It is suggested that thorough control of each step of the various DNA analysis procedures and the use of information obtainable by slide and flow techniques taken together may significantly improve the prognostic value of DNA measurements.

Adenocarcinoma↗
PubMed1986

Prognostic significance of nuclear DNA analysis in histological sections in mammary carcinoma.

The nuclear DNA content in tumor cells from invasive ductal breast carcinomas was analyzed in 26 patients who survived more than 10 years and in 23 patients who died within 2 years after operation. The DNA content of individual tumor cells was measured in sections from the originally paraffin-embedded specimens. In short-term survivors, a large proportion of cells with very high DNA values was found in all tumors except one. Only two patients of the long-term survivors had tumors that exhibited such high DNA values. Prognostic information obtained by DNA analysis compared with histologic malignancy grading showed that the specificity using DNA analysis was distinctly higher. The data thus suggest that analysis of DNA content of tumor cells in breast adenocarcinomas can be a useful supplement to histologic malignancy grading to obtain prognostic guidance in individual patients.

Adenocarcinoma↗
PubMed1986

Nuclear DNA content in mammary carcinomas in women aged 35 or younger.

Nuclear DNA content was studied in cytologic preparations obtained from 50 patients aged 35 or less with primary mammary carcinoma. As many as 90% of the tumors were aneuploid, i.e., exhibited DNA profile types III and IV. The cytologic diagnosis was confirmed by histologic examination in 46 patients. The majority of these tumors, 83%, were invasive ductal carcinomas, while medullary carcinomas constituted 13% of the surgical material. As judged from their DNA profiles, most mammary carcinomas in this age group would be tumors of high malignancy potential. This does not seem, however, to influence the prognosis of young women with breast cancer as much as would be expected, possibly because of a better-functioning immune surveillance system in this age group.

Adult↗
PubMed1983

Cytochemical changes in the nucleus during tumour development.

The general background to tumour analytic work using quantitative optical cytochemical methods is first presented. An instrument complex, constructed especially for multiparameter work in cytopathological material has been developed. Nuclear changes have been followed in cell populations during their development through different grades of atypia to cancer and conspicuous cytochemical changes were observed. In a comprehensive series of clinically verified mammary carcinomas, a large percentage of cases was found in which the DNA values were within the normal range, while the others showed pronounced aneuploidy. A clear correlation was found between DNA profile-type and patient survival, the latter of which reflects the degree of malignancy in the individual case. The shift from resting state (G0) to growth activated G1-stage is initiated by a large increase of the nuclear proteins. Mammary tumours of a high malignancy grade, as judged by their DNA profile type, showed an especially great accumulation of nuclear protein and thus a high degree of activation. DNA-profile measurements, preferably combined with determinations of nuclear proteins can thus be used for judging malignancy grades in mammary tumours, which is also of considerable clinical interest. An as yet limited observational material also indicates similar situations in some other types of tumour.

Animals↗
PubMed1983

Cytochemical classification of nonpalpable breast carcinoma.

A stereotaxic needle biopsy technique makes it possible to obtain diagnostic cytologic material from nonpalpable breast lesions down to sizes of 2 to 3 mm in diameter. Considering the high correlation between the type of DNA distribution pattern and patient survival demonstrated in palpable breast carcinomas, cytophotometric DNA measurements were performed on smear preparations from nonpalpable tumors. In a series of 30 consecutive nonpalpable breast carcinomas, the same types of DNA profiles as shown in palpable tumors were found. This indicates that malignancy grading of breast carcinomas by cytochemical means can be performed on stereotaxic needle biopsy material and that an improved prognostic evaluation may be expected by the use of the methods described. This should result in a better therapeutic approach to patients with nonpalpable breast tumors.

Adult↗