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  • 1
    ISSN: 1432-2307
    Keywords: Thyroid disease ; Feulgen-DNA ; Scanning microdensitometry ; Autoradiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Nuclear enlargement in hyperfunctioning thyroid lesions which has been found in earlier cytophotometric studies is also one of the criteria in the subjective histological estimation of thyroid function. Histopathological assessment is, however, often unreliable. In the present study stage scanning cytophotometric measurements in Feulgen-stained tissue sections were used to determine the nuclear changes encountered in non-toxic and toxic nodular goitre, and in toxic diffuse goitre. To ensure optimal selection of specimens for measurements autoradiography was used. Specimens of toxic diffuse goitre invariably had enlarged nuclei, but no difference was found between nodules in non-toxic and toxic nodular goitre. In fact, the same nuclear area was found in hot nodules, warm nodules and perinodular tissue in non-toxic nodular goitre, and in hot nodules in toxic nodular goitre. Thus there are lesions with clear-cut clinical, biochemical, and autoradiographic hyperfunction that do not have enlarged nuclei. Against this background it is possible that the nuclear enlargement present in toxic diffuse goitre reflects the disorder in itself and not the hyperfunctioning state. Hyperdiploid cell nuclei were found in all cases of toxic diffuse goitre and in a higher precentage than in the other lesions. It was not possible to distinguish nontoxic and toxic nodular goitre on this basis.
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  • 2
    ISSN: 1432-2307
    Keywords: p53 protein ; DNA ploidy ; Colorectal cancer ; Immunohistochemistry ; Flow cytometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract p53 expression, DNA ploidy and S-phase fraction were analysed retrospectively in colorectal adenocarcinomas from 293 patients in whom the long-term outcome was known. The frequency of nuclear p53 staining was increased in non-diploid tumours (42%) when compared with diploid tumours (33%). Cytoplasmic p53 positive tumours were more common in the proximal colon (32%) than in the distal sites (21%). In univariate survival analysis, nuclear p53 and cytoplasmic staining were significantly associated with poor prognosis in patients with Dukes' A-C tumours. The patients showing both nuclear and cytoplasmic p53 staining had the poorest survival and the patients with tumours negative in both the nucleus and cytoplasm showed the best prognosis. The patients with tumours positive in the nucleus alone or in the cytoplasm alone presented an intermediate survival. In multivariate survival analyses, nuclear p53 expression, cytoplasmic p53 expression and DNA ploidy were prognostic indicators independent of Dukes' stage and each other. Further analysis suggested that the prognostic importance of cytoplasmic p53 expression was greater in diploid than in non-diploid tumours. We conclude that nuclear p53 expression, cytoplasmic p53 expression and DNA ploidy provide important prognostic information in colorectal adenocarcinomas.
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  • 3
    ISSN: 1573-7217
    Keywords: breast cancer ; CAM 5.2 antibody ; cytokeratin ; flow cytometry ; prognosis ; S-phase fraction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Estimation of S-phase fraction in breast carcinomas with single parameter flow cytometry may include errors due to dilution of cancer cells by host cells. Use of tissue specific markers may to some extent correct for the effect of dilution. S-phase fraction was estimated by flow cytometry with and without immunoselection in 80 DNA-euploid breast carcinomas in stage I-II. The tumor tissue was mechanically disintegrated and fixed in ethanol. A primary antibody, specific for cytokeratins 8 and 18, was added before incubation with the secondary FITC-conjugated antibody. S-phase fraction was calculated for both the gated (cytokeratin-positive) and the ungated cell population. An increasing proportion of tetraploid cells compared to diploid cells was found when the immunoselection method was used. The gated population tended to have a higher S-phase fraction than the ungated population. In univariate analysis S-phase fraction estimated from both ungated and gated cell populations yielded significant information for predicting recurrence when stratified for tumor size and nodal status. In bivariate analysis S-phase fraction of the gated population contributed prognostic information in addition to S-phase fraction of the ungated population when both variables were included in the analysis. Our conclusion is that S-phase fraction calculated from cytokeratin-positive cells provides prognostic information in addition to ungated S-phase values in DNA euploid breast carcinomas.
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  • 4
    ISSN: 1573-7217
    Keywords: breast cancer ; prognosis ; Nottingham histologic grade ; S-phase fraction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Flow cytometric DNA analysis with assessment of S-phase fraction and DNA ploidy was compared to Nottingham histologic grade. The study population consisted of 654 patients who presented between 1987 and 1996 with primary operable breast cancer and whose tumours had been analysed for S-phase fraction and DNA ploidy at the time of surgery. Grade, tumour size, node status, steroid receptor status, age, S-phase fraction and DNA ploidy were analysed univariately and multi-variately in a Cox proportional hazard analysis. In the univariate analyses all parameters were statistically significantly associated with breast cancer mortality during the follow-up period of 2–11 years. The most powerful predictor of death from breast cancer in the multiple regression analysis was grade. Patients with grade 1 tumours have excellent prognosis. We conclude that tumour grade is a strong prognostic indicator applicable to all breast cancer patients, regardless of size and nodal status, and advocate its general use.
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  • 5
    ISSN: 1573-7217
    Keywords: breast cancer ; DNA ; flow cytometry ; ploidy ; replication ; static cytofluorometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 332 primary invasive breast carcinomas were analysed by static cytofluorometry and flow cytometry. The ploidy distributions were similar, and 54% of the tumors were judged DNA aneuploid by both methods. The coefficient of variation of the G0–G1 peaks ranged from 2.0 to 8% with both techniques, but the mean was somewhat lower with flow cytometry — 4.1%, compared to 4.9% for the static measurements. The proportion of S-phase cells was possible to estimate from 80% of the flow histograms and 70% of the static histograms. S-phase was not estimated from the static histograms if less than 150 tumor cells were measured. With 160 tumors S-phase was measured by both methods. The range was 0 to 27% with the static measurements and 0.7 to 25% with flow cytometry. Corresponding mean values were 7.6% and 8.2%, which are similar to thymidine labeling index results with breast cancers reported in some studies. A close correlation was obtained (r = 0.927) comparing S-phase fractions estimated from aneuploid tumors with flow cytometry and static cytofluorometry if more than 200 cells were measured with the latter. The proportion of S-phase cells was significantly lower for the diploid tumors. We conclude that both techniques can be useful for the estimation of DNA ploidy and replication in human breast cancer.
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  • 6
    ISSN: 1573-7217
    Keywords: breast cancer ; recurrence ; prognosis ; post-recurrence survival ; metastasis ; S-phase ; mammography screening ; static cytofluorometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Using static cytofluorometry, S-phase was determined on the primary tumors of 421 patients with breast carcinomas in stages I–III diagnosed 1981–85 during the second and third screening rounds of a randomized trial evaluating the effect of mammographic screening. Through December 1988, 82 patients had developed local and/or distant recurrence, 51 of whom had died of cancer during the same period. The distribution among sites of recurrence differed between patients with tumors detected by mammography screening and cancers diagnosed due to clinical symptoms. The mean S-phase fraction was highest in patients with liver or brain metastases and lowest in patients with metastases in subcutaneous and cutaneous tissue and lymph nodes only. In univariate analysis, survival after first recurrence was significantly associated with the site of primary recurrence, the disease-free interval, and node status and tumor size at diagnosis, as well as the S-phase level. The median survival period was 31.3. months for patients with a S-phase fraction below 6%, and 10.7 months in cases with S-phase exceeding 10%. Neither ploidy nor the estrogen receptor content had significant influence on post-recurrence survival. In Cox's multiple regression analysis, only metastatic site, disease-free interval, and S-phase fraction showed significantly independent prognostic value.
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  • 7
    ISSN: 1573-7217
    Keywords: estrogen and progesterone receptor ; S-phase fraction ; tamoxifen ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A Swedish cooperative trial demonstrated that 5 years of adjuvant tamoxifen was more beneficial than 2 years of tamoxifen in the treatment of postmenopausal women with estrogen receptor (ER) positive, early stage, invasive breast cancer. The main aim of the present study was to investigate the importance of progesterone receptor (PgR) and ER concentration levels for patients participating in the trial and still distant recurrence free two years after the primary operation. Subgroup analyses revealed that only patients with ER positive and PgR positive breast cancer had improved distant recurrence free survival (DRFS) by prolonged tamoxifen therapy (p=0.0016). Patients with ER negative and PgR negative as well as ER positive and PgR negative tumors showed no significant effect of prolonged tamoxifen (p=0.53 and p=0.80, respectively). The percentage of ER negative and PgR positive breast cancers was too small (2.2%) for any meaningful subgroup analysis. There was a significant positive trend that the concentration level of PgR (high positive vs. low positive vs. negative) decreased the recurrence rate for those with prolonged therapy. No corresponding pattern was found for the ER content. S-phase fraction did not correlate to the recurrence rate of PgR positive breast cancers. Patients recurring during tamoxifen therapy had receptor negative tumors to a greater extent than those recurring after tamoxifen treatment. In conclusion, prolonged tamoxifen therapy for 5 years instead of 2 years was found to be beneficial for patients with ER positive and PgR positive breast cancer, whereas three extra years of tamoxifen had little or no effect for patients with ER positive but PgR negative tumors as well as for steroid receptor negative patients.
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