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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 216 breast cancer patients, the prognostic value of current biological factors (c-erbB-2, EGF-receptor, p53, PCNA-proliferative fraction) was compared with that of conventionally histomorphologic features (histologic type, histologic grade, tumour size, hormonal receptor status). After a 66(6 - 109) months' median follow-up survival was significantly correlated with histological grade (p = 0.014) and PCNA-proliferative activity (p = 0.015). The prognostic influence of oestrogen receptor (ER)- and progesteron receptor (PR-)status achieved borderline significance (ER/p = 0.07; PR/p = 0.05). Neither c-erbB-2, EGF-R, p53 nor any of the other factors showed any correlation to survival. In the multivariate analysis, histological grade was revealed as the only independent prognostic factor. The prognostic value of PCNA was second to histological grade and if grade was excluded from the analysis, PCNA-expression became the only independent factor. Thus, in individual cases the PCNA-proliferative fraction could help the clinician to decide on the therapy.
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PMID:[C-erbB-2, EGF receptor, p53 and PCNA. The prognostic significance of recent tumor markers for lymph node negative breast cancer]. 854 29

Immunocytochemical studies examining the Ki-67 proliferation marker in paraffin-embedded material have recently been made possible by the availability of several antibodies, notably MIB-1, which are readily applicable to microwaved sections. Using breast cancer material, the present study examines correlations shown by these new paraffin assays and also by PCNA (proliferating cell nuclear antigen), an existing marker of proliferation, with the established Ki-67 cryosection assay. Paraffin sections were microwaved prior to incubation with Ki-67 or MIB-1 antibodies. Signal detection was carried out with a biotinylated secondary antibody, peroxidase-conjugated streptavidin, and DAB/H2O2 chromogen. The results suggest that caution is required when studying proliferation in paraffin-embedded breast cancers by immunostaining using Ki-67 antibodies. Nuclear staining in wax sections (Ki-Par, MIB-1, PCNA) greatly exceeded that in cryosections (Ki-Froz) and thus correlations were notably absent between Ki-Par or PCNA immunostaining and the routine Ki-Froz assay. Immunostaining with MIB-1 or PCNA may, however, be useful to assess proliferation if cut-offs are applied to eliminate weak immunostaining associated with wax sections. Thus, an approximately linear relationship was seen between MIB-1/Ki-Froz, which was improved if only moderately or moderately/strongly MIB-1-positive cells were scored. Similarly, a significant correlation was also revealed between PCNA/Ki-Froz if such a cut-off was applied.
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PMID:A cautionary note regarding the application of Ki-67 antibodies to paraffin-embedded breast cancers. 855 91

There is ample evidence that the protease urokinase plasminogen activator (uPA) plays a role in invasion and spread of tumours. Several publications suggest its biochemical measurement in tumour cytosols to be of prognostic significance in breast carcinomas. Our study set out to determine whether the immunohistochemical detection of uPA in formalin-fixed, paraffin-embedded primary breast cancer tissues is of prognostic relevance. We tested 269 surgical specimens of primary ductal infiltrating carcinoma immunohistochemically using a modified avidin-biotin method. Some 57% of carcinoma specimens yielded specific positive staining in tumour cells. Detection of uPA correlated to tumour grade (P = 0.04), and to the detected level of the proliferation marker PCNA (P = 0.002), but not to patients' age or menopausal status, tumour size, nodal or steroid receptor status (P > 0.05). At median 68 months' follow-up, 34% of patients had experienced tumour relapse and 28% had died from cancer. Clinical course was correlated significantly to tumour size, tumour grade, nodal and steroid hormone receptor status (P < 0.05). Immunohistochemical detection of uPA, however, could not be demonstrated to be of any prognostic significance with regard to relapse-free or overall survival (P > 0.05) in the total study group or in the N0 (n = 120) and N + (n = 144) subgroups, regardless of whether univariate or multivariate analysis was applied.
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PMID:[Prognostic value of immunohistochemical determination of urokinase plasminogen activator in primary breast cancers]. 857 May 58

The influence of oral contraceptives (OC) on histomorphological and molecular biological prognostic factors was studied in 471 breast cancer patients. Differences in histological tumor type, histological grade, tumor size, lymph node status, hormonal receptor status, PCNA expression and c-erbB-2 protein overexpression were investigated in relation to the duration of OC use (< 5 years/ > or = 5 years) and the time since last use. A total of 297 (63%) patients had used oral contraceptives at some time in their life; 186 patients (39.5%) had used OC's for 5 years or more. There were no significant differences in the tumor characteristics investigated with respect to OC use in general. Neither long-term use at some time in their life nor long-term use until breast cancer diagnosis had an effect on histomorphological and molecular biological factors. Thus, steroid hormones contained in OC's had no direct effect on prognostic factors in breast cancer.
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PMID:[C-erbB-2, PCNA and histomorphologic factors in breast carcinoma after oral contraceptive use]. 871 Jul 91

The immunoreactivity for Ki-67 and PCNA was investigated in 487 patients with primary breast carcinomas using MIB-1 (Immunotech, France) and PC-10 (DAKO, Denmark) as primary antibodies. Formalin-fixed and paraffin-embedded tissue sections were used. The immunoreactivity for Ki-67 and PCNA was found to be independent of the length of fixation if the sections were pretreated in a microwave oven in citrate buffer and distilled water, respectively. The immunostaining was evaluated semiquantitatively. High Ki-67 score (more than 1% positive tumour cells) and PCNA over-expression (more than 25% positive tumour cells) were correlated with clinicopathological parameters such as large tumour size, high histological grade (poor differentiation), and absence of steroid hormone receptors, which are parameters of an aggressive phenotype of the tumour. In univariate analysis of survival data, both Ki-67 and PCNA were parameters of a poor overall survival in both lymph node-positive and -negative patients. In multivariate anlaysis using a Cox model stratified by nodal status, Ki-67 and PCNA failed to be of prognostic significance whereas classical histopathological parameters such as tumour size and histological grade turned out to be of independent prognostic significance in both lymph node-positive and -negative patients, while progesterone receptors were of independent prognostic significance only in lymph node-positive patients.
Breast Cancer Res Treat 1996
PMID:Correlation of growth fraction by Ki-67 and proliferating cell nuclear antigen (PCNA) immunohistochemistry with histopathological parameters and prognosis in primary breast carcinomas. 875 May 78

The expression of aromatase by breast cancer cells and the role of locally produced estrogen in the stimulation of tumor growth has been controversial. The present study was performed to determine the site of aromatization in human breast cancers, using both immunocytochemistry and in situ hybridization. The functional significance of locally produced estrogens on growth of the tumor was addressed by measuring aromatase activity and a marker of proliferation (PCNA score). In addition, histocultures of some tumors were carried out to investigate whether testosterone aromatization could stimulate tumor proliferation. Of the 19 tumors investigated, 10 (52.6%) showed significant immunoreactivity to antiaromatase antibody in the cytoplasm of tumor epithelial cells and in surrounding stromal cells. The presence of aromatase mRNA detected by ISH was also located in tumor epithelial cells and stromal cell, and the pattern of expression was the same as with immunocytochemistry. In the ten tumors that showed immunoreaction to aromatase, the average aromatase activity measured in cryosections was 286.5 +/- 18.6 (SE) fmol estrogen/mg protein.h, whereas in nine tumors with weak aromatase immunoreaction, the enzyme activity was 154.7 +/- 19.3 (SE) fmol estrogen/mg protein-h (P < 0.05). The mean PCNA score was 33.8 +/- 5.1 (SE)% in strongly stained tumors and 20.8 +/- 2.0 (SE)% in weakly stained tumors (P < 0.05). Aromatase activity level and PCNA score were significantly correlated. In histoculture of four tumors, estradiol increased the incorporation of [3H]-thymidine into DNA. In two of these tumors, aromatase activity was high and [3H]-thymidine incorporation into DNA was also stimulated by testosterone. In the other two tumors that had low aromatase activity, no such stimulation occurred with testosterone. The results indicate that aromatase is expressed mainly in tumor epithelial cells and that sufficient amounts of estrogen are synthesized by the tumor to produce a proliferative response. It is concluded that estrogen synthesis by cancer cells could play a important role in promoting growth in a significant proportion of breast tumors.
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PMID:Expression of aromatase protein and messenger ribonucleic acid in tumor epithelial cells and evidence of functional significance of locally produced estrogen in human breast cancers. 877 Sep 32

The breast is a target organ for estrogens and progesterone. These hormones control several functions of the normal and abnormal mammary epithelium including cell proliferation. Most of the actions of estrogens and progesterone are mediated via specific steroid receptors, and one would expect that proliferating cells should contain estrogen receptors (ER) and/or progesterone receptors (PR). However, the correlation between receptor expression and cell proliferation is still controversial. In the present study we have examined 29 human breast cancer samples; in 17 of them we evaluated the simultaneous ER and PR localization with that of proliferating cell nuclear antigen (PCNA) and silver-stained nucleolar organizer regions (AgNORs) in a cell-by-cell study. We found that in almost 50% of the tumor biopsies examined, the cells expressing ER were significantly associated with elevated cell proliferation. In another group (38%) there were not significant differences between ER expression and cell proliferation. In only one of the samples (6%) the cells expressing ER showed lower cell proliferation. The study also revealed that in 44% of the tumors the PR expressing cells were associated with elevated cell proliferation. In a second group the PR expression was not significantly associated with cell proliferation (33% of the cases). Finally, in 22% of the samples the cells carrying PR showed lower cell proliferation. We also detected lower ER immunoreactivity in 30% of the breast cancer biopsies with one of the monoclonal antibodies against ER (antibody 1D5 directed against the A/B domain). This group of tumors was PR-negative (or very weakly positive) and had high proliferation. The presence of tumors with 'abnormal' ER proteins and displaying ER/PR significantly associated with elevated cell proliferation could have implications in human breast cancer treatment.
Breast Cancer Res Treat 1996
PMID:Estrogen receptors, progesterone receptors, and cell proliferation in human breast cancer. 882 33

We examined the effects of recombinant human interleukin 11 (rhIL-11) on in vivo human hematopoiesis. Twelve women with advanced breast cancer and no evidence of bone marrow (BM) involvement were treated with 10, 25, 50, or 75 micrograms/kg/day of rhIL-11 administered subcutaneously for 14 consecutive days. Examination of bone marrow trephine biopsies obtained before and after rhIL-11 treatment revealed unchanged BM cellularity at all doses, and a statistically significant increase in megakaryocyte (MK) frequencies (from 0.5 +/- 0.1% to 1.0 +/- 0.3%) following administration of the two highest doses (p < 0.001). The BM biopsies also showed an increased proportion of immature myeloid and erythroid precursors following 14 days of treatment in all cases. The mean proportion of marrow cells stained with PC10, a monoclonal antibody (mAb) that recognizes the proliferating cell nuclear antigen (PCNA), increased from 16.3 +/- 5.7% to 45.8 +/- 17.1% (p < 0.001) following the two highest treatment doses. Most of the PC10+ cells were promyelocytes and proerythroblasts. In this same group, the proportion of PC10+ MKs increased from 28.3 +/- 11.5% to 56.8 +/- 24.3% (p < 0.01) after treatment, while megakaryocyte ploidy analysis revealed a greater number of higher ploidy (64N) megakaryocytes following rhIL-11 treatment (p < 0.012). Numbers of BM and peripheral blood (PB) CD34+, CD34+DR+, and CD34+DR- cells did not change following rhIL-11 treatment. Following rhIL-11 therapy at the highest dose studied, a 3- and 10-fold increase in the number of committed BM MK progenitor cells (CFU-MK) was observed in two of three patients, while no change was seen in the number of the other BM or PB progenitor cells examined. rhIL-11 administration was also associated with an increase in BM reticulin content (fibrosis grade 1-2) in 7 patients. These results indicate that the administration of rhIL-11 to patients with normal hematopoiesis stimulates MK endoreduplication, PCNA expression, and, at high doses, increases MK and CFU-MK progenitor cell numbers. In addition, rhIL-11 was able to stimulate precursor cells of different marrow lineages without affecting the number of assayable progenitor cells.
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PMID:Effects of recombinant human interleukin-11 (Neumega rhIL-11 growth factor) on megakaryocytopoiesis in human bone marrow. 886 39

Heat shock proteins (hsps) are thought to play important roles in the cell cycle and various processes of carcinogenesis. Therefore, we evaluated the expression of hsps, mainly hsp90 and hsp70, in human breast cancer tissues. Hsp90alpha mRNA was expressed at much higher levels in the cancerous tissue than in the non-cancerous tissue. In addition, a close correlation between hsp90alpha mRNA expression and the proliferating-cell-nuclear-antigen labeling index (PCNA LI) was observed for the cancerous tissue. These findings suggest that increased expression of the hsp90alpha isoform may play a role in cell proliferation. On the other hand, hsp90beta mRNA expression was significantly higher in poorly differentiated carcinomas than in well differentiated carcinomas of the breast. The intracellular localization of hsp70 was consistent with that of ubiquitin. In specimens showing hsp70 in the nucleus, the PCNA LI was significantly high. Hsc73 mRNA, a member of the hsp70 family, was also expressed at higher levels in cancerous tissues associated with a high PCNA LI than in non-cancerous tissues. These results suggest that hsp90alpha may play a role in cancer cell proliferation and that hsp90beta may contribute to cell differentiation and structural constitution. In addition, hsp70, especially hsc73, is related to ubiquitin and seems to be a marker for cancer proliferation.
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PMID:Expression and roles of heat shock proteins in human breast cancer. 887 52

The evaluation of the immunohistochemical expression of epidermal growth factor receptor (EGFR), c-erbB-2 oncoprotein, proliferating indices Ki-67, and PCNA were determined on 68 primary breast carcinomas. These markers were correlated with each other and with other clinicopathological variables such as: age, tumor size? histotype, tumor grade and steroid receptors' content as well as nodal status. The monoclonal antibodies anti-human Epidermal Growth Factor Receptor (EGFR1), anti-human Ki67 (DAKO) and N13259 (Oncogene Science) were applied to paraffin and frozen tissue sections. All markers showed an heterogeneous pattern of staining. There was almost equally high staining intensity at the membranus for EGFR and c-erbB-2 in about 32% of the cases. The EGFR and c-erbB-2 positive cases were much less common in infiltrating lobular (2,2/13) rather than in ductal adenocarcinomas (21,20/55). The low grade carcinomas showed low expression of EGFR and c-erbB-2 oncoprotehl comparing with high grade ductal adenocarcinomas. A high index of Ki-67 was correlated with EGFR and c-erbB-2 membrane positivity. There was an inverse relationship between the expression of c-erbB-2 and EGFR, when compared with oestrogen receptors' content. A significant correlation was also demonstrated between EGFR and c-erbB-2 immunoreactivity with lymph node status. Our results provide evidence that the synchronous immunohistochemical detection of EGFR, c-erbB-2 and Ki-67 may be of useful significance in breast cancer patients, especially when combined with other clinicopathological variables. Furthermore the expression of EGFR and c-erbB-2 oncoprotein may affect the cell proliferation and differentiation.
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PMID:The prognostic significance of epidermal growth factor receptor (EGFR), C-erbB-2, Ki-67 and PCNA expression in breast cancer. 892 Jul 82


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