Biomedical subjects

C Allasia

Publications and source records attributed to C Allasia.

At least 19 recordsLinked to original sources

PubMed2004

Prediction of metastasis risk (11 year follow-up) using VEGF-R1, VEGF-R2, Tie-2/Tek and CD105 expression in breast cancer (n=905).

Neoangiogenesis in tumours contributes to the development of blood-borne metastases, and can be evaluated by markers of activated endothelial cells in preference to panendothelial markers. Our purpose was to document the prognostic significance of VEGF-R1, VEGF-R2, Tie-2/Tek and CD105 immunoexpression in breast carcinoma frozen samples (n=905, follow-up=11.7 years). We observed that: (i). CD105 (P=0.001) and Tie-2/Tek (P=0.025) (but not VEGF-R1 and VEGF-R2) overexpression correlated with a shorter survival, and were (Cox's model) independent histoprognostic indicators; (ii). only CD105 marked expression correlated (P=0.035) with a shorter survival of node-negative patients; (iii). three markers - CD105 (P=0.001), Tie-2/Tek (P=0.01), VEGF-R1 (P=0.001), but not VEGF-R2 - correlated with metastatic risk in node-negative patients in univariate analysis; and (iv). VEGF-R1 (P=0.01) expression correlated with high local recurrence risk. It is concluded that CD105 and to a lesser extent Tie-2/Tek and VEGF-R1, but not VEGF-R2 are endowed with prognostic significance that may be useful for patient monitoring, particularly CD105 expression for selecting node-negative patients for more aggressive postsurgery therapy.

Adult↗

PubMed2002

Down-modulation of nuclear localisation and pro-fibrogenic effect of 4-hydroxy-2,3-nonenal by thiol- and carbonyl-reagents.

Among the oxidative breakdown products of omega-6 unsaturated fatty acids, the aldehyde 4-hydroxy-2,3-nonenal (HNE) is receiving increasing attention for its potential pathophysiological implication, which at least partly lies on the demonstrated ability to modulate gene expression of a number of genes. Here we show that a marked down-modulation of HNE nuclear localisation in cells of a macrophage line (J774-A1) can be afforded by treatment with sulfydryl and carbonyl reagents without significantly interfering with cell viability. As regards the addition of thiol-group reagents to the cell suspension, N-ethylmaleimide (NEM) led to a sustained decrease of HNE nuclear localisation, while 4-(chloromercuri)-benzene-sulfonic acid (PCMBS) gave a similar but more transient effect. Hydroxylamine (HYD), a carbonyl-group reagent, was also able to inhibit HNE nuclear localisation. The actual efficacy of the inhibitors used was then tested on the HNE-induced stimulation of transforming growth factor beta1 (TGFbeta1) production by J774-A1 cells. Indeed, the thiol reagents NEM and PCMBS, both markedly down-modulating HNE nuclear localisation, were able to inhibit HNE-induced increase of TGFbeta1 protein synthesis. The carbonyl reagent HYD was less effective on this respect, producing strong but incomplete protection against HNE-induced TGFbeta1 increase. Taken together, the results indicate that sulfydryl groups are involved in the process of HNE cellular internalisation, while both sulfydryl and carbonyl groups are involved in the process of HNE nuclear translocation, and consequently in the modulation of gene expression by the aldehyde. Further, an actual demonstration is provided that HNE-induced effect on gene regulation can be efficiently counteracted by suitable interference with HNE biochemistry.

Aldehydes↗

PubMed2000

Regulation of thyroid cell volumes and fluid transport: opposite effects of TSH and iodide on cultured cells.

Cell volume regulation by thyrotropin (TSH) and iodide, the main effectors involved in thyroid function, was studied in cultured thyroid cells. The mean cell volume, determined by performing 3-D reconstitution on confocal microscopy optical slices from living octadecylrhodamine-labeled cells cultured with both TSH and iodide (control cells), was 3.73 +/- 0.06 pl. The absence of iodide resulted in cell hypertrophy (136% of control value) and the absence of TSH in cell shrinkage (81%). These changes mainly affected the cell heights. The effect of TSH on cell volume was mediated by cAMP. The proportion of cytosolic volume (3-O-methyl-D-glucose space vs. total volume) decreased in the absence of iodide (85% of control value) and increased in the absence of TSH (139%), whereas protein content showed the opposite changes (121 and 58%, respectively). The net apical-to-basal fluid transport was also inversely controlled by the two effectors. Iodide thus antagonizes TSH effects on cell volumes and fluid transport, probably via adenylylcyclase downregulation mechanisms. The absence of either iodide or TSH may mimic the imbalance occurring in pathological thyroids.

3-O-Methylglucose↗

PubMed2000

Endometrial response to sexual steroids as assessed by prostaglandin F(2alpha) output in explant culture and hormone receptor expression.

The objective of this study was to evaluate the endometrial response to sexual steroids in organ culture using two means: prostaglandin (PG) F(2alpha) output in medium culture and steroid receptor immunoexpression in tissue. Human endometrium samples were classified in homogeneous and heterogeneous proliferative or secretory subsets. In proliferative endometrium explant culture, progesterone (10(-7) M) induced a significant decrease in PGF(2alpha) output, but this was not the case in secretory endometrium, whereas no significant effect of estradiol (10(-8) M) was observed. Before culture, homogeneous and heterogeneous proliferative endometrium presented the same pattern of estradiol receptor (ER) and progesterone receptor (PR) expression evaluated by quantitative immunocytochemistry. After culture, immunoreactive ER and PR were detected on the explant. PR immunoexpression rates after culture were lower than before culture in glands on homogeneous proliferative and in stroma on heterogeneous proliferative endometrium explants without in vitro steroid addition. In secretory endometrium, no significant difference was observed between ER or PR immunoexpression rates before culture and after culture. These results provided the hormonal receptivity status of endometrium after culture and will thus serve as a reference for evaluating in vitro steroid effects on endometrium explants. Our preliminary results suggest that cultures of endometrium explants are a valid model for studying the effects of hormonal treatment on homogeneous as well as heterogeneous endometrium. These data could be particularly relevant for evaluating the potential response to hormone stimulation and treatment of endometria sampled in perimenopausal patients.

Culture Techniques↗

PubMed2000

Quantitative analysis of glycogen content in hepatocytes of human liver allograft after ischemia and reperfusion.

In order to examine glucose metabolism in liver grafts after cold ischemia and reperfusion, the heterogeneous lobular distribution pattern of glycogen content was studied using histochemical quantitative analysis. In most of the cases, this heterogeneous pattern of glycogen was observed after preservation and reperfusion. However, a 42% reduction of glycogen content, expressed as the ratio between stained surface and total surface of liver biopsies, was observed in biopsies after reperfusion. Moreover, both periportal and centrilobular hepatocytes showed a significant decrease in mean optical density after reperfusion (18% and 25%, respectively). The comparison of our results to early postoperative liver function tests and cold ischemia times showed no significant correlation (p<0.05).

Adolescent↗

PubMed1999

E-cadherin and beta-catenin expression in breast medullary carcinomas.

The initial step of cancer invasion and metastasis is the escape of tumour cells from the primary site, involving disruption of normal cell-cell adhesion and E-cadherin (E-cad) and beta-catenin (beta-cat) down-regulation, as shown in various types of human malignancies including breast carcinomas. Medullary carcinomas are high grade and poorly differentiated tumours with syncytial typical pattern, and prognosis unexpectedly better than that in high grade breast carcinomas. In a series of 55 breast typical medullary carcinomas diagnosed according to the strict use of Ridolfi et al (Cancer 40: 1365-1385, 1977) criteria, E-cad and beta-cat were investigated using quantitative (SAMBA 2005 system) immunocytochemical assays on frozen sections. Results were compared to that obtained on paraffin sections and in a series (n=55) of grade 3 ductal carcinomas. It was shown that medullary carcinomas significantly (p<0.001) expressed more E-cad and beta-cat than grade 3 ductal carcinomas. E-cad and beta-cat correlated with high expression of P53, of c-erbB, and of Ki-67 antigens, and with lack of hormone receptors antigenic sites (p<0.001). It was concluded that favourable prognosis and syncytial pattern of typical breast medullary carcinomas likely results, at least partly, from a particular expression of cell-cell adhesion molecules, significantly limiting tumour growth and efficiently mastering the tumour cell dissemination, opposing to high proliferative activity (grade 3).

Adult↗

PubMed1998

Prognostic significance of Nm23/NDPK expression in breast carcinoma, assessed on 10-year follow-up by automated and quantitative immunocytochemical assays.

The Nm23 gene has been described as an antimetastatic gene; in some studies, disease progression in patients with solid tumours is related to Nm23 protein expression, which can be detected by immunohistochemical procedures. Detection of Nm23-H1 protein in breast cancer may be relevant for the monitoring of patient therapy, provided that the technical procedures are reliable and cost-effective. The aim of the present study was to determine the prognostic significance of Nm23, assessed by quantitative immunocytochemical assays (Nm23 ICAs), under optimal technical conditions. Nm23-H1 ICAs were performed on frozen sections, using an automated immunoperoxidase technique (Ventana) and computer-assisted analysis of digitized colour microscopic images (SAMBA), in a series of 168 breast carcinomas. The results of automated quantitative ICAs were correlated with patients' follow-up (129 months). Nm23-H1 immunocytochemical expression in histological sections of tumours in which more than 3 per cent of the surface area was positively stained was significantly (0.012) correlated with longer metastasis-free survival in both node-positive and node-negative groups of patients (P = 0.032 and P = 0.036, respectively) (Kaplan-Meier log-rank test, NCSS 6.0.1 software). Nm23 expression (cut-point 3 per cent) did not, however, correlate with overall survival, or with the recurrence-free survival. In multivariate analysis (proportional hazards regression, Cox model), the prognostic significance of Nm23 in terms of metastasis-free survival was independent of tumour size and grade, and of histological grade, in the entire cohort of patients. It is concluded that Nm23 immunodetection is only of limited practical clinical relevance in breast carcinoma, even when assessed under optimal technical conditions.

Adult↗

PubMed1998

Reduced E-cadherin immunohistochemical expression in node-negative breast carcinomas correlates with 10-year survival.

E-cadherin immunodetection was performed on frozen sections, using an immunoperoxidase procedure and with computer-assisted analysis of digitized colored microscopic images in a series of 179 breast carcinomas. Quantitative immunocytochemical assays were correlated with follow-up (129 months). The results showed that reduced E-cadherin immunocytochemical expression in tumors (cut point, 4%) significantly correlated with shorter overall survival in node-negative patients (Kaplan Meier log rank test). But E-cadherin immunostained expression (cut point, 4%) did not correlate with metastasis-free or recurrence-free survival. In multivariate analysis (Cox proportional hazards regression model), E-cadherin prognostic significance for overall survival in node-negative patients was independent of the tumor size, grade, and histologic type. The results suggest that reduced E-cadherin expression detected in optimum technical conditions (frozen samples and quantitative immunohistochemistry) is an independent indicator of poor survival in node-negative patients and may be clinically relevant for the treatment of patients with breast carcinomas.

Adult↗

PubMed1998

bcl-2 automated and quantitative immunocytochemical assays in breast carcinomas: correlation with 10-year follow-up.

PURPOSE: bcl-2 protein is detectable in human cancers and may be involved in the response to antineoplastic drugs or endocrine therapy in breast carcinomas. In a previous study, we had developed optimal technical conditions for bcl-2 immunodetection. The aim of the present report was to determine the prognostic significance of bcl-2 expression in breast carinomas by the use of a similar immunocytochemical procedure. METHODS: bcl-2 immunocytochemical assays were performed on frozen sections by automated immunoperoxidase technique (Ventana) and computer-assisted analysis of digitized colored microscopic images (SAMBA) in a series of 170 breast carcinomas. The results of automated quantitative immunocytochemical assays were correlated with patient follow-up (120 months). RESULTS: Intense bcl-2 immunocytochemical expression in tumors (cutpoint, 15%) significantly correlated with longer disease-free survival and longer recurrence-free survival in the entire cohort of patients (P = .028 and P = .035, respectively) and also in node-negative subgroups of patients (P = .028 and P = .01; Kaplan-Meier long-rank test; NCSS 6.0.1 software). But bcl-2 immunostained surfaces (cutpoint, 15%) did not correlate with overall survival. In multivariate analysis (proportional hazards regression, Cox model), bcl-2 prognostic significance in terms of disease-free survival was only independent of the tumor size and grade and histoprognostic index (Nottingham prognostic index [NPI]). CONCLUSION: bcl-2 immunohistochemical expression is a significant indicator of favorable outcome only in terms of disease-free and local recurrence-free survival. However, bcl-2 expression in tumors is an independent weakly prognostic indicator in breast carcinomas. bcl-2 immunodetection assessed in optimal technical conditions (frozen samples, automation, quantitative analysis, scatter diagram cutoffs) may have some limited practical clinical relevance for the management of patients with breast carcinomas.

Adult↗

PubMed1997

Automated and quantitative immunocytochemical assays of Nm23/NDPK protein in breast carcinomas.

A series for Nm23-protein immunodetection was investigated in human breast carcinomas. Frozen sections were processed by automated immunoperoxidase procedure, and immunoprecipitates in positive tumors were quantified by processing digitized microscopic images. Nm23 immunohistochemical expression in tumors was correlated with clinicopathological data and with intra-tumoral proteins also detected by automated and quantitative immunohistochemistry. A positive Nm23 immunoreaction was observed in 58% of tumors, within cell cytoplasm. Nm23 expression was independent of the patient's age, and of tumor size, type and grade, but an inverse relationship was observed between Nm23 expression and axillary-lymph-node metastasis. An inverse relationship was also observed between Nm23 and P-53, CD-31, cathepsin D, tenascin and P-gp immunohistochemical expressions. But Nm23 expression was independent of c-erb-B product, growth fraction (MIB1/Ki67), and immunohistochemical expression of hormone receptors/P-S2. The results suggest that the anti-metastatic nm23 gene may partly act upon the regulation of tumor-cell proliferation (correlation with P-53) and may have some effects on epithelial-cell/stroma interactions (regulation of extracellular-matrix protease and of angiogenesis) independently of hormone sensitivity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1997

Leukosialin (CD43) behavior during adhesion of human monocytic THP-1 cells to red blood cells.

To understand the modulation and the behavior of glycocalyx elements during adhesion, we explored one of its components, the CD43 molecule, on human monocytic THP-1 cells exposed to cytokine stimulation and its redistribution during heterotypic adhesion to opsonized erythrocytes. First we demonstrated by immunofluorescence and immunoprecipitation that CD43 is dys-sialylated in monocytic THP-1 cells stimulated by interferon-gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) and stimulation increased correlated to heterotypic adhesion. CD43 anti-adhesive effect seemed to be related to sialic acid moeties because an increase in adhesion was also induced by sialidase treatment and by monoclonal antibodies recognizing sialic acid-dependent epitopes on CD43. Second, a redistribution of CD43 molecules was observed after adhesion, resulting in the exclusion of CD43 molecules from contact areas as demonstrated by immunofluorescence and by ultrastructural immunogold localization. We therefore demonstrated in monocytic THP-1 cells that some glycocalyx molecules can be modulated by cytokines and redistributed during adhesion. These results support the concept that CD43 can regulate cell interactions.

Antibodies, Monoclonal↗

PubMed1997

Automated and quantitative immunocytochemical assays of CD44v6 in breast carcinomas.

CD44 variants carrying sequences encoded by exon v6 are preferentially expressed in metastatic animal cancer cell lines. CD44v6 overexpression correlates tumor dedifferentiation and progression in some human carcinomas, but the relationship of CD44v6 overexpression with metastatic behavior of tumor observed in animal models is controversial, particularly in breast carcinomas. The discrepancies probably result from analytical bias. We investigated CD44v6 and CD44s expression in 218 frozen samples of primary breast carcinomas. Immunocytochemical procedure was performed under optimal technical conditions using commercially available 2F-10 monoclonal antibody (MAb), a microprocessor-controlled automated device (Ventana Medical Systems, Tucson, AZ), and quantitative evaluation of results by processing digitized-colored microscopic images (SAMBA, Grenoble, France). CD44v6 expression in tissue sections was shown to be independent of the patient age, tumor size, histological types and grades, and the lymph node status. CD44v6 expression was also independent of the expression of molecules endowed with poor prognostic significance detected by MAbs (anti-p53, anti-c-erb B-2 protein, MIB1) on consecutive sections. No significant relationship could be evidenced either between CD44v6 expression, and CD31 involved stromal angiogenesis and cathepsin D. Finally, CD44v6 was independent of markers of hormone dependence (estrogen and progesterone receptors, pS2) and of multidrug resistance (P-glycoprotein). Similar results were observed with anti-CD44s. We conclude that the true prognostic significance of CD44v6 overexpression still remains to be shown under rigorous technical conditions (frozen samples, well-documented MAbs, and optimal standardization of procedure using automation and quantitative analysis) providing data appropriate for further correlation with long-term patient follow-up.

Adult↗

PubMed1997

c-erbB-2 oncoprotein detected by automated quantitative immunocytochemistry in breast carcinomas correlates with patients' overall and disease-free survival.

The prognostic significance of c-erbB-2 oncoprotein overexpression detected in tumours by immunocytochemical assays (ICAs) was investigated in 148 breast carcinomas. ICAs were performed under optimal technical conditions with frozen tissue sections and included automated immunoperoxidase technique and computer-assisted analysis (densitometry) of digitized coloured microscopic images. Results of quantitative ICAs (expressed in percentages of c-erbB-2-positive surfaces and mean optical densities) were correlated with the patients' follow-up in axillary lymph node-positive (N+) and node-negative (N-) subgroups of patients. Patients' follow-up ranged from 9 months (for the first death) to 101 months (for the 121 alive patients) with a 62.5 months mean overall follow-up. It was shown that marked c-erbB-2 immunocytochemical expression in tumours (cut-off point 35%) significantly correlated with the patients' poor overall survival in N+ and in N- patients (Kaplan-Meier, log-rank test, P = 0.045 and P = 0.015). Also, marked c-erbB-2 immunohistochemical expression correlates with short disease-free (P = 0.005), recurrence-free (P = 0.048) and metastasis-free survival (P = 0.05) (Kaplan-Meier, log-rank test) in N+, but not in N- subgroups. It is concluded that in optimal conditions (automated and quantitative ICAs on frozen sections) c-erbB immunohistochemical expression is a significant prognostic indicator in terms of overall and disease-free survival. The c-erbB-2 protein prognostic significance is independent of node status in terms of overall survival, but not of disease-free survival.

Adult↗

PubMed1997

Automated and quantitative immunocytochemical assays of Bcl-2 protein in breast carcinomas.

Expression of the bcl-2 gene was investigated in 218 human breast carcinomas by immunohistochemical analysis. Immunodetections were assessed using (1) frozen sections, (2) documented commercially available monoclonal antibody (bcl-2/124, Dako), (3) automation of immunoperoxidase technique (Ventana) and (4) quantitative evaluation of results by image analysis (SAMBA) and statistical analysis of quantitative data (BMDP software). Bcl-2 protein expression was correlated with current prognostic indicators and with molecular markers detected by the same procedure as for Bcl-2. It was shown that Bcl-2 expression is not related to patients' age, tumour size and type or lymph node status, but an inverse relationship was observed between Bcl-2 and tumour grade (P < 0.0001). An inverse relationship was also observed between Bcl-2 expression and p53 (P < 0.0001), Ki67/MIB1 antigen- (P = 0.0012), and P-gp- (P = 0.002) positive immunoreactions. In contrast, anti-Bcl-2 positive reaction was significantly associated with ER-positive (P < 0.001) and with ER/PR-positive or ER/PR/pS2-positive immunoreactions (P < or = 0.005). Bcl-2 expression was independent of CD31 and cathepsin D expression. Thus, Bcl-2 protein, thought to be antiapoptotic, exhibits parodoxical expression in human breast carcinomas. It is strongly detected in low-grade tumours (well-differentiated) with low (MIB1) growth fraction, but is independent of the tumour progression (size, node status, CD31, and cathepsin D). Bcl-2 acting on apoptosis is related to p53 gene abnormalities in breast carcinomas. Bcl-2 protein expression may also be involved in response to endocrine therapy (associated to ER/PR/pS2 positive immunoreactions) and probably with chemoresistance mechanisms (inverse relationship with P-gp).

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1997

CD31/PECAM automated and quantitative immunocytochemical assays in breast carcinomas: correlation with patient follow-up.

The purpose of this study was to determine the prognostic significance of quantitative CD31 immunohistochemical assays. CD31 assays were performed on a series of 167 breast carcinoma specimens under optimal technical conditions that involved frozen sections, an automated immunoperoxidase technique, and computer-assisted analysis of digitized colored microscopic images. Results of automated quantitative immunohistochemical assays were correlated with patient follow-up (9.6 years). Patients were divided into two subgroups: those who had axillary lymph node-positive (N+) disease and those who had lymph node-negative (N-) disease. The marked immunocytochemical expression of CD31 in tumors (cutoff point, 20%) was significantly (P = .033) associated with a poor overall survival rate (Kaplan-Meier, log rank test); however, a significant association was not observed in the N+ and N- subgroups. CD31-immunostained tumor cell surfaces larger than 20% correlated with the metastasis-free survival rate (P = .004) in all patients and in the N+ subgroup (P = .005) but not in the N- subgroup. In addition, marked immunocytochemical expression of CD31 correlated with the short-term disease-free survival rate (P = .04) in the N+ subgroup but not in the N- subgroup. In multivariate analysis (proportional hazards regression, Cox model) the prognostic significance of CD31 was independent of tumor size and histologic type but not of grade. The results suggest that, under optimal technical conditions (automated and quantitative immunohistochemical assays on frozen sections), immunohistochemical expression of CD31 is a significant prognostic indicator of overall and metastasis-free survival rates. CD31 has limited prognostic value, however, and is not a completely independent prognostic indicator because it is related to nodal status.

Adult↗

PubMed1997

Cathepsin D detected by automated and quantitative immunohistochemistry in breast carcinomas: correlation with overall and disease free survival.

AIM: To determine the prognostic significance and clinical relevance of cathepsin D detected by immunocytochemical assays (ICAs) in breast carcinomas. METHODS: 151 patients presenting with palpable or impalpable breast carcinomas and who had not received any kind of adjuvant chemotherapy or endocrine therapy who were operated from January 1986 to May 1987 were studied. ICAs of tumour specimens were performed in optimal technical conditions (frozen sections, automated immunoperoxidase technique (Ventana), and computer assisted analysis of digitised coloured microscopic images (SAMBA)) to determine cathepsin D immunocytochemical expression. Results of quantitative ICAs were correlated with overall and disease free survival over 8.4 years of follow up in axillary lymph node positive and negative patients. RESULTS: Cathepsin D immunocytochemical expression in tumours of 15% or more was significantly associated with poor overall survival in the whole group and in node positive patients (Kaplan Meier, log rank test p = 0.003 and p = 0.007); however, it was not correlated with survival in node negative patients. Cathepsin D immunocytochemical expression (> 15%) correlated with short disease free (p = 0.015) and short recurrence free survival (p = 0.021) in the group as a whole but not when node positive and negative patients were evaluated separately. CONCLUSIONS: In optimal conditions (automated and quantitative ICAs on frozen sections) cathepsin D immunohistochemical expression is a significant prognostic indicator in terms of overall, disease free, and recurrence free survival; however, there is no correlation when node negative patients are considered separately.

Adult↗

PubMed1996

Quantitative immunocytochemical assays on frozen sections of p53: correlation to the follow-up of patients with breast carcinomas.

A series of 222 tumor samples stored at -80 degrees C in the authors' tumor library were investigated with anti-p53 (PA 1801) and streptavidin-biotin-peroxidase complex. The p53 immunoprecipitates were quantified by densitometry assessed by image analysis of digitized microscopic images. Two parameters, percentage of positive surface and mean optical densities, were compared with the patient's outcome (follow-up = 96.8 months) (life table method, Mantel Cox test, BMDP statistical software). The p53 expression significantly correlated with a poor overall survival (P = .0063), metastasis-free survival (P = .024), and recurrence-free survival (P = .022) at a 20% cutoff point of positive immunoreactive tumor surface. A strong prognostic significance was observed in the node-positive subset of patients but not in the node-negative subset, except for recurrence-free survival (P = .047). The results indicate the clinical relevance p53 evaluated by quantitative immunocytochemistry.

Adult↗

PubMed1995

p53 quantitative immunocytochemical analysis in breast carcinomas.

A series of 200 breast carcinomas was investigated on frozen sections using PAb 1801 p53 monoclonal antibody and streptavidin biotin peroxidase complex. Densitometric analysis of the immunoprecipitates was assessed by processing digitized microscopic images. p53 was observed in the nucleus of 48% of the tumors. Some tumors (14 of 91) tested in parallel on paraffin sections were negative, although positive on frozen sections. Image analysis showed that the surfaces positive with anti-p53 and the staining intensity were decreased (P < .01) on paraffin sections. The p53 tumor expression was independent of patient age, tumor size, axillary lymph node status, HER-2/neu and cathepsin D expression, and nuclear morphometric parameters. However, p53 correlated with high histological grade (P < .01), lack of estrogen receptor (ER) (P = .0015) and progesterone (PR) (P = .0065) antigenic sites, pS2 detection (P = .03), high Ki-67 immunoreactivity (P = .018), large silver-stained nucleolar organizer region (AgNOR) nuclear surface ratio (P < .02), and degree of hyperploidy (P < .03), and was more often observed in the comedocarcinomas. The results suggest that p53 expression in breast carcinomas is not a totally independent prognostic indicator and that the clinical relevance and prognostic significance of p53 expression in breast carcinomas can be reliably assessed provided that the procedures are standardized, particularly with regard to the use of frozen sections and image analysis processing of the immunodetection.

Adult↗