scholarly journals Correlation between p53 Status, DNA Ploidy, Proliferation Rate and Nuclear Morphology in Breast Cancer. An Image Cytometric Study

1997 ◽  
Vol 15 (2) ◽  
pp. 85-97 ◽  
Author(s):  
Katrin Friedrich ◽  
Volker Dimmer ◽  
Gunter Haroske ◽  
Wolfdietrich Meyer ◽  
Franz Theissig ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumour Cell ◽  
Dna Ploidy ◽  
Image Cytometry ◽  
Proliferation Rate ◽  
Cell Populations ◽  
Nuclear Morphology ◽  
Breast Cancers ◽  
P53 Expression ◽  
High Proliferation Rate

The study was designed to detect differences in the nuclear morphology of tumours and tumour cell populations with different p53 expression in correlation with DNA ploidy and proliferation rate. The paraffin sections from routinely processed samples of 88 breast cancers were immunostained with the monoclonal p53‐antibody DO‐1. After localization and evaluation with a scoring system the sections were destained and stained by the Feulgen method. The nuclei were relocated automatically and measured by means of the image cytometry workstation. Significant differences between the tumours and tumour cell populations with different p53 expression were found in the euploid tumours as well as in the aneuploid tumours and in the breast cancers with a high proliferation rate. The breast cancers with a low immunoreactive score (IRS 1–4) differ from the negative cancers as well as from the cancers with a higher immunoreactive score (IRS 5–12). Evaluating the nuclear populations of the p53 positive cancers, there were differences in the features of the chromatin amount and distribution in the groups of the euploid breast cancers and in cancer with a high proliferation rate. In contrast, the nuclear populations of the aneuploid cancers did not show any differences in their nuclear morphology.The results showed the different impacts of the p53 expression, DNA ploidy and the proliferation rate on the nuclear morphology in breast cancer.

scholarly journals Morphological Heterogeneity of p53 Positive and p53 Negative Nuclei in Breast Cancers Stratified by Clinicopathological Variables

1997 ◽  
Vol 14 (2) ◽  
pp. 111-123
Author(s):  
Katrin Friedrich ◽  
Volker Dimmer ◽  
Gunter Haroske ◽  
Wolfdietrich Meyer ◽  
Franz Theissig ◽  
...  
Keyword(s):  
Tumour Progression ◽  
Tumour Size ◽  
Image Cytometry ◽  
Lymph Node Status ◽  
Nuclear Morphology ◽  
Breast Cancers ◽  
Biological Behaviour ◽  
P53 Expression ◽  
Morphological Heterogeneity ◽  
P53 Immunohistochemistry

The study was aimed to detect differences in nuclear morphology between nuclear populations as well as between tumours with different p53 expression in breast cancers with different clinicopathological features, which also reflect the stage of tumour progression. The p53 immunohistochemistry was performed on paraffin sections from 88 tumour samples. After the cells had been localised by means of an image cytometry workstation and their immunostaining had been categorised visually, the sections were destained and stained by the Feulgen protocol. The nuclei were relocated and measured cytometrically by the workstation.There were significant differences in the nuclear features between tumours as well as between nuclear populations with different p53 expression in the most subgroups. The variability of nuclear shape in tumour groups, classified by the tumour size or the lymph node status, increase with the p53 immunoreactive score, whereas in tumours grouped by the Bloom–Richardson grade features of the chromatin distribution were different between the p53 staining categories.The nuclear subpopulations showed differences in the amount and distribution of chromatin in most subgroups.The results demonstrate the relationship between the nuclear morphology and the p53 expression in different stages of breast cancers. The p53 status is an important factor of the biological behaviour but not the only one.

p53 and bcl-2 expression correlates with clinical outcome in a series of node-positive breast cancer patients.

1996 ◽  
Vol 14 (5) ◽  
pp. 1604-1610 ◽  
Author(s):  
R Silvestrini ◽  
E Benini ◽  
S Veneroni ◽  
M G Daidone ◽  
G Tomasic ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Outcome ◽  
Mitochondrial Protein ◽  
Axillary Node ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Prognostic Information ◽  
P53 Overexpression ◽  
P53 Expression ◽  
Node Positive

BACKGROUND AND PURPOSE The tumor-suppressor gene TP53 and the proto-oncogene bcl-2 encode, respectively, for a nuclear phosphoprotein and for a mitochondrial protein involved in multiple cellular functions. The proteins provide prognostic information in node-negative breast cancer and are supposed to influence treatment responsiveness. We analyzed the predictive role of p53 and bcl-2 expression, alone and in association with other variables, in postmenopausal women with node-positive, estrogen receptor-positive (ER+) breast cancers treated with radical or conservative surgery plus radiotherapy and adjuvant tamoxifen for at least 1 year. PATIENTS AND METHODS On 240 resectable cancers, we determined the expression of p53 and bcl-2, using immunohistochemistry, cell proliferation (3H-thymidine labeling index [3H-dT LI]), and ER and progesterone receptors (PgR). RESULTS p53 expression and 3H-dT LI were weakly related to one another and both were unrelated to bcl-2. Relapse-free and distant metastasis-free survival at 5 years were significantly lower for patients with tumors that highly expressed p53 (P = .0001) and for those that weakly expressed or did not express bcl-2 (P = .02). However, p53, but not bcl-2, provided prognostic information independent of tumor size, axillary node involvement, steroid receptors, and 3H-dT LI. Moreover, the simultaneous p53 overexpression and lack of PgR identified patients at maximum risk of relapse, whereas bcl-2 overexpression, associated with a low 3H-dT LI or the presence of PgR, improved the prognostic resolution for low-risk patients. CONCLUSION p53 expression appears to be indicative of clinical outcome in postmenopausal patients treated with tamoxifen. Whether p53 overexpression and weak bcl-2 expression are indicators of biologic aggressiveness, regardless of treatment, or of hormone resistance remains to be defined.

scholarly journals The scaffold protein p140Cap limits ERBB2-mediated breast cancer progression interfering with Rac GTPase-controlled circuitries

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Silvia Grasso ◽  
Jennifer Chapelle ◽  
Vincenzo Salemme ◽  
Simona Aramu ◽  
Isabella Russo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Tumour Cell ◽  
Epithelial Mesenchymal Transition ◽  
Predictive Biomarker ◽  
Lower Probability ◽  
Breast Cancers ◽  
Rac Gtpase ◽  
Mesenchymal Transition ◽  
Major Mechanism

Abstract The docking protein p140Cap negatively regulates tumour cell features. Its relevance on breast cancer patient survival, as well as its ability to counteract relevant cancer signalling pathways, are not fully understood. Here we report that in patients with ERBB2-amplified breast cancer, a p140Cap-positive status associates with a significantly lower probability of developing a distant event, and a clear difference in survival. p140Cap dampens ERBB2-positive tumour cell progression, impairing tumour onset and growth in the NeuT mouse model, and counteracting epithelial mesenchymal transition, resulting in decreased metastasis formation. One major mechanism is the ability of p140Cap to interfere with ERBB2-dependent activation of Rac GTPase-controlled circuitries. Our findings point to a specific role of p140Cap in curbing the aggressiveness of ERBB2-amplified breast cancers and suggest that, due to its ability to impinge on specific molecular pathways, p140Cap may represent a predictive biomarker of response to targeted anti-ERBB2 therapies.

Nuclear DNA content, proliferative activity, and p53 expression related to clinical and histopathologic features in endometrial carcinoma

2002 ◽  
Vol 12 (1) ◽  
pp. 110-118 ◽  
Author(s):  
C Lundgren ◽  
G Auer ◽  
B Frankendal ◽  
B Moberger ◽  
B Nilsson ◽  
...  
Keyword(s):  
Endometrial Carcinoma ◽  
Proliferative Activity ◽  
Nuclear Dna ◽  
Dna Ploidy ◽  
Nuclear Dna Content ◽  
Image Cytometry ◽  
P53 Expression ◽  
Degree Of Differentiation ◽  
Histopathologic Features ◽  
Mib 1

Abstract.Lundgren C, Auer G, Frankendal B, Moberger B, Nilsson B, Nordström B. Nuclear DNA content, proliferative activity, and p53 expression related to clinical and histopathologic features in endometrial carcinoma.The purpose of this study was to evaluate the prognostic impact of image cytometry DNA ploidy, MIB-1, and p53 in relation to clinicopathologic variables in 376 consecutive patients with endometrial carcinoma stages I–IV. Following primary treatment 358 patients were considered tumor-free. Relapses and tumor-specific deaths of these patients were noted. Image cytometry DNA ploidy (n = 340) and expression of MIB-1 (n = 318) and p53 (n = 323) were studied. In univariate analysis, stage (P < 0.001), histopathologic subtype (P < 0.001), degree of differentiation (P < 0.001), HRT (P = 0.034), DNA ploidy (P < 0.001), and p53 (P < 0.001) were significant predictors of relapse. Patient age showed that the estimated mean risk of relapse increases with nearly 64% per decade in life (P 0.003), and the MIB-1 expression with 21% per 10-unit increment (P 0.004). In multivariate analysis, degree of differentiation, MIB-1, and p53 lost their prognostic capability. However, after stage and histopathologic subtype, image cytometry DNA ploidy was the strongest predictor of outcome and was of value in predicting the risk for relapse. The combination of DNA ploidy, MIB-1, and p53 expression was an even stronger predictor of relapse-free survival than the individual prognostic factors.

Expression of PTEN, Akt, MAPK, p53, p95 for predicting trastuzumab resistance in breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11088-e11088
Author(s):  
Berna Bozkurt Duman ◽  
Berksoy Sahin ◽  
Melek Ergin ◽  
Suzan Zorludemir ◽  
Arbil Acikalin
Keyword(s):  
Breast Cancer ◽  
Locally Advanced ◽  
Suppressor Gene ◽  
Immunohistochemical Method ◽  
Breast Cancers ◽  
Trastuzumab Resistance ◽  
Her2 Positive ◽  
Tissue Samples ◽  
P53 Expression ◽  
Significant Difference

e11088 Background: The activation of the oncogene PIK3CA and the loss of the tumor suppressor gene PTEN are mutations commonly found in breast tumors. AKT is a key activator of cell survival mechanisms. Mutant p53 proteins can actively contribute to tumorigenesis. Trastuzumab in particular are the primary treatment in the adjuvant and recurrent settings for breast cancer. Many studies reported that selected patients may present with resistance to trastuzumab due to the presence of p95 HER2 fragments. To address this challenge,we analyzied PTEN, Akt, MAPK, p53, p95expressions in breast cancer treated with trastuzumab therapy. . Methods: Ninety patients were assessed for this study and in the guidance of inclusion and exclusion criteria 25 patients were enrolled to the study. HER2 positivite, metastatic or locally advanced patients were enrolled to the study.. All of the patients that included to the study were treated with trastuzumab. Trastusumab resistance was assessed. Antracylin and taxane containing regimens were given to all patients. Gemcitabine, cisplatine capectabine, navelbine containing regimens were given on second and third line treatment choices. Tissue samples were obtained from parafine blocks and evaluated for PTEN, Akt, mapk, p53, p95 expression with immunohistochemical method. Results: The median age was 54±12. PTEN, Akt, MAPK, p53, p95 expressions were found in different levels on tumor tissue samples. Trastuzumab resistance were detected in 5 (20%) patients. Akt expression was positive in 2(8%) patients, MAPK expression was positive in 1 (4%) patient, p95 expression was positive in 1 (4%) patient, p53 expression was positive in 1 (4%) patient, PTEN expression was negative 3 (12%). Statistically significant difference was not found between trastuzumab resistance and PTEN, Akt, MAPK, p53, p95 expressions (respectively p:0,11, 0,79, 0,95, 0,88, 0,74). Conclusions: PTEN, Akt, MAPK, p53, p95expressions were assessed on HER2 positive breast cancers for predicting trastuzumab resistance. There was no statistically significant correlations between trastuzumab resistance and the expressions of these biomarkers. This study is ongoing, this is the preliminary results of this study.

scholarly journals Clinical Significance of Epigenetic Inactivation of hMLH1 and BRCA1 in Tunisian Patients with Invasive Breast Carcinoma

2009 ◽  
Vol 2009 ◽  
pp. 1-7 ◽  
Author(s):  
Sondes Karray-Chouayekh ◽  
Fatma Trifa ◽  
Abdelmajid Khabir ◽  
Nouredine Boujelbane ◽  
Tahia Sellami-Boudawara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Carcinoma ◽  
Gene Promoter ◽  
Disease Free Survival ◽  
Methylation Pattern ◽  
Tumour Suppressor Genes ◽  
Breast Cancers ◽  
Promoter Regions ◽  
P53 Expression ◽  
Tunisian Patients

Aberrant hypermethylation of gene promoter regions is one of the mechanisms for inactivation of tumour suppressor genes in many human cancers including breast carcinoma. In the current study, we aimed to assess by MSP, the methylation pattern of two cancer-related genes involved in DNA repair: hMLH1 (mutL homolog 1,colon cancer,nonpolyposis type 2(E. coli) and BRCA1 (breast cancer 1,early onset) in 78 primary breast cancers from Tunisian patients. The methylation frequencies were 24.36% for hMLH1 and 46% for BRCA1. BRCA1 methylation correlated with age at diagnosis (P=.015) and 5-years disease free survival (P=.016) while hMLH1 methylation was more frequent in larger tumors (P=.002) and in presence of distant metastasis (P=.004). Furthermore, methylation of hMLH1 significantly correlated with high level of P53 expression (P=.006) and with overall survival (P=.015) suggesting that silencing of hMLH1 through aberrant promoter methylation could be used as a poor prognosis indicator in breast cancer.

p53 expression measured by flow cytometry. A comparison of three monoclonal antibodies and the relationship with grade and DNA ploidy in breast cancer

1995 ◽  
Vol 41 (3) ◽  
pp. 146-150 ◽  
Author(s):  
Ian Brotherick ◽  
Brian K. Shenton ◽  
William K. Cowan ◽  
Brian Angus ◽  
Charles H. W. Horne ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Flow Cytometry ◽  
Monoclonal Antibodies ◽  
Dna Ploidy ◽  
P53 Expression ◽  
The Relationship

scholarly journals DNA Ploidy and Chromosomal Imbalances in Invasive Ductal Breast Cancer. A Comparative Study of DNA Image Cytometry and Comparative Genomic Hybridization (CGH)

2000 ◽  
Vol 20 (2-3) ◽  
pp. 69-82 ◽  
Author(s):  
Katrin Friedrich ◽  
Jens Scheithauer ◽  
Volker Dimmer ◽  
Wolfdietrich Meyer ◽  
Franz Theissig ◽  
...  
Keyword(s):  
Genetic Background ◽  
Dna Ploidy ◽  
Image Cytometry ◽  
Comparative Genomic ◽  
Breast Cancers ◽  
Chromosomal Imbalances ◽  
Invasive Ductal Breast Cancer ◽  
Ductal Breast Cancer ◽  
Dna Image Cytometry

Chromosomal imbalances were analyzed in 62 breast cancers with different DNA ploidy by CGH. The results of DNA image cytometry and CGH are consistent with peridiploid and aneuploid cases. The peritetraploid tumors harbored a high number of chromosomal imbalances, as a hint for an unfavorable prognosis. The quantitative analysis of imbalances highlighted the role of different physical constituents of the chromosome, and of chromosomal losses in different DNA ploidy groups. The peritetraploid and aneuploid tumors differed from the peridiploid tumors in losses at 8p and 18q. The peritetraploid cancers exhibited more gains at 8q, the aneuploid tumors more losses at 17p than their peridiploid counterparts. The aneuploid cases differed from the peritetraploid tumors in a higher number of losses at 11q and 14q. Combinations of imbalances provide further insights into the genetic background of DNA ploidy. Hypotheses for the progression from peridiploid to nondiploid breast cancers are given.Figures onhttp://www.esacp.org/acp/2000/20-2_3/friedrich.htm.

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