scholarly journals Genetic Instability Promotes the Acquisition of Chromosomal Imbalances in T1b and T1c Breast Adenocarcinomas

2001 ◽  
Vol 22 (3) ◽  
pp. 123-131 ◽  
Author(s):  
Harald Blegen ◽  
B. Michael Ghadimi ◽  
Annukka Jauho ◽  
Anders Zetterberg ◽  
Elina Eriksson ◽  
...  
Keyword(s):  
Copy Number ◽  
Proliferative Activity ◽  
Nuclear Dna ◽  
Nuclear Dna Content ◽  
Cyclin A ◽  
Breast Carcinomas ◽  
Ki 67 ◽  
P53 Expression ◽  
Genomic Imbalances ◽  
Copy Number Changes

In order to evaluate biological and genetic properties of early breast carcinomas we analyzed microdissected tissue from 33 primary breast carcinomas stage T1b and T1c with respect to the nuclear DNA content, the expression pattern of Ki‐67, cyclin A, p27KIP1, p53 and p21WAF1, and chromosomal gains and losses. The results show that T1b carcinomas (6–10 mm,n=17) were frequently near‐diploid (53%) with low proliferative activity and staining patterns of p53 and p21WAF1that suggest the presence of wild type protein. The majority (12/16) of the T1c tumors (11–20 mm), however, was aneuploid, and proliferative activity and p53 expression were increased. Larger tumor size correlated with an increasing number of chromosomal copy number changes and in particular with regional amplifications. High level copy number increases (amplifications), however, were found exclusively in the aneuploid tumors. Amplification events correlated with elevated cyclin A and reduced p27 expression, respectively. Our results suggest that the sequential acquisition of genomic imbalances during tumor progression is accelerated in aneuploid tumors, and may contribute to the increased malignancy potential.

scholarly journals DNA Amplifications and Aneuploidy, High Proliferative Activity and Impaired Cell Cycle Control Characterize Breast Carcinomas with Poor Prognosis

2003 ◽  
Vol 25 (3) ◽  
pp. 103-114 ◽  
Author(s):  
Harald Blegen ◽  
John S. Will ◽  
B. Michael Ghadimi ◽  
Hesed‐Padilla Nash ◽  
Anders Zetterberg ◽  
...  
Keyword(s):  
Copy Number ◽  
Proliferative Activity ◽  
Distant Metastases ◽  
Comparative Genomic ◽  
Short Term ◽  
Ki 67 ◽  
Chromosomal Copy ◽  
Copy Number Changes ◽  
Long Term Survivors

In order to explore whether specific cytogenetic abnormalities can be used to stratify tumors with a distinctly different clinical course, we performed comparative genomic hybridization (CGH) of tumors from patients who were diagnosed with metastatic disease after an interval of less than 2 years or who remained free from distant metastases for more than 10 years. All patients presented with distant metastases after mastectomy indicating that none of the patients in this study was cured and free of remaining tumor cells. Tumors in the group of short‐term survivors showed a higher average number of chromosomal copy alterations compared to the long‐term survivors. Of note, the number of sub‐chromosomal high‐level copy number increases (amplifications) was significantly increased in the group of short‐term survivors. In both short‐ and long‐term survivors recurrent chromosomal gains were mapped to chromosomes 1q, 4q, 8q, and 5p. Copy number changes that were more frequent in the group of short‐term survivors included gains of chromosome 3q, 9p, 11p and 11q and loss of 17p. Our results indicate that low‐ and high grade malignant breast adenocarcinomas are characterized by a specific pattern of chromosomal copy number changes. Furthermore, immunohistochemical evaluation of the expression levels of Ki‐67, p27KIP1, p21WAF1, p53, cyclin A and cyclin E revealed a correlation between increased proliferative activity and poor outcome.

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.

Immunohistochemical study of p53 expression in endometrial carcinomas: correlation with markers of proliferating cells and clinicopathologic features

1993 ◽  
Vol 3 (6) ◽  
pp. 363-368 ◽  
Author(s):  
T. Hachisuga ◽  
K. Fukuda ◽  
M. Uchiyama ◽  
N. Matsuo ◽  
T. Iwasaka ◽  
...  
Keyword(s):  
Dna Polymerase ◽  
Proliferative Activity ◽  
P53 Protein ◽  
Myometrial Invasion ◽  
Proliferating Cells ◽  
Ki 67 ◽  
Normal Endometrium ◽  
P53 Expression ◽  
Dna Polymerase Α ◽  
Endometrial Carcinomas

Using anti-p53 (PAb1801 and PAb240), anti-DNA polymerase α and Ki-67 monoclonal antibodies, the expression of p53 was studied in 11 normal endometria, 14 endometrial hyperplasias and 27 endometrial carcinomas and its relationship to the proliferative activity of the tumors was examined. Normal endometria and simple hyperplasias were completely negative for p53. The PAb1801 indices of complex hyperplasias and complex atypical hyperplasias were 2.5±1.8% and 5.0±3.2%, respectively. The PAb1801 indices of grade 1, grade 2 and grade 3 endometrial carcinomas were 10.2±14.2%, 44.4±29/0% and 45.0±32.5%, respectively. These results indicate a progressively enhanced p53 expression in the sequence from normal endometrium, through hyperplasia to carcinoma. A significant correlation between p53 expression and labeling indices of Ki-67 and DNA polymerase α was observed in endometrial carcinomas. The endo-metrial carcinomas with p53 overexpression developed mainly in post-menopausal patients and were frequently high-grade tumors with deep myometrial invasion. These findings may indicate that overexpression of p53 protein contributes to the proliferative activity of the tumor cells.

Expression of proliferation genes in formalin-fixed paraffin-embedded (FFPE) tissue from breast carcinomas. Feasibility and relevance for a routine histopathology laboratory

2016 ◽  
Vol 70 (1) ◽  
pp. 25-32 ◽  
Author(s):  
Carla Thomas ◽  
Cleo Robinson ◽  
Ben Dessauvagie ◽  
Benjamin Wood ◽  
Greg Sterrett ◽  
...  
Keyword(s):  
Gene Expression ◽  
Breast Carcinoma ◽  
Expression Profiling ◽  
Proliferative Activity ◽  
Breast Cancers ◽  
Breast Carcinomas ◽  
Ki 67 ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Formalin Fixed

AimBreast carcinoma proliferative activity, histological grade and commercial molecular tests are all important in prognostication and treatment. There is a particular need for improved, standardised techniques for subclassification of grade 2 breast cancers into low-risk and high-risk prognostic groups. In this study we investigated whether gene expression profiling of five proliferation genes was feasible using breast cancer tissue in a clinical setting and whether these profiles could enhance pathological assessment.MethodsExpression of five proliferation gene mRNAs; Ki-67, STK 15, CCNB1, CCND1 and MYBL2, was quantified in 27 breast carcinomas and compared with Ki-67 proliferation index (PI) and Nottingham mitotic score.ResultsExpression of Ki-67, STK15 and MYBL2 mRNA showed moderate Spearman's correlation with Ki-67 PI (p<0.01), but CCND1 and CCNB1 showed weak, non-significant correlation. Individual gene expression did not associate with mitotic score but combined mRNA expression correlated with both Ki-67 PI (p=0.018) and mitotic score (p=0.03; 0.007).ConclusionsThis study confirms mRNA analysis in breast carcinoma formalin-fixed, paraffin-embedded samples is feasible and suggests gene expression profiling, using a small set of five proliferation genes, has potential in aiding histological grading or assessment of proliferative activity of breast cancers. To fully evaluate the clinical applicability of this approach, a larger cohort study with long-term follow-up data is required.

Nuclear DNA content in breast carcinomas with neuroendocrine differentiation

1986 ◽  
Vol 150 (3) ◽  
pp. 181-185 ◽  
Author(s):  
Jahn M. Nesland ◽  
Erik O. Pettersen ◽  
Sophie D. Fosså ◽  
Johan Høsie ◽  
Jan Vincents Johannessen
Keyword(s):  
Dna Content ◽  
Nuclear Dna ◽  
Neuroendocrine Differentiation ◽  
Nuclear Dna Content ◽  
Breast Carcinomas

scholarly journals Genetic Profile of Adenoid Cystic Carcinomas (ACC) with High-Grade Transformation versus Solid Type

2010 ◽  
Vol 33 (5-6) ◽  
pp. 217-228 ◽  
Author(s):  
Ana Flávia Costa ◽  
Albina Altemani ◽  
Hedy Vékony ◽  
Elisabeth Bloemena ◽  
Florentino Fresno ◽  
...  
Keyword(s):  
Copy Number ◽  
Genetic Profile ◽  
High Grade ◽  
Ki 67 ◽  
Genetic Changes ◽  
Genome Wide ◽  
Genetic Complexity ◽  
Poorly Differentiated ◽  
High Grade Transformation ◽  
Copy Number Changes

Background: ACC can occasionally undergo dedifferentiation also referred to as high-grade transformation (ACC-HGT). However, ACC-HGT can also undergo transformation to adenocarcinomas which are not poorly differentiated. ACC-HGT is generally considered to be an aggressive variant of ACC, even more than solid ACC. This study was aimed to describe the genetic changes of ACC-HGT in relation to clinico-pathological features and to compare results to solid ACC.Methods: Genome-wide DNA copy number changes were analyzed by microarray CGH in ACC-HGT, 4 with transformation into moderately differentiated adenocarcinoma (MDA) and two into poorly differentiated carcinoma (PDC), 5 solid ACC. In addition, Ki-67 index and p53 immunopositivity was assessed.Results: ACC-HGT carried fewer copy number changes compared to solid ACC. Two ACC-HGT cases harboured a breakpoint at 6q23, near the cMYB oncogene. The complexity of the genomic profile concurred with the clinical course of the patient. Among the ACC-HGT, p53 positivity significantly increased from the conventional to the transformed (both MDA and PDC) component.Conclusion: ACC-HGT may not necessarily reflect a more advanced stage of tumor progression, but rather a transformation to another histological form in which the poorly differentiated forms (PDC) presents a genetic complexity similar to the solid ACC.

Comparative Study of Ki-67 Immunostaining and Nuclear DNA Content in Histiofibrous Tumors

1992 ◽  
Vol 19 (1) ◽  
pp. 12-18 ◽  
Author(s):  
Mariko Ooe ◽  
Toshitatsu Nogita ◽  
Makoto Kawashima
Keyword(s):  
Comparative Study ◽  
Dna Content ◽  
Nuclear Dna ◽  
Nuclear Dna Content ◽  
Ki 67
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