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 ◽  
...  

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.

1997 ◽  
Vol 15 (2) ◽  
pp. 85-97 ◽  
Author(s):  
Katrin Friedrich ◽  
Volker Dimmer ◽  
Gunter Haroske ◽  
Wolfdietrich Meyer ◽  
Franz Theissig ◽  
...  

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.


Author(s):  
C. Divyapriya ◽  
Aarthi Kannan ◽  
Vijayashree Raghavan

Introduction: Tumor infiltrating lymphocytes (TILs) are widely considered a key sign of the immune interaction between host and tumor, and potentially prognostic biomarkers of good or bad outcome in various cancers, including invasive breast cancer (IBC). Aim and Objectives: To correlate the expression of CD4, CD8 T-lymphocytes in invasive carcinoma breast with established markers of prognosis like tumour size, grade, lymph node status and molecular subtypes mainly ER, PR, Her 2Neu, Ki67 status, mainly the triple negative breast cancers(TNBC). Methodology: 58 Invasive breast carcinoma proven tissue blocks were subjected to immunohistochemistry and morphometric analysis for positive CD4, CD8 T-lymphocytes were done. Results:  Triple negative breast cancer subtype shows high TILs than other pathologic subtypes. Tumor interface CD8+ cells very well correlated with the pathological higher nodal stage. Majority CD4, CD8 positive cells were populated more towards the stromal and interface of the tumor microenvironment rather thatintratumoral. Conclusion: CD4+ and CD8+ counts may be a valuable independent prognostic tool in predicting the outcome in invasive breast cancer.


2016 ◽  
Vol 70 (4) ◽  
pp. 320-326 ◽  
Author(s):  
Syed Salahuddin Ahmed ◽  
Aye Aye Thike ◽  
Kathryn Zhang ◽  
Jeffrey Chun Tatt Lim ◽  
Puay Hoon Tan

AimsThe presence of oestrogen and progesterone receptors (ER, PR) in breast carcinoma is an important prognostic indicator as well as a predictor of likely response to hormonal treatment. Current ambiguity surrounds ER-negative (–)/PR-positive (+) breast cancer (BC) as to whether this phenotype exists as a distinct entity. The independent predictive value of PR for treatment considerations is also in question, as some investigators believe ER status to be the single most important therapeutic predictive factor in BC. We undertook this study to determine the existence of ER(–)/PR(+) BC and the prognostic effect, if any, of this phenotype.MethodsWe investigated 267 archival documented ER(–)/PR(+) BCs diagnosed between January 1994 and July 2009. Histological slides were retrieved and reviewed. Tissue microarrays were constructed by selecting two 1 mm cores of tumour per case. Repeat immunohistochemistry was performed for confirmation of the ER(–)/PR(+) status. Clinicopathological parameters including age, ethnicity, tumour size, histological grade, histological subtype, associated ductal carcinoma in situ, lymphovascular invasion and lymph node status were evaluated.ResultsOn repeat immunohistochemistry, 92 tumours were confirmed as ER(–)/PR(+) BCs. This phenotype accounted for 1.1% of all BC phenotypes and exhibited different clinicopathological features and survival outcome when compared with other phenotypes. ER(–)/PR(+) tumours showed a trend for an early recurrence and poorer overall survival as compared with the patients with ER(+)/PR(+) tumours and similar to ER(–)/PR(–) tumours.ConclusionsOur findings suggest that ER(–)/PR(+) BCs exist, although rare, with distinct pathological and clinical characteristics from patients with ER(+)/PR(+) BCs.


Author(s):  
E. Amiri Souri ◽  
A. Chenoweth ◽  
A. Cheung ◽  
S. N. Karagiannis ◽  
S. Tsoka

Abstract Background Prognostic stratification of breast cancers remains a challenge to improve clinical decision making. We employ machine learning on breast cancer transcriptomics from multiple studies to link the expression of specific genes to histological grade and classify tumours into a more or less aggressive prognostic type. Materials and methods Microarray data of 5031 untreated breast tumours spanning 33 published datasets and corresponding clinical data were integrated. A machine learning model based on gradient boosted trees was trained on histological grade-1 and grade-3 samples. The resulting predictive model (Cancer Grade Model, CGM) was applied on samples of grade-2 and unknown-grade (3029) for prognostic risk classification. Results A 70-gene signature for assessing clinical risk was identified and was shown to be 90% accurate when tested on known histological-grade samples. The predictive framework was validated through survival analysis and showed robust prognostic performance. CGM was cross-referenced with existing genomic tests and demonstrated the competitive predictive power of tumour risk. Conclusions CGM is able to classify tumours into better-defined prognostic categories without employing information on tumour size, stage, or subgroups. The model offers means to improve prognosis and support the clinical decision and precision treatments, thereby potentially contributing to preventing underdiagnosis of high-risk tumours and minimising over-treatment of low-risk disease.


Author(s):  
Laurenz Nagl ◽  
Andreas Seeber ◽  
Gerlig Widmann ◽  
Katja Schmitz ◽  
Herbert Maier ◽  
...  

SummaryPrimary pulmonary sarcomas (PPS) are rare mesenchymal lung cancers, which do not present clinically or radiological different to lung carcinomas. Definite PPS diagnosis can only be made by histological analysis and detailed staging examinations in order to exclude a secondary pulmonary malignancy such as metastatic soft tissue sarcoma or another solid tumour. Here we present the case of a 66-year-old woman with a pulmonary mass infiltrating the diaphragm and the mediastinal adipose tissue, which was identified as leiomyosarcoma. The patient received curative surgery with complete tumour R0 resection. The prognosis of PPS is defined by tumour size, lymph node status and histological grading. Surgery is the mainstay of therapy and there is no definitive indication for adjuvant therapy for R0-resected and lymph-node-negative patients like in our case. However, multimodal therapy approaches such as (neo)adjuvant chemo- and radiotherapy can contribute to improving locoregional tumour control, which is the most important prognostic factor. With our case report we want to raise awareness for pulmonary sarcomas as a relevant proportion of rare lung cancers which have to be kept in mind during the differential diagnosis. Moreover, we aim to discuss the complex and individual interdisciplinary management.


2014 ◽  
Vol 69 (12) ◽  
pp. 1259-1263 ◽  
Author(s):  
R. Mullen ◽  
J.M. Thompson ◽  
O. Moussa ◽  
S. Vinnicombe ◽  
A. Evans

2018 ◽  
Vol 69 (1) ◽  
pp. 24-29 ◽  
Author(s):  
Hae Jin Kim ◽  
Byung Kwan Park ◽  
In Sun Chung

Purpose Percutaneous radiofrequency ablation is so painful that this treatment requires pain control such as conscious sedation or general anesthesia. It is still unclear which type of anesthesia is better for treatment outcomes of renal cell carcinoma. This study aimed to compare general anesthesia and conscious sedation in treating patients with renal cell carcinoma with radiofrequency ablation. Methods Between 2010 and 2015, 51 patients with biopsy-proven renal cell carcinomas (<4 cm) were treated with computed tomography–guided radiofrequency ablation. General anesthesia was performed in 41 and conscious sedation was performed in 10 patients. Tumour size, local tumour progression, metastasis, major complication, effective dose, glomerular filtration rate difference, and recurrence-free survival rate were compared between these groups. Results The mean tumour size was 2.1 cm in both groups ( P = .673). Local tumour progression occurred in 0% (0 of 41) of the general anesthesia group, but in 40% (4 of 10) of the conscious sedation group ( P = .001). Metastases in these groups occurred in 2.4% (1 of 41) of the general anesthesia group and 20% (2 of 10) of the conscious sedation group ( P = .094). No major complications developed in either group after the first radiofrequency ablation session. The mean effective doses in these groups were 21.7 mSv and 21.2 mSv, respectively ( P = .868). The mean glomerular filtration rate differences in the general anesthesia and conscious sedation groups were −13.5 mL/min/1.73 m2 and −19.1 mL/min/1.73 m2, respectively ( P = .575). Three-year recurrence-free survival rates in these groups were 97.6% and 60.0%, respectively ( P = .001). Conclusions General anesthesia may provide better intermediate outcomes than conscious sedation in treating small renal cell carcinomas with radiofrequency ablation.


2019 ◽  
Author(s):  
Alfonso Bolado-Carrancio ◽  
Morwenna Muir ◽  
Ailith Ewing ◽  
Kenneth Macleod ◽  
William Gallagher ◽  
...  

ABSTRACTISG15 is an ubiquitin-like modifier that is associated with reduced survival rates in breast cancer patients. However, the mechanism by which ISG15 achieves this remains elusive. We demonstrate that modification of Rab GDP-Dissociation Inhibitor Beta (GDI2) by ISG15 (ISGylation) alters endocytic recycling of the EGF receptor (EGFR). By regulating EGFR trafficking, ISGylation sustains Akt-signalling in vitro and in vivo. Persistent and enhanced Akt activation explains the more aggressive tumour behaviour observed in animal models and human breast cancers. We show that ISGylation can act as driver of tumour progression rather than merely being a marker of it.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Raíssa Pinheiro de Mendonça ◽  
Karolyny Martins Balbinot ◽  
Beatriz Voss Martins ◽  
Maria Sueli da Silva Kataoka ◽  
Ricardo Alves Mesquita ◽  
...  

Abstract Ameloblastomas are epithelial odontogenic tumours that, although benign, are locally invasive and may exhibit aggressive behaviour. In the tumour microenvironment, the concentration of oxygen is reduced, which leads to intratumoral hypoxia. Under hypoxia, the crosstalk between the HIF-1α, MMP-2, VEGF, and VEGFR-2 proteins has been associated with hypoxia-induced angiogenesis, leading to tumour progression and increased invasiveness. This work showcases 24 ameloblastoma cases, 10 calcifying odontogenic cysts, and 9 dental follicles, used to investigate the expression of these proteins by immunohistochemistry. The anti-HIF-1α, anti-MMP-2, anti-VEGF, and anti-VEGFR-2 primary antibodies are used in this work. The results have been expressed by the mean grey value after immunostaining in images acquired with an objective of 40×. The ameloblastoma samples showed higher immunoexpression of HIF-1α, MMP-2, VEGF, and VEGFR-2 when compared to the dental follicles and calcifying odontogenic cysts. Ameloblastomas show a higher degree of expression of proteins associated with intratumoral hypoxia and proangiogenic proteins, which indicates the possible role of these proteins in the biological behaviour of this tumour.


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