Immunohistochemical detection of p53 protein in mammary carcinoma: An important new independent indicator of prognosis?

doi:10.1016/0046-8177(93)90158-D

Human Pathology

Volume 24, Issue 5, May 1993, Pages 469-476

https://doi.org/10.1016/0046-8177(93)90158-D Get rights and content

Abstract

In an immunohistochemical pilot study of 195 primary breast cancer patients with a 10-year median follow-up we found that patients with carcinomas who express p53 protein in the majority of their tumor cells (19% of the cases) have a considerably worse prognosis than those who do not. The effect of the presence of the protein is seen on disease-free interval (chi-square, 11,69; P < .001), overall survival (chi-square, 19.68; P < .001), and survival after relapse (chisquare, 4.93; P < .02), and is seen in node-negative (chi-square, 6.99; P < .009) and node-positive (chi-square, 13.05; P < .001) patients. Furthermore, the effect is most apparent in patients with infiltrating lobular and grade II infiltrating ductal carcinomas (chi-square, 27.97; P < .001) that have a rather heterogeneous clinical behavior and are difficult to subdivide on the basis of currently available markers. Cox multivariate analysis shows that p53 majority staining is second only to node status in significance of effect on overall survival.

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Inflammatory Breast Cancer (IBC) is a rare and aggressive form of locally advanced breast cancer, classified as stage T4d according to the tumor-node-metastasis staging criteria. This subtype of breast cancer is known for its rapid progression and significantly lower survival rates compared to other forms of breast cancer. Despite its distinctive clinical features outlined by the World Health Organization, the histopathological characteristics of IBC remain not fully elucidated, presenting challenges in its diagnosis and treatment.
Histologically, IBC tumors often exhibit a ductal phenotype, characterized by emboli composed of pleomorphic cells with a high nuclear grade. These emboli are predominantly found in the papillary and reticular dermis of the skin overlaying the breast, suggesting a primary involvement of the lymphatic vessels. The tumor microenvironment in IBC is a complex network involving various cells such as macrophages, monocytes, and predominantly T CD8+ lymphocytes, and elements including blood vessels and extracellular matrix molecules, which play a pivotal role in the aggressive nature of IBC.
A significant aspect of IBC is the frequent loss of expression of hormone receptors like estrogen and progesterone receptors, a phenomenon that is still under active investigation.
Moreover, the overexpression of ERBB2/HER2 and TP53 in IBC cases is a topic of ongoing debate, with studies indicating a higher prevalence in IBC compared to non-inflammatory breast cancer.
This overview seeks to provide a comprehensive understanding of the histopathological features and diagnostic approaches to IBC, emphasizing the critical areas that require further research.
Evaluation of venous thrombosis and tissue factor in epithelial ovarian cancer
2017, Gynecologic Oncology
Citation Excerpt :
A negative control slide with pancreatic cancer was also included with each group of tumor specimens. Three observers (JGC, AEW, CW) blinded to the clinical data and TFMV results, jointly evaluated the TF immunostained slides using a multihead microscope and a modified H-score to determine TF expression by each tumor [25]. For each tumor, the percentage of tumor cells stained at each of three intensities [0 = no staining to 3 = strong staining] was recorded.
Ovarian clear cell carcinoma (OCCC) and high grade serous ovarian cancer (HGSOC) are associated with the highest risk of VTE among patients with epithelial ovarian cancer (EOC). Tissue factor (TF) is a transmembrane glycoprotein which can trigger thrombosis. We sought to evaluate if there is an association between VTE and tumor expression of tissue factor (TF), plasma TF, and microvesicle TF (MV TF) activity in this high-risk population.
We performed a case-control study of OCCC and HGSOC patients with and without VTE. 105 patients who underwent surgery at a tertiary care center between January 1995 and October 2013 were included. Plasma TF was measured with an enzyme-linked immunosorbent assay. A TF-dependent Factor Xa generation assay was used to measure MV TF activity. Immunohistochemical (IHC) analysis was performed to evaluate tumor expression of TF.
35 women with OCCC or HGSOC diagnosed with VTE within 9 months of surgery were included in the case group. Those with VTE had a worse OS, p < 0.0001, with a greater than three-fold increase in risk of death, HR 3.33 (CI 1.75–6.35). There was no significant difference in median plasma TF level or MV TF activity level between patients with and without VTE. OCCC patients had greater expression of TF in their tumors than patients with HGSOC, p < 0.0001.
TFMV activity and plasma TF level were not predictive of VTE in this patient population. Given the extensive expression of TF in OCCC tumors, it is unlikely IHC expression will be useful in risk stratification for VTE in this population.
Association of epithelial-mesenchymal transition and nuclear cofilin with advanced urothelial cancer
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Sections from individual tumors were subjected to immunostaining using specific antibodies against cofilin and E-cadherin (Cell Signaling Technology, Danvers, MA) and N-cadherin (AbCam Cell Signaling, Cambridge, United Kingdom). Immunoreactivity was determined based on “Quick Score” calculated by multiplying staining intensity (on a scale of 1-3) by percentage of tumor cells with positive immunoreactivity [25]. Two blinded reviewers (P. H., D. Z.) independently reviewed 3 nonadjacent fields (×100) per section.
Tumor epithelial cells undergo a morphologic shift through the process of EMT with characteristic loss of cell polarity, conferring invasive and metastatic properties during cancer progression. Signaling by transforming growth factor-β mediates EMT programming and its phenotypic reversal to mesenchymal-epithelial transition. The role of EMT in bladder cancer progression to advanced disease is poorly understood. In this study, we conducted a retrospective analysis of the EMT landscape and actin cytoskeleton remodeling in a series of human bladder cancer specimens. Immunoreactivity for E-cadherin, N-cadherin, and vimentin protein expression was performed toward establishing an EMT signature in human bladder cancer. Serial sections were assessed for the primary regulator of the actin cytoskeleton remodeling and transforming growth factor-β signaling effector, cofilin. Our results demonstrate that EMT induction in clinical bladder cancer specimens is significantly associated with bladder cancer progression to high-grade, invasive disease. Evaluation of expression and cellular localization of the cytoskeleton regulator cofilin revealed a significant association between overexpression of nuclear cofilin with bladder cancer progression. This study is of translational significance in defining the value of EMT signature and cytoskeletal cofilin as potential tumor markers and targetable platforms for the treatment of invasive bladder cancer.
A preliminary investigation of the role of the transcription co-activators YAP/TAZ of the Hippo signalling pathway in canine and feline mammary tumours
2016, Veterinary Journal
Breast cancer is the most common cancer in women worldwide. Cancer metastases are responsible for the high mortality rate. A small but distinct subset of cells, cancer stem cells (CSCs), have the capacity to self-renew, initiate tumour formation, and develop metastases. The CSC content in human breast cancer correlates with the Hippo tumour suppressor signalling pathway. Specifically, the activity of YAP/TAZ, transcription co-activators of the Hippo pathway, sustains the self-renewal and tumour-initiation capacities of CSCs. Little is known about YAP/TAZ in canine and feline mammary tumours, which are very common tumours. The preliminary aim of the study was to investigate the expression of YAP/TAZ in canine and feline mammary tumours by Western blot and immunohistochemistry.
Increased cytoplasmic and nuclear expression of YAP/TAZ was observed in all carcinomas compared to normal tissues, indicating neoplastic deregulation of the Hippo pathway. Nuclear expression significantly increased in grade III (high grade carcinomas) compared to grade I (low grade carcinomas) tumours, suggesting that YAP/TAZ play a role in the increased aggressiveness of these tumours. Moreover, different scoring systems for immunohistochemical analyses were compared and the H index and the Allred scores were the most significant. In conclusion, YAP/TAZ are expressed in aggressive canine and feline mammary tumours as reported in some human cancers. Further studies might better elucidate the role of the Hippo pathway in prognosis and as a target for new therapies. In addition, tumours in dogs and cats may be a useful model to study this pathway.
Application of nanomaterials in the bioanalytical detection of disease-related genes
2015, Biosensors and Bioelectronics
Citation Excerpt :
Therefore, the sensitive and rapid detection of the TP53 gene and its mutations is of great value for predicting the prognosis and outcome of patients with various types of cancer. A variety of methods for measuring the TP53 gene have been reported, including reverse transcription polymerase chain reaction (RT-PCR) (Will et al., 1995), traditional nucleic acid probes (Wang et al., 1997b), electrochemical sensors (Esteban-Fernández de Ávila et al., 2015), fluorescence-based techniques (Behn and Schuermann, 1998), immunostaining (Noguchi et al., 1998; Pardo et al., 2004), immunohistochemistry (Barnes et al. 1993; Henke et al., 1994). Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen, as it is responsible for health problems worldwide (Moellering 2012).
In the diagnosis of genetic diseases and disorders, nanomaterials-based gene detection systems have significant advantages over conventional diagnostic systems in terms of simplicity, sensitivity, specificity, and portability. In this review, we describe the application of nanomaterials for disease-related genes detection in different methods excluding PCR-related method, such as colorimetry, fluorescence-based methods, electrochemistry, microarray methods, surface-enhanced Raman spectroscopy (SERS), quartz crystal microbalance (QCM) methods, and dynamic light scattering (DLS). The most commonly used nanomaterials are gold, silver, carbon and semiconducting nanoparticles. Various nanomaterials-based gene detection methods are introduced, their respective advantages are discussed, and selected examples are provided to illustrate the properties of these nanomaterials and their emerging applications for the detection of specific nucleic acid sequences.
Electrochemical DNA sensor for determination of p53 tumor suppressor gene incorporating gold nanoparticles modification
2013, Fenxi Huaxue/ Chinese Journal of Analytical Chemistry
A novel electrochemical DNA (E-DNA) sensor was designed with incorporating gold nanoparticles on a gold electrode for the determination of p53 tumor suppressor gene. A modified gold nanoparticles (GNPs) was prepared by modifying the GNPs prepared by the in situ potentiostatic deposition method on the gold electrode surface. The surface topography of the gold electrode and GNPs/Au were characterized by field emission scanning electron microscope. The E-DNA sensor was prepared through the self-assembly of a 5′-end thiolated probe DNA onto the surface of GNPs/Au followed by the hybridization of complementary sequence DNA. Cyclic voltammetry and electrochemical impedance spectroscopy were used to investigate each immobilization and hybridization step. By using methylene blue (MB) as an indicator for electrochemical hybridization detection, p53 tumor suppressor gene was quantitatively detected by differential pulse voltammetry (DPV) with the reduction peak current of MB. The increase in electrochemical signal upon hybridization was due to that MB had a higher affinity for dsDNA rather than ssDNA. Under the optimal conditions, the reduction peak current of MB was linearly related to the concentration of p53 tumor suppressor gene from 1.0 to 1000 nM with a detection limit of 0.8 nM (S/N = 3). The relative standard deviation obtained was 3.8%. The E-DNA sensor could differentiate the complete complementary DNA sequence, single-base mismatch DNA sequence and three-base mismatched DNA sequence, indicating a good selectivity.

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Human Pathology

Abstract

References (29)

Overexpression of the c-erb-B-2 oncoprotein in human breast carcinomas: Immunohistological assessment correlates with gene amplification

Lancet

An immunochemical analysis of the human nuclear phosphoprotein p53: New monoclonal antibodies and epitope mapping using recombinant p53

J Immunol Methods

Assessment of response to therapy in advanced breast cancer

Eur J Cancer

The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation

Cell

Human breast cancer: Correlation of relapse and survival with amplification of the HER-2/neu oncogene

Science

An immunohistochemical evaluation of c-erbB-2 expression in human breast carcinoma

Br J Cancer

The p53 tumour suppressor gene

Nature

Analysis of p53 expression in human tumors: An antibody raised against human p53 expressed in Escherichia coli

J Cell Sci

World Health Organization: Histological typing of breast tumors

Tumori

Histological grading and prognosis in breast cancer

Br J Cancer

The measurement of receptors for oestradiol and progesterone in human breast tumors

Non-parametric estimation from incomplete observations

Am Stat Assoc J

Regression models and life tables

J R Stat Soc

p53, Guardian of the genome

Nature

Cited by (245)

Inflammatory breast cancer: An overview about the histo-pathological aspect and diagnosis

Evaluation of venous thrombosis and tissue factor in epithelial ovarian cancer

Association of epithelial-mesenchymal transition and nuclear cofilin with advanced urothelial cancer

A preliminary investigation of the role of the transcription co-activators YAP/TAZ of the Hippo signalling pathway in canine and feline mammary tumours

Application of nanomaterials in the bioanalytical detection of disease-related genes

Electrochemical DNA sensor for determination of p53 tumor suppressor gene incorporating gold nanoparticles modification

Original contributionImmunohistochemical detection of p53 protein in mammary carcinoma: An important new independent indicator of prognosis?

Abstract

Lancet

J Immunol Methods

Eur J Cancer

Cell

Human breast cancer: Correlation of relapse and survival with amplification of the HER-2/neu oncogene

Science

An immunohistochemical evaluation of c-erbB-2 expression in human breast carcinoma

Br J Cancer

The p53 tumour suppressor gene

Nature

Analysis of p53 expression in human tumors: An antibody raised against human p53 expressed in Escherichia coli

J Cell Sci

World Health Organization: Histological typing of breast tumors

Tumori

Histological grading and prognosis in breast cancer

Br J Cancer

The measurement of receptors for oestradiol and progesterone in human breast tumors

Non-parametric estimation from incomplete observations

Am Stat Assoc J

Regression models and life tables

J R Stat Soc

p53, Guardian of the genome

Nature

Original contribution
Immunohistochemical detection of p53 protein in mammary carcinoma: An important new independent indicator of prognosis?