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Histopathology Apr 2024Tumour protein 63 (p63) is a transcription factor of the p53 gene family, encoded by the TP63 gene located at chromosome 3q28, which regulates the activity of genes... (Review)
Review
Tumour protein 63 (p63) is a transcription factor of the p53 gene family, encoded by the TP63 gene located at chromosome 3q28, which regulates the activity of genes involved in growth and development of the ectoderm and derived tissues. p63 protein is normally expressed in the nuclei of the basal cell layer of glandular organs, including breast, in squamous epithelium and in urothelium. p63 immunohistochemical (IHC) staining has several applications in diagnostic breast pathology. It is commonly used to demonstrate myoepithelial cells at the epithelial stromal interface to differentiate benign and in situ lesions from invasive carcinoma and to characterize and classify papillary lesions including the distinction of breast intraduct papilloma from skin hidradenoma. p63 IHC is also used to identify and profile lesions showing myoepithelial cell and/or squamous differentiation, e.g. adenomyoepithelioma, salivary gland-like tumours including adenoid cystic carcinoma, and metaplastic breast carcinoma including low-grade adenosquamous carcinoma. This article reviews the applications of p63 IHC in diagnostic breast pathology and outlines a practical approach to the diagnosis and characterization of breast lesions through the identification of normal and abnormal p63 protein expression. The biology of p63, the range of available antibodies with emphasis on staining specificity and sensitivity, and pitfalls in interpretation are also discussed. The TP63 gene in humans, which shows a specific genomic structure, resulting in either TAp63 (p63) isoform or ΔNp63 (p40) isoform. As illustrated in the figure, both isoforms contain a DNA-binding domain (Orange box) and an oligomerization domain (Grey box). TAp63 contains an N-terminal transactivation (TA) domain (Green box), while ΔNp63 has an alternative terminus (Yellow box). Antibodies against conventional pan-p63 (TP63) bind to the DNA binding domain common to both isoforms (TAp63 and p40) and does not distinguish between them. Antibodies against TAp63 bind to the N-terminal TA domain, while antibodies specific to ΔNp63 (p40) bind to the alternative terminus. Each isoform has variant isotypes (α, β, γ, δ, and ε).
Topics: Female; Humans; Breast Neoplasms; DNA; Immunohistochemistry; Protein Isoforms; Animals; Tumor Suppressor Proteins; Breast
PubMed: 38012539
DOI: 10.1111/his.15101 -
Medical Sciences (Basel, Switzerland) Sep 2023Adenomyoepithelioma (AME) of the breast and gastrointestinal stromal tumors (GISTs) are rare benign (primarily) tumors observed in the breast and gastrointestinal tract,...
Adenomyoepithelioma (AME) of the breast and gastrointestinal stromal tumors (GISTs) are rare benign (primarily) tumors observed in the breast and gastrointestinal tract, respectively. The coexistence of both of these rare tumors is extremely rare; therefore, the author describes the clinical presentation and pathophysiological findings of such a unique case in this study. A 56-year-old female patient with no medical history presented with a substantial right breast lump, severe nausea, and vomiting, and suffered from iron deficiency anemia. Radiological observation and a right breast excisional biopsy diagnosed the patient with AME associated with ductal carcinoma in situ (DCIS). Endoscopy and a CT scan of the stomach revealed the existence of GIST. This is the first reported case of concurrence of a huge mass of AME and GIST in a patient. Histological and immunohistochemistry tests using p63, SMA, calponin, and Ki67 markers for the breast tumor and DOG-1, CD34, and CD117 markers for the gastric tumor revealed the non-invasive benign state. The patient had a right breast mastectomy with a negative resection margin. AME of the breast and GIST pose diagnostic challenges due to their erratic morphological characteristics and can cause misinterpretation drawn solely from radiological tests. Effective and accurate diagnostics require assessing the histological and immunohistochemistry findings of the tumor to identify the invasiveness of the neoplasm and the associated risk levels. This report, thus, creates awareness among clinicians and pathologists for the consideration of such possibilities and, therefore, conducts the necessary diagnostics and prophylactic treatments.
PubMed: 37755162
DOI: 10.3390/medsci11030057 -
Cancers Aug 2023A better understanding of the mechanisms generating tumour heterogeneity will allow better targeting of current therapies, identify potential resistance mechanisms and...
A better understanding of the mechanisms generating tumour heterogeneity will allow better targeting of current therapies, identify potential resistance mechanisms and highlight new approaches for therapy. We have previously shown that in genetically modified mouse models carrying conditional oncogenic alleles, mammary tumour histotype varies depending on the combination of alleles, the cell type to which they are targeted and, in some cases, reproductive history. This suggests that tumour heterogeneity is not a purely stochastic process; rather, differential activation of signalling pathways leads to reproducible differences in tumour histotype. We propose the NOTCH signalling pathway as one such pathway. Here, we have crossed conditional knockout or alleles into an established mouse mammary tumour model. deletion had no effect on tumour-specific survival; however, loss of alleles resulted in a dose-dependent increase in metaplastic adenosquamous carcinomas (ASQCs). ASQCs and adenomyoepitheliomas (AMEs) also demonstrated a significant increase in AKT signalling independent of status. Therefore, the NOTCH pathway is a suppressor of the ASQC phenotype, while increased PI3K/AKT signalling is associated with ASQC and AME tumours. We propose a model in which PI3K/AKT and NOTCH signalling act interact to determine mouse mammary tumour histotype.
PubMed: 37686600
DOI: 10.3390/cancers15174324 -
ANZ Journal of Surgery Dec 2023
Topics: Humans; Female; Adenomyoepithelioma; Breast; Neoplasms; Breast Neoplasms
PubMed: 37641233
DOI: 10.1111/ans.18676 -
International Journal of Surgery Case... Aug 2023Adenomyoepithelial tumors of the breast are very rare tumors comprising of - fibroepithelial and myoepithelial components PRESENTATION OF THE CASE: We present the case...
Adenomyoepithelial tumors of the breast are very rare tumors comprising of - fibroepithelial and myoepithelial components PRESENTATION OF THE CASE: We present the case of a 66 years old lady who presented with a right breast lump 5 cm in size, diagnosed as an atypical adenomyoepithelioma who underwent successful excision and returned two and half years later with a recurrence DISCUSSION: These tumors present a diagnostic dilemma needing histopathology for definitive diagnosis. Recurrence is not uncommon CONCLUSION: Adenomyoepitheliomas demand regular surveillance for early detection of any recurrence.
PubMed: 37557038
DOI: 10.1016/j.ijscr.2023.108632 -
Pathology, Research and Practice Aug 2023We describe an unusual case of multifocal breast adenoid cystic carcinoma (AdCC) with adenomyoepitheliomatous morphology. Most breast AdCCs are unifocal and only four...
We describe an unusual case of multifocal breast adenoid cystic carcinoma (AdCC) with adenomyoepitheliomatous morphology. Most breast AdCCs are unifocal and only four cases of multifocal AdCC have been reported previously, however, to our best knowledge, multifocality in AdCC confirmed by molecular analysis has not been reported, so this report adds to the literature on this unique presentation. An 80-year-old woman presented with a left breast mass at 1 o'clock and non-mass enhancement lesion at 5 o'clock on imaging. Incisional biopsy at 1 o'clock showed AdCC based on histopathological features and MYB rearrangement by fluorescent in situ hybridization (FISH). As AdCC involved the margins and the non-mass enhancing lesion remained, mastectomy was performed. Microscopically, the lesion at 5 o'clock demonstrated multinodularity and a biphasic epithelial-basaloid/myoepithelial pattern. Although histological features resembled adenomyoepithelioma, MYB rearrangement was identified on FISH, so the 5 o'clock lesion was also diagnosed as AdCC showing an adenomyoepitheliomatous pattern. This unusual presentation is a potential diagnostic pitfall, so pathologists should consider AdCC as a possible differential diagnosis of multifocal basaloid breast tumors with adenomyoepitheliomatous features.
PubMed: 37392549
DOI: 10.1016/j.prp.2023.154650 -
Histopathology Sep 2023Breast pathology is a challenging field, and discrepancies in diagnoses exist and can affect patient management. This study aims to review a breast referral practice and...
AIMS
Breast pathology is a challenging field, and discrepancies in diagnoses exist and can affect patient management. This study aims to review a breast referral practice and assess the pattern and frequency of breast lesions sent for an external expert review and evaluate potential impacts on patients' care.
METHODS AND RESULTS
Seven hundred and forty cases that were referred to Nottingham City Hospital for a second opinion between 2019 and 2022 which have slides and reports were retrieved and reviewed. Reasons for referral, initial diagnosis, proffered specialist opinion and any discrepancy or potential impacts of management were assessed. The most frequent entities were papillary lesions (19%), fibroepithelial lesions (17%), invasive carcinomas that were sent for confirmation of the invasive diagnosis or subtyping of the invasive tumour (17%), intraductal epithelial proliferation with atypia (9%) and spindle cell lesions (8%). Other entities included biphasic tumours such as adenomyoepithelioma, as well as vascular and nipple lesions. Few cases were sent for prognostic classification or comments on the management, and in occasional cases no initial diagnosis was offered. After reviewing the cases by the expert pathologists, the initial diagnosis was confirmed or one of the suggested diagnoses was preferred in 79% of cases, including 129 cases (17%) in which the opinion resulted minor changes in the management. Significant changes in the classification of lesions were made in 132 cases (18%) which resulted in significant change in the patient management recommendation. In 14 cases (2%) a final classification was not possible, and further specialist opinion was obtained. Comments on the differential diagnosis and advice on further patient management were provided in most cases.
CONCLUSIONS
This study demonstrates the value of external referral of challenging, rare and difficult to classify breast lesions. It also highlights the most common breast lesions that are likely to be challenging, and specialist opinion can refine their classification to improve patient care.
Topics: Humans; Female; Diagnostic Errors; Referral and Consultation; Diagnosis, Differential; Carcinoma; Nipples; Breast Neoplasms
PubMed: 37356966
DOI: 10.1111/his.14993 -
International Journal of Surgical... Aug 2023
Topics: Humans; Female; Adenomyoepithelioma; Colorectal Neoplasms, Hereditary Nonpolyposis; Breast; Breast Neoplasms
PubMed: 35707990
DOI: 10.1177/10668969221105623