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Cancers May 2022The gain-of-function mutation in the pleckstrin homology domain of AKT1 (AKT1E17K) occurs in lung and breast cancer. Through the use of human cellular models and of a...
The gain-of-function mutation in the pleckstrin homology domain of AKT1 (AKT1E17K) occurs in lung and breast cancer. Through the use of human cellular models and of a AKT1E17K transgenic Cre-inducible murine strain (R26-AKT1E17K mice), we have demonstrated that AKT1E17K is a bona fide oncogene for lung epithelial cells. However, the role of AKT1E17K in breast cancer remains to be determined. Here, we report the generation and the characterization of a MMTV-CRE; R26-AKT1E17K mouse strain that expresses the mutant AKT1E17K allele in the mammary epithelium. We observed that AKT1E17K stimulates the development of mammary tumors classified as ductal adenocarcinoma of medium-high grade and presented a variety of proliferative alterations classified as adenosis with low-to-high grade dysplasia in the mammary epithelium. A subsequent immunohistochemical characterization suggested they were PR/HER2/ER, basal-like and CK8/CK10/CK5/CK14. We also observed that, in parallel with an increased proliferation rate, tumors expressing mutant AKT1E17K presented an activation of the GSK3/cyclin D1 pathway in the mammary epithelium and cluster significantly with the human basal-like tumors. In conclusion, we demonstrate AKT1E17K is a bona fide oncogene that can initiate tumors at high efficiency in murine mammary epithelium in vivo.
PubMed: 35681625
DOI: 10.3390/cancers14112645 -
Head and Neck Pathology Jul 2013Low-grade salivary duct carcinoma (LG-SDC) is a rare neoplasm characterized by predominant intraductal growth, luminal ductal phenotype, bland microscopic features, and... (Review)
Review
Low-grade salivary duct carcinoma (LG-SDC) is a rare neoplasm characterized by predominant intraductal growth, luminal ductal phenotype, bland microscopic features, and favorable clinical behavior with an appearance reminiscent of florid to atypical ductal hyperplasia to low grade intraductal breast carcinoma. LG-SDC is composed of multiple cysts, cribriform architecture with "Roman Bridges", "pseudocribriform" proliferations with floppy fenestrations or irregular slits, micropapillae with epithelial tufts, fibrovascular cores, and solid areas. Most of the tumor cells are small to medium sized with pale eosinophilic cytoplasm, and round to oval nuclei, which may contain finely dispersed or dark condensed chromatin. Foci of intermediate to high grade atypia, and invasive carcinoma or micro-invasion have been reported in up to 23 % of cases. The neoplastic cells have a ductal phenotype with coexpression of keratins and S100 protein and are surrounded by a layer of myoepithelial cells in non-invasive cases. The main differential diagnosis of LG-SDC includes cystadenoma, cystadenocarcinoma, sclerosing polycystic adenosis, salivary duct carcinoma in situ/high-grade intraductal carcinoma, and papillary-cystic variant of acinic cell carcinoma. There is no published data supporting the continuous classification of LG-SDC as a variant of cystadenocarcinoma. Given that most LG-SDC are non-invasive neoplasms; the terms "cribriform cystadenocarcinoma" and LG-SDC should be replaced by "low-grade intraductal carcinoma" (LG-IDC) of salivary gland or "low-grade intraductal carcinoma with areas of invasive carcinoma" in those cases with evidence of invasive carcinoma.
Topics: Biomarkers, Tumor; Carcinoma in Situ; Humans; Immunohistochemistry; Neoplasm Grading; Salivary Ducts; Salivary Gland Neoplasms
PubMed: 23821212
DOI: 10.1007/s12105-013-0460-1 -
Cancer Cell International Aug 2009NUCKS (Nuclear, Casein Kinase and Cyclin-dependent Kinase Substrate) is a nuclear, DNA-binding and highly phosphorylated protein. A number of reports show that NUCKS is...
BACKGROUND
NUCKS (Nuclear, Casein Kinase and Cyclin-dependent Kinase Substrate) is a nuclear, DNA-binding and highly phosphorylated protein. A number of reports show that NUCKS is highly expressed on the level of mRNA in several human cancers, including breast cancer. In this work, NUCKS expression on both RNA and protein levels was studied in breast tissue biopsies consisted of invasive carcinomas, intraductal proliferative lesions, benign epithelial proliferations and fibroadenomas, as well as in primary cultures derived from the above biopsies. Specifically, in order to evaluate the level of NUCKS protein in correlation with the histopathological features of breast disease, immunohistochemistry was employed on paraffin sections of breast biopsies of the above types. In addition, NUCKS expression was studied by means of Reverse Transcription PCR (RT-PCR), real-time PCR (qRT-PCR) and Western immunoblot analyses in the primary cell cultures developed from the same biopsies.
RESULTS
The immunohistochemical Results showed intense NUCKS staining mostly in grade I and II breast carcinomas compared to normal tissues. Furthermore, NUCKS was moderate expressed in benign epithelial proliferations, such as adenosis and sclerosing adenosis, and highly expressed in intraductal lesions, specifically in ductal carcinomas in situ (DCIS). It is worth noting that all the fibroadenoma tissues examined were negative for NUCKS staining. RT-PCR and qRT-PCR showed an increase of NUCKS expression in cells derived from primary cultures of proliferative lesions and cancerous tissues compared to the ones derived from normal breast tissues and fibroadenomas. This increase was also confirmed by Western immunoblot analysis. Although NUCKS is a cell cycle related protein, its expression does not correlate with Ki67 expression, neither in tissue sections nor in primary cell cultures.
CONCLUSION
The results show overexpression of the NUCKS protein in a number of non malignant breast lesions and cancerous tissues. In particular, the NUCKS overexpression in ADH and DCIS indicates a significant role of this protein in neoplastic progression.
PubMed: 19664271
DOI: 10.1186/1475-2867-9-19 -
Head and Neck Pathology Jun 2012A 25-year-old female presented with a well-defined, painless mass of 1 year's duration in the right parotid gland. MR imaging revealed a relatively well-circumscribed...
A 25-year-old female presented with a well-defined, painless mass of 1 year's duration in the right parotid gland. MR imaging revealed a relatively well-circumscribed lesion involving the deep and superficial lobes of the right parotid gland. Histologic examination of the resection resulted in a diagnosis of sclerosing polycystic adenosis, a rare benign salivary gland entity of presumed non-neoplastic origin. The clinical, radiographic, and morphologic features of sclerosing polycystic adenosis are discussed.
Topics: Adult; Cysts; Female; Humans; Parotid Diseases; Parotid Gland; Sclerosis
PubMed: 22183766
DOI: 10.1007/s12105-011-0317-4 -
Yonsei Medical Journal Jun 1990Fibrocystic disease of the breast has been generally regarded as a disorder due to either excess hormonal stimulation or an exaggerated proliferative response by...
Fibrocystic disease of the breast has been generally regarded as a disorder due to either excess hormonal stimulation or an exaggerated proliferative response by hypersensitive breast epithelium. The unique lobular lesion-adenosis- and its variants have been regarded as non-neoplastic and non-preneoplastic glandular hypertrophy and hyperplasia, and have different organoid patterns and origins. We have examined a total of 242 cases previously diagnosed as 'fibrocystic disease' at the Department of Pathology with the purpose of clarifying the variants of adenosis in detail and refining the infinitely large 'fibrocystic disease' classification as non-proliferative fibrocystic change and proliferative disorders, such as epitheliosis and atypical hyperplasia. In this study, 224 cases (92.5%) were nonproliferative disease, mostly adenosis (40.1%), and 18 cases (7.5%) were proliferative disease, which consisted of moderate to florid hyperplasia and epitheliosis.
Topics: Adult; Breast; Cell Division; Female; Fibrocystic Breast Disease; Fibrosis; Humans; Hyperplasia; Retrospective Studies; Risk Factors
PubMed: 2219974
DOI: 10.3349/ymj.1990.31.2.168 -
Indian Journal of Pathology &... 2024Benign proliferative breast diseases are well recognized in young females. Benign biphasic proliferation of epithelial and myoepithelial cells has been observed, among...
Benign proliferative breast diseases are well recognized in young females. Benign biphasic proliferation of epithelial and myoepithelial cells has been observed, among which adeno-myoepithelial adenosis is one of the rare morphologies published in the literature with the tendency to recur and poses a risk for low-grade malignant transformation. Here, we report a case of a young female who had a history of recurrent breast lump mimicking phyllodes tumor and eventually diagnosed as adeno-myoepithelial adenosis on histopathological examination. Benign proliferative breast diseases are well recognized in young females. Benign biphasic proliferation of epithelial and myoepithelial cells has been observed, among which adeno-myoepithelial adenosis is one of the rare morphologies published in the literature with the tendency to recur and poses a risk for low-grade malignant transformation. Here, we report a case of a young female who had a history of recurrent breast lump mimicking phyllodes tumor and eventually diagnosed as adeno-myoepithelial adenosis on histopathological examination.
Topics: Female; Humans; Phyllodes Tumor; Neoplasm Recurrence, Local; Fibrocystic Breast Disease; Epithelial Cells; Hyperplasia; Cell Transformation, Neoplastic; Breast Neoplasms; Myoepithelioma
PubMed: 38358228
DOI: 10.4103/ijpm.ijpm_925_22 -
Diagnostic Pathology Dec 2022The multistep molecular model of breast carcinogenesis is based on the oestrogen receptor(ER) status of the tumour. Its two main arms comprise ER-positive and...
Proliferative epithelial changes in tumour adjacent tissue in Sri Lankan women with breast carcinoma: do morphological changes support molecular models of breast carcinogenesis?
BACKGROUND
The multistep molecular model of breast carcinogenesis is based on the oestrogen receptor(ER) status of the tumour. Its two main arms comprise ER-positive and ER-negative breast carcinomas(BCa), which are associated with Nottingham grade(NG) of the tumour and different proliferative epithelial changes. According to the model, columnar cell lesions(CCL), lobular carcinoma in-situ(LCIS) and atypical ductal hyperplasia(ADH), low-grade ductal carcinoma in-situ (LG-DCIS) are associated with low grade ER-positive tumours and microglandular adenosis (MGA), pleomorphic LCIS(PLCIS), high-grade DCIS(HG-DCIS) are associated with ER-negative high grade tumours. This study aims to describe the association between proliferative epithelial changes in breast tissue adjacent to tumour, in relation to the ER status and NG of the tumour.
METHODS
This descriptive cross-sectional study included 420, wide local excision and mastectomy specimens of BCa from National Hospital of Sri Lanka, between 2017-2019. The histopathological features of the tumour and proliferative epithelial changes in tumour adjacent tissue within 10 mm distance from the tumour-host interface were evaluated independently by two pathologists. The ER, PR(Progesterone receptor) and HER2 status assessed by immunohistochemistry(IHC) was reviewed. The associations between above epithelial lesions and ER status and NG{categorised as low grade (NG1 and NG2) and high grade (NG3)} of the tumour were analyzed.
RESULTS
ER positive BCa showed significant associations with CCH (p = 0.04), FEA (p = 0.035) and LGDCIS (p < 0.001). Although PLCIS was more frequent in ER positive tumours, the association did not attain statistical significance. ER negative BCa showed a significant association with HGDCIS (p = 0.016). CCLs as a whole (p = 0.005) and also CCC (p = 0.006) and FEA (p = 0.048) and LGDCIS (p < 0.001) showed significant associations with low NG tumours. High NG tumours showed a significant association with HGDCIS (p < 0.001). Microglandular adenosis was not identified in our study population.
CONCLUSION
These morphological findings support the multistep molecular based pathogenetic pathways of breast carcinoma in the studied setting in South Asia. Identification of these proliferative epithelial components in a core biopsy that is negative for BCa, should prompt for close clinicoradiological correlation, and if necessary re-biopsy of women suspected of harbouring a BCa.
Topics: Humans; Female; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Sri Lanka; Cross-Sectional Studies; Mastectomy; Breast Carcinoma In Situ; Carcinogenesis; Carcinoma, Ductal, Breast
PubMed: 36581929
DOI: 10.1186/s13000-022-01281-w -
California Medicine Jul 1973
PubMed: 18730970
DOI: No ID Found -
Histopathology Jan 2016Breast lesions comprise a family of heterogeneous entities with variable patterns of presentation, morphology and clinical behaviour. The majority of breast lesions are... (Review)
Review
Breast lesions comprise a family of heterogeneous entities with variable patterns of presentation, morphology and clinical behaviour. The majority of breast lesions are classified traditionally into benign and malignant conditions and their behaviour can, in the vast majority of cases, be predicted with a reasonable degree of accuracy. However, there remain lesions which show borderline features and lie in a grey zone between benign and malignant, as their behaviour cannot be predicted reliably. Defined pathological categorization of such lesions is challenging, and for some entities is recognized to be subjective and include a range of diagnoses, and forms of terminology, which may trigger over- or undertreatment. The rarity of these lesions makes the acquisition of clinical evidence problematic and limits the development of a sufficient evidence base to support informed decision-making by clinicians and patients. Emerging molecular evidence is providing a greater understanding of the biology of these lesions, but this may or may not be reflected in their clinical behaviour. Herein we discuss some breast lesions that are associated with uncertainty regarding classification and behaviour, and hence management. These include biologically invasive malignant lesions associated with uncertain metastatic potential, such as low-grade adenosquamous carcinoma, low-grade fibromatosis-like spindle cell carcinoma and encapsulated papillary carcinoma. Other lesions of uncertain malignant nature remain, such as mammary cylindroma, atypical microglandular adenosis, mammary pleomorphic adenoma and infiltrating epitheliosis. The concept of categories of (1) breast lesions of uncertain malignant nature and (2) breast lesions of limited metastatic potential are proposed with details of which histological entities could be included in each category, and their management implications are discussed.
Topics: Breast; Breast Neoplasms; Carcinoma; Carcinoma, Adenosquamous; Diagnosis, Differential; Female; Fibroma; Humans
PubMed: 26348644
DOI: 10.1111/his.12861 -
NPJ Breast Cancer 2016Triple-negative breast cancers (TNBCs), defined by lack of expression of estrogen receptor, progesterone receptor and HER2, account for 12-17% of breast cancers and are... (Review)
Review
Triple-negative breast cancers (TNBCs), defined by lack of expression of estrogen receptor, progesterone receptor and HER2, account for 12-17% of breast cancers and are clinically perceived as a discrete breast cancer subgroup. Nonetheless, TNBC has been shown to constitute a vastly heterogeneous disease encompassing a wide spectrum of entities with marked genetic, transcriptional, histological and clinical differences. Although most TNBCs are high-grade tumors, there are well-characterized low-grade TNBCs that have an indolent clinical course, whose natural history, molecular features and optimal therapy vastly differ from those of high-grade TNBCs. Secretory and adenoid cystic carcinomas are two histologic types of TNBCs underpinned by specific fusion genes; these tumors have an indolent clinical behavior and lack all of the cardinal molecular features of high-grade triple-negative disease. Recent studies of rare entities, including lesions once believed to constitute mere benign breast disease (e.g., microglandular adenosis), have resulted in the identification of potential precursors of TNBC and suggested the existence of a family of low-grade triple-negative lesions that, despite having low-grade morphology and indolent clinical behavior, have been shown to harbor the complex genomic landscape of common forms of TNBC, and may progress to high-grade disease. In this review, we describe the heterogeneity of TNBC and focus on the histologic and molecular features of low-grade forms of TNBC. Germane to addressing the challenges posed by the so-called triple-negative disease is the realization that TNBC is merely a descriptive term, and that low-grade types of TNBC may be driven by distinct sets of genetic alterations.
PubMed: 28721389
DOI: 10.1038/npjbcancer.2016.36