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Breast Cancer Research and Treatment Dec 2023Low-grade adenosquamous carcinoma (LGASC) is a rare type of metaplastic carcinoma of the breast (MBC) with an indolent clinical course. A few LGASC cases with high-grade...
PURPOSE
Low-grade adenosquamous carcinoma (LGASC) is a rare type of metaplastic carcinoma of the breast (MBC) with an indolent clinical course. A few LGASC cases with high-grade transformation have been reported; however, the genetics underlying malignant progression of LGASC remain unclear.
METHODS
We performed whole-genome sequencing analysis on five MBCs from four patients, including one case with matching primary LGASC and a lymph node metastatic tumor consisting of high-grade MBC with a predominant metaplastic squamous cell carcinoma component (MSC) that progressed from LGASC and three cases of independent de novo MSC.
RESULTS
Unlike de novo MSC, LGASC and its associated MSC showed no TP53 mutation and tended to contain fewer structural variants than de novo MSC. Both LGASC and its associated MSC harbored the common GNAS c.C2530T:p.Arg844Cys mutation, which was more frequently detected in the cancer cell fraction of MSC. MSC associated with LGASC showed additional pathogenic deletions of multiple tumor-suppressor genes, such as KMT2D and BTG1. Copy number analysis revealed potential 18q loss of heterozygosity in both LGASC and associated MSC. The frequency of SMAD4::DCC fusion due to deletions increased with progression to MSC; however, chimeric proteins were not detected. SMAD4 protein expression was already decreased at the LGASC stage due to unknown mechanisms.
CONCLUSION
Not only LGASC but also its associated high-grade MBC may be genetically different from de novo high-grade MBC. Progression from LGASC to high-grade MBC may involve the concentration of driver mutations caused by clonal selection and inactivation of tumor-suppressor genes.
Topics: Humans; Female; Carcinoma, Adenosquamous; Breast Neoplasms; Breast; Carcinoma
PubMed: 37650999
DOI: 10.1007/s10549-023-07078-9 -
Diagnostics (Basel, Switzerland) Jun 2022Microglandular adenosis is a non-lobulocentric haphazard proliferation of small round glands composed of a single layer of flat to cuboidal epithelial cells. The...
Microglandular adenosis is a non-lobulocentric haphazard proliferation of small round glands composed of a single layer of flat to cuboidal epithelial cells. The glandular structures lack a myoepithelial layer; however, they are surrounded by a basement membrane. Its clinical course is benign, when it is not associated with invasive carcinoma. In around 30% of cases, there is a gradual transition to atypical microglandular adenosis, carcinoma in situ, and invasive breast carcinoma of several different histologic subtypes, including an invasive carcinoma of no special type, metaplastic matrix-producing carcinoma, secretory carcinoma, metaplastic carcinoma with squamous differentiation, acinic cell carcinoma, spindle cell carcinoma, and adenoid cystic carcinoma. Recent molecular studies suggest that microglandular adenosis is a non-obligate precursor of triple-negative breast carcinomas. In this manuscript, we present a unique case of microglandular adenosis associated with metaplastic matrix-producing carcinoma and HER-2 neu oncoprotein positive pleomorphic lobular carcinoma in situ with apocrine differentiation in a 79-year-old patient.
PubMed: 35741268
DOI: 10.3390/diagnostics12061458 -
Archives of Pathology & Laboratory... Sep 2011Choriocarcinomatous differentiation has been described in tumors arising from many organs including lung, rectum, colon, stomach, bladder, and rarely breast. Mammary... (Review)
Review
Choriocarcinomatous differentiation has been described in tumors arising from many organs including lung, rectum, colon, stomach, bladder, and rarely breast. Mammary carcinoma with choriocarcinomatous features is a rare variant of breast metaplastic carcinoma characterized by malignant cells morphologically resembling choriocarcinoma cells in which reactivity with human placental lactogen and human chorionic gonadotropin can be demonstrated by immunohistochemistry. The characteristic syncytiotrophoblast-like giant cells seen in these neoplasms are more commonly associated with moderately to poorly differentiated carcinomas with or without a clear-cut mesenchymal component. Most of the reported cases have behaved very aggressively. The reason for this poor prognosis remains unclear. Because of the small number of cases, special treatment protocols have not been developed and these patients are treated surgically and with the standard chemotherapeutic agents available for other types of carcinoma of the breast. Pathologically, these tumors must be distinguished from metastatic choriocarcinoma to the breast.
Topics: Breast Neoplasms; Choriocarcinoma; Chorionic Gonadotropin; Combined Modality Therapy; Female; Humans; Prognosis
PubMed: 21877993
DOI: 10.5858/2010-0334-RSR1.1 -
Digestive Diseases and Sciences Aug 2018Esophageal adenocarcinoma (EAC) develops from Barrett's esophagus (BE), a condition where the normal squamous epithelia is replaced by specialized intestinal metaplasia... (Review)
Review
Esophageal adenocarcinoma (EAC) develops from Barrett's esophagus (BE), a condition where the normal squamous epithelia is replaced by specialized intestinal metaplasia in response to chronic gastroesophageal acid reflux. In a minority of individuals, BE can progress to low- and high-grade dysplasia and eventually to intra-mucosal and then invasive carcinoma. BE provides researchers with a unique model to characterize the process by which a carcinoma arises from its precursor lesion. Molecular studies of BE have demonstrated that it is not simply a metaplastic tissue, but rather it harbors frequent alterations that are also present in dysplastic BE and in EAC. Both BE and EAC are characterized by loss of heterozygosity, aneuploidy, specific genetic mutations, and clonal diversity. Epigenetic abnormalities, primary alterations in DNA methylation, are also frequently seen in BE and EAC. Candidate gene and array-based approaches have demonstrated that numerous tumor suppressor genes exhibit aberrant promoter methylation, and some of these altered genes are associated with the neoplastic progression of BE. It has also been shown that the BE and EAC epigenomes are characterized by hypomethylation of intragenic and non-coding regions Recent studies have also provided new insight into the evolutionary forces underlying the molecular alterations seen in BE and EAC and into the molecular pathogenesis of EAC.
Topics: Adenocarcinoma; Barrett Esophagus; Biomarkers, Tumor; Epigenesis, Genetic; Esophageal Neoplasms; Esophagus; Evolution, Molecular; Humans; Metaplasia
PubMed: 29766388
DOI: 10.1007/s10620-018-5090-8 -
Breast Cancer Research : BCR Jan 2023Metaplastic breast carcinoma (MpBC) typically consists of carcinoma of no special type (NST) with various metaplastic components. Although previous transcriptomic and...
BACKGROUND
Metaplastic breast carcinoma (MpBC) typically consists of carcinoma of no special type (NST) with various metaplastic components. Although previous transcriptomic and proteomic studies have reported subtype-related heterogeneity, the intracase transcriptomic alterations between metaplastic components and paired NST components, which are critical for understanding the pathogenesis underlying the metaplastic processes, remain unclear.
METHODS
Fifty-nine NST components and paired metaplastic components (spindle carcinomatous [SPS], matrix-producing, rhabdoid [RHA], and squamous carcinomatous [SQC] components) were microdissected from specimens obtained from 27 patients with MpBC for gene expression profiling using the NanoString Breast Cancer 360 Panel on a NanoString nCounter FLEX platform. BC360-defined signatures were scored using nSolver software.
RESULTS
Hierarchical clustering and principal component analysis revealed a heterogeneous gene expression profile (GEP) corresponding to the NST components, but the GEP of metaplastic components exhibited subtype dependence. Compared with the paired NST components, the SPS components demonstrated the upregulation of genes related to stem cells and epithelial-mesenchymal transition and displayed enrichment in claudin-low and macrophage signatures. Despite certain overlaps in the enriched functions and signatures between the RHA and SPS components, the specific differentially expressed genes differed. We observed the RHA-specific upregulation of genes associated with vascular endothelial growth factor signaling. The chondroid matrix-producing components demonstrated the upregulation of hypoxia-related genes and the downregulation of the immune-related MHC2 signature and the TIGIT gene. In the SQC components, TGF-β and genes associated with cell adhesion were upregulated. The differentially expressed genes among metaplastic components in the 22 MpBC cases with one or predominantly one metaplastic component clustered paired NST samples into clusters with correlation with their associated metaplastic types. These genes could be used to separate the 31 metaplastic components according to respective metaplastic types with an accuracy of 74.2%, suggesting that intrinsic signatures of NST may determine paired metaplastic type. Finally, the EMT activity and stem cell traits in the NST components were correlated with specimens displaying lymph node metastasis.
CONCLUSIONS
We presented the distinct transcriptomic alterations underlying metaplasia into specific metaplastic components in MpBCs, which contributes to the understanding of the pathogenesis underlying morphologically distinct metaplasia in MpBCs.
Topics: Humans; Female; Breast Neoplasms; Transcriptome; Proteomics; Vascular Endothelial Growth Factor A; Gene Expression Profiling; Carcinoma, Squamous Cell; Metaplasia
PubMed: 36707876
DOI: 10.1186/s13058-023-01608-5 -
Acta Radiologica Open Apr 2021Low-grade adenosquamous carcinoma is a less frequent variant of metaplastic breast carcinoma, incidentally detected during screening and has an age distribution similar... (Review)
Review
Low-grade adenosquamous carcinoma is a less frequent variant of metaplastic breast carcinoma, incidentally detected during screening and has an age distribution similar to other breast carcinomas. It shares characteristics with both benign and malignant carcinomas: its mammographic and sonographic features are therefore nonspecific. Breast conserving surgery with adjuvant radiation therapy is currently the preferred therapeutic approach. The aim of this review is to describe the imaging and clinical features of low-grade adenosquamous carcinoma for appropriate identification and diagnosis. The associated pitfalls, histopathologic and epidemiologic factors, natural course, and management of low-grade adenosquamous carcinoma are also discussed.
PubMed: 34017612
DOI: 10.1177/20584601211013501 -
Advances in Clinical and Experimental... Apr 2018Metaplastic carcinoma of the breast (MpBC) is defined as a group of heterogeneous malignant neoplasms that contain glandular and non-glandular components with mixed...
BACKGROUND
Metaplastic carcinoma of the breast (MpBC) is defined as a group of heterogeneous malignant neoplasms that contain glandular and non-glandular components with mixed epithelial and mesenchymal differentiations.
OBJECTIVES
The aim of this study was to research the clinical and pathological characteristics of MpBC determining its rank among all breast cancers.
MATERIAL AND METHODS
Metaplastic carcinoma of the breast was found in 7 out of 1,164 patients who had been diagnosed with breast cancer within the period of 12 years in our hospital. Demographic and clinical characteristics of the patients were retrieved from the patient files, and their final status was verified by a phone call. Diagnoses of the patients were confirmed by examining hematohylen and eosin (H&E) preparations. They were stained immunohistochemically for estrogen receptor (ER), progesterone receptor (PR), C-erbB-2, CK5/6 (Sitokeratin5/6), and EGFR (epidermal growth factor receptor), and the subgroups were determined according to the WHO classification.
RESULTS
All patients were female with a median age of 61 years (41-87 years). Three of them were diagnosed with stage IIB, 2 with IIIB and 1 with IV. Four patients had squamous type of metaplastic cell differentiation, 1 spindle, 1 adenosquamous, and 1 osteosarcomatous. In 6 out of 7 patients, ER, PR and C-erbB-2 expressions were negative immunohistochemically. In the case of squamous metaplasia, estrogen receptor was 10% and progesterone receptor was 5% positive. CK5/6 was positive in 5 cases. Epidermal growth factor was positive in all cases.
CONCLUSIONS
Metaplastic carcinoma of the breast is relatively rare and, in our series, its incidence was 0.6%. According to its immunohistochemical characteristics, MpBC can be interpreted as a subgroup of triplenegative breast cancers (TNBC). Five of the presented patients resembled the subgroup of TNBC with a basaloid phenotype. The chemotherapy regimens suggested in the treatment of MpBC are platin in the epithelial subgroup and high-dose anthracycline in the mesenchymal subgroup. There is a need of new studies that evaluate different choices of treatment as MpBC has a bad prognosis and an aggressive nature.
Topics: Biomarkers, Tumor; Breast Neoplasms; Carcinoma; ErbB Receptors; Female; Humans; Immunohistochemistry; Metaplasia; Middle Aged; Prognosis; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Triple Negative Breast Neoplasms
PubMed: 29558027
DOI: 10.17219/acem/68293 -
Nature Communications Apr 2020Metaplastic breast carcinoma (MBC) is a highly aggressive form of triple-negative cancer (TNBC), defined by the presence of metaplastic components of spindle, squamous,...
Metaplastic breast carcinoma (MBC) is a highly aggressive form of triple-negative cancer (TNBC), defined by the presence of metaplastic components of spindle, squamous, or sarcomatoid histology. The protein profiles underpinning the pathological subtypes and metastatic behavior of MBC are unknown. Using multiplex quantitative tandem mass tag-based proteomics we quantify 5798 proteins in MBC, TNBC, and normal breast from 27 patients. Comparing MBC and TNBC protein profiles we show MBC-specific increases related to epithelial-to-mesenchymal transition and extracellular matrix, and reduced metabolic pathways. MBC subtypes exhibit distinct upregulated profiles, including translation and ribosomal events in spindle, inflammation- and apical junction-related proteins in squamous, and extracellular matrix proteins in sarcomatoid subtypes. Comparison of the proteomes of human spindle MBC with mouse spindle (CCN6 knockout) MBC tumors reveals a shared spindle-specific signature of 17 upregulated proteins involved in translation and 19 downregulated proteins with roles in cell metabolism. These data identify potential subtype specific MBC biomarkers and therapeutic targets.
Topics: Adult; Aged; Aged, 80 and over; Animals; Biomarkers, Tumor; Carcinoma, Ductal, Breast; Carcinoma, Squamous Cell; Epithelial-Mesenchymal Transition; Extracellular Matrix; Female; Humans; Inflammation; Metabolic Networks and Pathways; Metaplasia; Mice; Middle Aged; Mutation; Protein Biosynthesis; Proteome; Proteomics; Sarcoma; Spindle Apparatus; Triple Negative Breast Neoplasms
PubMed: 32265444
DOI: 10.1038/s41467-020-15283-z -
Scientific Reports Dec 2020The management of metaplastic breast carcinoma (MBC) has largely paralleled the paradigms used for invasive ductal carcinoma (IDC) in the current National Comprehensive... (Clinical Trial)
Clinical Trial
The management of metaplastic breast carcinoma (MBC) has largely paralleled the paradigms used for invasive ductal carcinoma (IDC) in the current National Comprehensive Cancer Network guidelines of breast cancer. However, patients with IDC and MBC have been shown to have a different prognosis, and there are significant differences in risk and failure patterns after treatment. The purpose of this study was to compare breast cancer specific survival (BCSS) and hazard function between IDC and MBC. We included patients from the Surveillance, Epidemiology, and End Results program with stage I-III IDC and MBC between 2000 and 2012. Statistical analyses were including chi-square analysis, life-table methods, multivariate Cox proportional hazards models, and propensity score matching (PSM). We identified 294,719 patients; 293,199 patients with IDC and 1520 patients with MBC. Multivariate analyses showed that the MBC subtype had significantly lower BCSS than the IDC subtype before and after PSM (p < 0.001). There were significant differences in the hazard curve between IDC and MBC. The hazard curve for breast cancer mortality in the IDC cohort peaked at 3 years (2%), and then changed to a slowly decreasing plateau after prolonged follow up. However, the hazard curve for breast cancer mortality in the MBC cohort peaked at 2 years (7%), then declined sharply between 3 and 6 years, and changed to a low death rate after a follow-up time exceeding 6 years. Subgroup analyses revealed that the hazard curves significantly differed between IDC and MBC after stratifying by tumor stage and hormone receptor status. Our study suggests that patients with MBC should receive more effective systemic agents and intensive follow-up because of their significantly augmented risk of death compared to IDC patients.
Topics: Aged; Breast Neoplasms; Carcinoma, Ductal, Breast; Disease-Free Survival; Female; Humans; Longitudinal Studies; Middle Aged; Neoplasm Invasiveness; Risk Factors; Survival Rate
PubMed: 33328559
DOI: 10.1038/s41598-020-79166-5 -
Revista Da Associacao Medica Brasileira... Oct 2016Metaplastic tumors are rare and represent a heterogeneous group of neoplasms showing dominant areas of non-glandular differentiation. Etiology and pathogenesis of this... (Review)
Review
Metaplastic tumors are rare and represent a heterogeneous group of neoplasms showing dominant areas of non-glandular differentiation. Etiology and pathogenesis of this type of lesion in the breast is uncertain. The most common sources of metastatic squamous cell carcinoma of the breast are lung, esophagus, cervix, and urinary bladder. Squamous cell carcinomas may present clinically with inflammation and average size greater than breast adenocarcinoma. As for imaging studies, mammography shows no typical findings and ultrasound can show a complicated cyst or an inflammatory process, among the differential diagnoses. Therefore, knowing this pathological entity, its clinical course and imaging findings is important to safely treat such a rare and aggressive disease. We herein report a case of metaplastic carcinoma, squamous subtype, diagnosed by core needle biopsy.
Topics: Biopsy, Large-Core Needle; Breast Neoplasms; Carcinoma, Squamous Cell; Female; Humans; Mammography; Metaplasia; Middle Aged; Ultrasonography, Doppler, Color
PubMed: 27925039
DOI: 10.1590/1806-9282.62.07.618