Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The molecular characterization of human mammary myoepithelial cells is incomplete, hindering our understanding of its importance in breast physiology and pathology. Because data on the precursors of this cell lineage remain scarce and often contradictory, basal epithelial cells of second trimester fetal breasts were studied by light microscopy (LM) and immunohistochemistry (IHC). Up to 20 wk of gestational age, the mammary rudiments only comprised roundish primary outgrowths, "primary buds," more likely to represent immature nipples than true mammary tissue. At 21 wk secondary outgrowths, "projections," extended from enlarged primary buds into well-vascularized layers of dense mesenchyme. Basal projection cells had a partial myoepithelial-like phenotype: they reacted with CD29, CD49f, CD104, keratin 14, vimentin, S100beta protein, and p63; furthermore, many became positive for keratin 17, alpha-smooth muscle actin, and CD10 (but not for keratin 19) between wk 21 and 25. The continuous basement membrane associated with the fetal mammary rudiments was strongly positive for collagens type IV and VII, and for laminin 5. Consistently strong and basally polarized staining for hemidesmosomal components suggested that although incompletely differentiated, most second trimester myoepithelial precursors might already mediate local epithelial-mesenchymal interactions, i.e., complex signaling pathways which are crucial for both orderly growth during development and maintenance of homeostasis during adult life. Because they are likely implicated in the phenomenon of menstrual cycle-related growth spurts in the adult resting breast, the strategically positioned cells of the myoepithelial lineage might constitute critical protagonists in defective epithelial-mesenchymal signaling associated with cancer progression.
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PMID:Basal cells of second trimester fetal breasts: immunohistochemical study of myoepithelial precursors. 1470 33

The identification of an outer layer of myoepithelial cells is a valuable clue in the differential diagnosis of breast lesions. Myoepithelial cells can usually be appreciated with standard hematoxylin-eosin stains, however in pathology practice one encounters difficult cases, particularly in core biopsy specimens. There are several reported markers for the immunohistochemical detection of myoepithelial cells. Smooth muscle specific proteins, such as smooth muscle actin, smooth muscle myosin heavy chain, calponin and h-caldesmone are utilized to highlight myoepithelium. Smooth muscle actin is the most commonly used and has been established as a specific and sensitive marker. However, sometimes the staining can not be interpreted, since actin stains stromal fibroblasts and vascular smooth muscle cells as well. S100 protein and specific cytokeratins (keratins 5,7,14 and 17) also stain myoepithelial cells, but the staining is not specific and is not optimally sensitive. Maspin and CD10 are relatively new and promising markers. The nuclear protein p63 has attracted much attention in recent reports. p63-positive myoepithelial cells have been shown to surround benign epithelial lesions and form a consistent, although discontinuous, rim around epithelial cells in carcinomas in situ. No staining has been noted in infiltrative carcinomas. p63-immunostaining is nuclear and so it is easily appreciated, even in cytologic preparations. It is also highly specific since neither stromal fibroblasts nor vascular smooth muscle cells are stained. In conclusion, it appears that p63 is a sensitive and specific myoepithelial marker and may be included in immunohistochemical panels aiming at identifying myoepithelial cells in problematic breast lesions.
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PMID:The usefulness of p63 as a marker of breast myoepithelial cells. 1475 23

In the literature, sufficient attention has not been paid to the precise subcellular localization of immunohistochemical signals, the knowledge of which is essential for proper interpretation of immunostains and distinction of genuine staining from biotin-associated or other nonspecific stainings. The subcellular localization of the signals can in fact be easily deduced from the known biologic or ultrastructural characteristics of the antigens. Extracellular antigens obviously are located in the extracellular compartment. Cellular antigens fall into 3 major groups: membranous, nuclear, and cytoplasmic. Membranous antigens include cell adhesion molecules (such as E-cadherin, N-CAM), cell surface/transmembrane receptors and proteins (such as tyrosine kinase receptors, most leukocyte antigens, CD10, CEA), and molecules linking surface molecules to cytoskeleton (such as beta-catenin, dystrophin). Nuclear antigens include cell cycle-associated proteins (such as cyclins, p16, Ki-67), nuclear enzymes (such as TdT), transcription factors (such as TTF-1, CDX-2, myogenin, PAX-5), tumor suppressor gene products (such as p53, p63, WT1, Rb), steroid hormone receptors (such as ER, PR), calcium-binding proteins (such as S-100 protein, calretinin), and some viral proteins (such as CMV, herpes). Cytoplasmic antigens can take up a granular pattern due to localization in organelles, granules, or secretory vesicles (such as chromogranin, hormones, lysozyme, HMB-45), fibrillary pattern attributable to the filamentous nature of the molecules (intermediate filaments and microfilaments), or diffuse or patchy pattern due to localization in the cytosol or large vesicles (such as myoglobin, albumin, thyroglobulin). Aberrant localization of the molecules, when present, can provide important insight into disease processes and aid in their diagnosis, such as loss of membranous E-cadherin expression in lobular breast carcinoma, aberrant nuclear localization of beta-catenin in colorectal adenocarcinoma, pattern of ALK staining in anaplastic large cell lymphoma correlating with the different types of chromosomal translocations, presence of additional cytoplasmic CD10 staining in the enterocytes indicative of microvillous inclusion disease, and "reversed" staining for EMA in micropapillary mammary carcinoma.
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PMID:Subcellular localization of immunohistochemical signals: knowledge of the ultrastructural or biologic features of the antigens helps predict the signal localization and proper interpretation of immunostains. 1530 32

We investigated 20 spindle cell (sarcomatoid) metaplastic carcinomas (MCs) without squamous differentiation. In addition, five high-grade phyllodes tumors were assessed for comparison. Our immunohistochemical antibody panel included pan-cytokeratin (CK), low molecular weight CK (CK8/18), four basal cell type CKs (34betaE12, CK5/6, CK14, and CK17), vimentin antibodies, as well as antibodies to established (SMA, CD10, p63, S-100, maspin, calponin, GFAP, SM-myosin), and novel (CD29, 14-3-3sigma) myoepithelial markers. Sixteen of the 20 tumors (80%) expressed at least two markers of the combination CD10/p63/SMA. S-100 detected 1 case negative for CD10/p63/SMA and 3 cases that only expressed one marker of this combination. While 18 MCs (90%) were positive for CD29, 14-3-3sigma (11 cases) and maspin (9 cases) were observed in 55% and 45%, respectively. Antibodies to pan-CK and the basal cell type CKs were strongly reactive in 12 tumors (60%), but in 6 cases (30%) positivity for these markers was weak and only focal; 2 MCs showed no positivity for CK. The stromal component of all phyllodes tumors was positive for vimentin, whereas all other investigated markers were absent except for focal p63 and CD10 expression in 1 case each. Our findings convincingly show a myoepithelial immunophenotype in sarcomatoid MCs, which is demonstrated by the presence of basal cell type CKs and the combination of the established myoepithelial markers CD10, p63, SMA, and S-100. We conclude that tumors with weak or even absent CK expression should only be diagnosed as primary sarcomas of the breast after exclusion of a myoepithelial immunophenotype. CD29 and 14-3-3sigma represent valuable novel myoepithelial markers in these diagnostically difficult cases.
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PMID:Metaplastic breast carcinomas: are they of myoepithelial differentiation?: immunohistochemical profile of the sarcomatoid subtype using novel myoepithelial markers. 1572 3

Microarray profiling of invasive breast carcinomas has identified five distinct subtypes of tumors (luminal A, luminal B, normal breast-like, HER2 overexpressing, and basal-like) that are associated with different clinical outcomes. The basal-like subtype is associated with poor clinical outcomes and is the subtype observed in BRCA1-related breast cancers. The aim of this study was to characterize the histologic and immunophenotypic properties of breast basal-like carcinomas that were first positively identified using DNA microarray analysis. Detailed histologic review was performed on 56 tumors with known microarray profiles (23 basal-like, 23 luminal, and 12 HER2+). Immunohistochemistry for estrogen receptor (ER), HER2, EGFR, smooth muscle actin (SMA), p63, CD10, cytokeratin 5/6, cytokeratin 8/18, and vimentin was performed on 18 basal-like, 16 luminal, and 12 HER2+ tumors. The basal-like tumors were grade 3 ductal/NOS (21/23) or metaplastic (2/23) carcinomas that frequently showed geographic necrosis (17/23), a pushing border of invasion (14/23), and a stromal lymphocytic response (13/23). Most basal-like tumors showed immunoreactivity for vimentin (17/18), luminal cytokeratin 8/18 (15/18), EGFR (13/18), and cytokeratin 5/6 (11/18), while positivity for the myoepithelial markers SMA (4/18), p63 (4/18) and CD10 (2/18) was infrequent. All basal-like tumors tested were ER- and HER2-. Morphologic features significantly associated with the basal-like subtype included markedly elevated mitotic count (P<0.0001), geographic tumor necrosis (P=0.0003), pushing margin of invasion (P=0.0001), and stromal lymphocytic response (P=0.01). The most consistent immunophenotype seen in the basal-like tumors was negativity for ER and HER2, and positivity for vimentin, EGFR, cytokeratin 8/18, and cytokeratin 5/6. The infrequent expression of myoepithelial markers in basal-like carcinomas does not support a direct myoepithelial cell derivation of these tumors. These findings should further assist in the identification of basal-like carcinomas in clinical specimens, facilitating treatment and epidemiologic studies of this tumor subtype.
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PMID:Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma. 1634 Nov 46

Morules develop in several neoplasms and have been considered as a type of squamous metaplasia despite the absence of keratinization and intercellular bridges. The objective of this study was to clarify the pathological significance of morules and to distinguish morules from squamous metaplasia in colonic neoplasms. Ten cases of morule-associated colonic neoplasms (4 adenocarcinomas, 1 adenoma with carcinoma in situ, and 5 adenomas), and 3 cases of squamous metaplasia in colonic adenocarcinoma were examined morphologically and immunohistochemically. Morules were well-defined structures composed of small, oval to short-spindled cells with bland nuclei, and frequently associated with intranuclear inclusions that were positive for biotin and biotin-binding enzymes (pyruvic acid carboxylase and propionyl CoA carboxylase). On immunohistochemical examination, morules characteristically showed nuclear overexpression of beta-catenin, cyclin D1 and p63, low Ki-67 labeling index (<1%), cytoplasmic overexpression of CD10, and no expression of cytokeratin 20. These molecules were useful for the differentiation of morules. Furthermore, p63 and 34betaE12 positivities in morules suggested that they have a basal/stem cell phenotype. Thus, morules were morphologically and qualitatively different from squamous metaplasia. We consider that morules in colonic neoplasms are cell clusters with a basal/stem cell phenotype, and have less proliferative and less invasive potential than other cancer cells.
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PMID:Immunohistochemical analysis of morules in colonic neoplasms: morules are morphologically and qualitatively different from squamous metaplasia. 1637 71

A case of adenoid basal epithelioma (ABE) of the uterine cervix in 21-year-old woman is reported. The patient's age appears to be lowest among cases of ABE reported to date. The tumor showed typical histologic features of ABE and was associated with CIN3. In addition, rare tumor cells had surface cilia-appearing structures suggesting tubal differentiation. Immunohistochemically, the tumor was reactive for p63, CD10, ER, PR, p16 and bcl-2, and negative for CEA. Thus, the immunophenotype also suggests possible partial tuboendometrioid differentiation in the glandular component of the lesion. It further indicates, along with finding of associated CIN, a role of oncogenic HPV in pathogenesis of ABE.
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PMID:Adenoid basal epithelioma of the uterine cervix in 21-year-old patient. Report of a case with histologic and immunohistochemical study. 1638 92

The immunohistochemical detection of myoepithelial cells in benign sclerosing lesions of the breast is useful in distinguishing them from tubular carcinoma. So far, this detection has been carried out using antibodies against cytoskeletal proteins, such as alpha-smooth muscle actin (1A4) and calponin. However, the specificity of these markers has been questioned since they may be expressed in stromal myofibroblasts and vascular smooth muscle. Recently, two novel myoepithelial markers have been described: the nuclear protein p63, a member of the p53 family, and the surface antigen CD10, also known as common acute lymphoblastic leukemia antigen (CALLA). The authors assessed the use of p63 and CD10 in the differential diagnosis between benign sclerosing lesions, such as sclerosing adenosis and radial scar, and tubular carcinoma, in comparison to the traditional myoepithelial markers 1A4 and calponin. p63, CD10, 1A4, and calponin were expressed in myoepithelial cells of all benign lesions and were consistently negative in all cases of tubular carcinoma. In contrast to cytoskeletal proteins, p63 and CD10 were mostly confined to myoepithelial cells and thus were more specific than the traditional counterparts. However, 1A4 was more intensely expressed and more reproducible than the novel markers. In conclusion, p63 and CD10 may be used as a complement to 1A4 in distinguishing benign sclerosing lesions from tubular carcinoma of the breast.
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PMID:p63 and CD10: reliable markers in discriminating benign sclerosing lesions from tubular carcinoma of the breast? 1654 Jul 34

A novel human mammary epithelial cell line, HME348, was established from benign breast tissue from a 44-year-old germ-line BRCA2 mutation carrier with a history of stage 1 breast cancer. Mutation analysis showed that the patient had a known 6872del4 BRCA2 heterozygous mutation. The human mammary epithelial cells passaged in culture exhibited cellular replicative aging as evidenced by telomere shortening, lack of telomerase activity, and senescence. Ectopic expression of telomerase (hTERT) reconstituted telomerase activity in these cells and led to the immortalization of the cells. When grown on glass, the majority of immortalized HME348 cells expressed ESA and p63 with a small population also expressing EMA. In three-dimensional Matrigel culture, HME348 cells formed complex branching acini structures that expressed luminal (EMA, CK18) and myoepithelial (p63, CALLA, CK14) markers. Three clones derived from this culture were also p63(+)/ESA(+)/EMA(+/-) on glass but formed similar acinar structures with both luminal and myoepithelial cell differentiation in Matrigel confirming the mammary progenitor nature of these cells. Additionally, the experimentally immortalized HME348 cells formed acini in cleared mammary fat pads in vivo. As this is the first report establishing and characterizing a benign human mammary epithelial cell line derived from a BRCA2 patient without the use of viral oncogenes, these cells may be useful for the study of BRCA2 function in breast morphogenesis and carcinogenesis.
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PMID:Telomerase immortalization of human mammary epithelial cells derived from a BRCA2 mutation carrier. 1654 10

Immunohistochemistry is widely used for pathological diagnosis of breast lesions. Other than hormone receptors and HER2/neu analysis for primary breast carcinomas, several markers may be useful for differential diagnoses, although in limited situations. To decide the malignant potential of intraductal proliferative lesions, analysis for the staining pattern of cytokeratins may be a good reference. Most ductal carcinoma in situ cases are diffusely positive for luminal cell markers (CK8, CK18, CK19), but negative for basal cell markers (CK5/6 and CK14). However, usual ductal hyperplasia may show the mosaic staining patterns for any of these markers, which may indicate a heterogeneous cell population in benign lesions. Myoepithelial markers (alpha-SMA, myosin, calponin, p63, CD10) are almost consistently positive for benign papillomas but they do not completely distinguish intraductal papillary carcinomas. Preservation of myoepithelial layer is the diagnostic key when looking at benign sclerosing lesions, including carcinoma with pseudoinvasive structures. E-cadherin is mostly positive for ductal carcinomas but negative for lobular carcinomas. Some of the lobular carcinomas are positive for 34betaE12, but they are consistently negative for CK5/6. Comparison with histopathological findings of hematoxylin and eosin is essential to make proper diagnosis in the individual case.
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PMID:New trends of immunohistochemistry for making differential diagnosis of breast lesions. 1657 8


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