Stains A-E
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(routine stains, immunostains and molecular markers)
Last revised 12 December 2007
Copyright © 2002-2007 PathologyOutlines.com, Inc.
See also CD Marker chapters
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Note: stains/proteins are in alphabetical order, with numbers before letters, and ignoring dashes and spaces
Next update: desmin
Primary references, immunohistochemistry basics, common panels, biopsy interpretation, enzyme cytochemistry
B:
Cytokeratins: general, CK1, CK2, CK3, CK4, CK5, CK6, CK7, CK8, CK9, CK10, CK11, CK12, CK13, CK14, CK15, CK16, CK17, CK18, CK19, CK20, CK21, CK22, CK23, CK24, 34betaE12, 35betaH11, AE1, AE3, AE1-AE3, CAM5.2, KL-1, MNF116
D:
E:
Go to Stains F-Z and cell cycle
American Journal of Surgical Pathology (AJSP), January 2001 to April 2002, January to October 2005
Archives of Pathology and Lab Medicine (Archives), January to October 2005
Human Pathology (Hum Path), June to September 2005
Modern Pathology (Mod Path), February 2002, February to March 2005, August to October 2005
Rosai, J: Ackerman’s Surgical Pathology (9th Ed); Mosby, 2004
University of Pittsburgh Medical Center Case Reports
Cytokeratins: updated Apr07
Please refer to these primary references for more detailed discussions and photographs
Antibodies are often useful beyond their recommended expiration dates
Focus on what type of cells are staining (tumor cells, endothelial cells, stromal cells)
Note the number (percent) of cells staining, the intensity of staining and the pattern of staining (cytoplasmic, membranous, nuclear, dot like)
Pattern of immunoreactivity must follow the anatomic distribution of the antigen before it is called positive / immunoreactive
Repeating or performing additional tests may be important when reviewing slides of patients with prior diagnosis of cancer (AJSP 2002;26:1222)
Sources of error in interpretation are ectopic antigen expression, cross reactions, less specificity than thought
Note: diagnosis should be based on H&E morphology, with confirmation by immunohistochemistry or molecular testing; it is dangerous to use immunohistochemistry alone to make the diagnosis
Steps in immunohistochemistry:
1. pretreatment, often with microwaving of tissue in citrate buffer to unmask antigens hidden by formalin cross-links or other fixative
2. other agents for pretreatment (antigen retrieval) are pepsin, proteases, trypsin
3. apply primary antibody (monoclonal antibodies usually are more specific); antibody binds to antigens of interest
4. wash off excess primary antibody
5. add biotinylated anti-IgG antibody (secondary antibody), which binds to the primary antibody present
6. add avidin-biotin-peroxidase complex, which binds to secondary antibody
7. add 3, 3’ diaminobenzidine (DAB) as a chromagen (color changing reagent), with hematoxylin counterstaining
Other enzyme complexes besides avidin-biotin are horseradish peroxidase, alkaline phosphatase with naphthol phosphate and glucose oxidase with nitroblue tetrazolium
Other chromagens besides DAB are AEC (water soluble, sensitive to light)
Most important steps are selection of appropriate antibodies, correct interpretation, technical quality and integration of results into final diagnosis (AJSP 2002;26:873)
Common panels of immunohistochemistry stains
Epithelial markers: low molecular weight keratin (CAM 5.2), AE1-AE3 cytokeratin cocktail, CK7, CK20, CEA, EMA
Melanocytic markers: S100 (also a mesenchymal marker), HMB45, MelanA/Mart1
Mesenchymal markers: vimentin, Factor XIIIa, Factor VIII, CD31, CD34, HHF35, smooth muscle actin, desmin
Lymphoid markers: CD3, CD20, CD15, CD30, various others
Histiocytic markers: CD68, lysozyme, CD1a (Langerhans cells)
Neuroendocrine markers: neuron specific enolase, chromogranin, synaptophysin
Cell proliferation/apoptosis markers: Ki-67, bcl2
Recommended to interpret immunohistochemical stains in small needle core biopsy specimens based on the area with the greatest immunoreactivity (AJCP 2007;127:273)
Detects enzymatic activity in cytoplasm
Enzyme product unites with coupler, which produces localized color at site of enzyme activity
Fresh smears are preferred, especially for myeloperoxidase; if not possible, store unstained slides away from light
3 beta hydroxysteroid dehydrogenase
Critical enzyme in biosynthesis of all steroid hormones
Positive staining (normal): testicular Leydig cells
Negative staining: normal seminiferous tubules
7-amino-actinomycin D (7 AAD)
DNA-binding, fluorescent dye is excited by 488 nm laser line commonly used in flow cytometry
Intact cells exclude 7 AAD; dead cells allow 7 AAD entry, which binds to DNA
Used in flow cytometry to reduce non-specific staining by eliminating 7 AAD positive cells (dead cells) from further analysis
14-3-3 sigma protein
Member of highly conserved family of acidic proteins
Phosphoserine binding protein that mediates G2/M arrest; also other cellular signaling pathways
May be a tumor suppressor, induced by DNA damage and p53
Cytoplasmic staining
Positive staining (normal): urothelium, prostate and breast periductal and periglandular cells, uterus (strong in squamous epithelium, weak in endometrial and endocervical glands)
Positive staining-tumors: bladder urothelial carcinoma (98%), cervical squamous cell carcinoma (67%), endometrial adenocarcinoma (57%), prostatic adenocarcinoma (55%), ovarian carcinoma (33%), testicular tumors (27%), breast carcinoma (23%), renal carcinoma (12%)
Negative staining: germinal cells of testis and ovary, kidney (sporadic expression in tubules)
References: Mod Path 2005;18:340
45M1
Recognizes peptide core of M1 gastric mucin antigen
Positive staining (normal): normal gastric epithelium
Positive staining (disease): intestinal metaplasia in Barrett’s esophagus, AJSP 2001;25:87
Negative staining: mature small intestinal goblet cells
A beta 42
42 amino acid protein; variant of APP
May be prone to forming plaques in Alzheimer’s
Deposited early in plaques; may be a seed for other plaques
abl
also called c-abl; gene at 9q34.1, named after abelson murine leukemia virus
Functions as a tyrosine kinase / signal transducer and a negative regulator of apoptosis
Overexpression causes resistance to apoptosis induction by Fas, ceramide or chemotherapy
Overexpressed in chronic myelogenous leukemia
Acid fast bacilli (AFB)
Acid fast refers to organisms whose cell wall has a high lipid content of mycolic acids and long chain fatty acids, which causes them to bind and retain the complex basic dye carbolfuchsin even after strong decolorization with acid-alcohol.
Mycobacteria, cryptosporidium, isospora, and the hooklets of cysticerci are acid fast
AFB stains use either Ziehl-Neelsen, Kinyoun’s or Fit methods
Auramine-rhodamine stain for mycobacteria requires a fluorescence microscope, but is the most sensitive stain for mycobacteria
Acid phosphatase
Enzyme histochemistry technique
Positive staining: osteoclasts
Enzyme cytochemistry: T-ALL (focal paranuclear), AML (variable)
Acridine Orange
Used for staining low numbers of bacteria; examine under ultraviolet light
Mammals have at least 6 actin isoforms - two smooth muscle (alpha smooth muscle and gamma smooth muscle), two sarcomeric (alpha cardiac and alpha skeletal) and two nonmuscle (beta cytoplasmic and gamma cytoplasmic)
Functions: muscle cells - contraction; all cells - forms part of cytoskeleton, associated with motility
References: Wikipedia
Actin, alpha cardiac type
There are two types of alpha sarcomeric/striated actin: cardiac type and skeletal muscle type; both are expressed in cardiac and skeletal muscle, but the proportions vary at different developmental periods (J Biol Chem 1994;269:12212) or with disease (Rapid Commun Mass Spectrom 2003;17:1467)
Mutations in cardiac type may cause dilated or hypertrophic cardiomyopathy (J Mol Cell Cardiol 2000;32:1687), atrial septal defects (Hum Mol Genet 2007 Oct 18 [Epub ahead of print])
Positive staining (normal): myocardium (adult and fetal), skeletal muscle (fetal), skeletal muscle (adult-muscle spindle myocytes), vascular smooth muscle (occasional)
Positive staining (disease): skeletal muscle (regenerating skeletal muscle cells [Differentiation 1996;60:245], Duchenne muscular dystrophy, degenerative atrophy), rhabdomyosacoma, Wilm’s tumor-rhabdomyomatous cells, occasional smooth muscle tumors
Negative staining (normal): skeletal muscle (adult, but muscle spindle myocytes are positive)
References: Virchows Arch 2006;449:175
Actin, alpha skeletal type
There are two types of alpha sarcomeric/striated actin: cardiac type and skeletal muscle type; both are expressed in cardiac and skeletal muscle, but the proportions vary at different developmental periods (J Biol Chem 1994;269:12212) or with disease (Rapid Commun Mass Spectrom 2003;17:1467)
Absence causes nemaline myopathy (Ann Neurol 2007;61:175)
Positive staining: rhabdomyosarcoma (but not commonly used, AJSP 1985;9:467)
Actin, alpha smooth muscle type
Also called smooth muscle actin, SMA; clone 1A4 or sm-1
Discovered in 1986 (J Cell Biol 1986;103:2787)
Antibodies to alpha smooth muscle actin do not detect the other actin isoforms
Reduced expression in brain blood vessels in Alzheimer patients (J Neuropathol Exp Neurol 2004;63:735)
No apparent deficiency in intestinal pseudoobstruction (J Clin Pathol 2004;57:1168)
Uses:
(a) identify smooth muscle cells and myofibroblasts in normal, reactive (Am J Respir Cell Mol Biol 1999;20:582) or neoplastic tissue (Am J Dermatopathol 2006;28:105)
(b) identify myoepithelial cells in normal, neoplastic or diseased breast, salivary glands or sweat glands; may be helpful to rule out invasion; may be particularly important in cytology specimens (Anticancer Res 2003;23:4175)
(c) identify pericytes, which are associated with mature microvessels and better prognosis in colorectal carcinoma (Oncology 2005;69:159)
(d) help distinguish pleuropulmonary desmoid tumors (SMA+) from solitary fibrous tumor (SMA-, Archives 2006;130:1503)
Note: in breast papillary lesions, p63 is a more sensitive and specific marker because smooth muscle actin also stains stromal cells (J Clin Pathol 2007;60:315)
Interpretation: membranous or cytoplasmic staining
Positive staining (normal): myoepithelial cells of breast (most but not all, Breast Cancer Res 2003;5:R151), salivary glands, sweat glands and tracheobronchial glands (J Histochem Cytochem 1988;36:659); myofibroblasts (except alveolar-J Histochem Cytochem 1992;40:1955 and some granulation tissue/scars-Lab Invest 1989;60:275, Int J Legal Med 1992;105:99), pericytes (J Histochem Cytochem 1989;37:315), smooth muscle, vascular smooth muscle; also chondrocytes (Folia Biol (Praha) 2006;52:167), choroidal non-vascular smooth muscle cells (J Anat 2005;207:381), decidual stromal cells (Hum Reprod 1999;14:1599), fibroblastic reticulum cells (J Cancer Res Clin Oncol 1981;101:149), glomus coccygeum (Archives 1999;123:905), hepatic stellate cells (Virchows Arch 1997;430:195), osteoblasts (J Orthop Res 2002;20:622)
Actin, alpha smooth muscle (continued)
Positive staining (disease): adenoid cystic carcinoma (Archives 1999;123:801), angiomyofibroblastoma (occasionally focal, Hum Path 1997;28:1046), angiomyolipoma, atypical teratoid/rhabdoid tumor (J Neurosurg 1996;85:56), collagenous spherulosis (Mod Path 2006;19:1351), endometrial stromal sarcoma (65%, Gynecol Oncol 2004;92:71), endometriosis-stroma (Pathol Int 2003;53:371), epithelial-myoepithelial carcinoma (AJSP 2007;31:44), epithelioid sarcoma-proximal type (33%, AJSP 1997;21:130), fibromatosis (56%, AJSP 2002;26:1296), fibroblastic reticulum cell tumor (AJSP 1998;22:1048), gastric carcinoma stromal cells (J Clin Pathol 2002;55:741), GIST (45%, AJSP 2002;26:1296), glomus tumor (Hum Path 1999;30:1259), granulosa cell tumors of ovary-adult (variable, Mod Path 1995;8:25), hemangiopericytoma (AJSP 2003;27:737), kidney-focal segmental glomerulosclerosis (Braz J Med Biol Res 2001;34:985), inflammatory myofibroblastic tumor (Ann Diagn Pathol 2001;5:335, AJSP 1992;16:896), leiomyoma, leiomyosarcoma, liposarcoma (focal in some cases, AJSP 2004;28:1257), melanoma-desmoplastic (Am J Dermatopathol 1999;21:537), mesothelioma-sarcomatoid (60%, Histopathology 2003;42:270), MFH (30%, J Clin Pathol 2003;56:666), myoepithelioma (57%, Hum Path 2004;35:14), myofibroblastoma (occasionally focal, Pathology 2005;37:144, AJSP 2001;25:1022), myofibroblastic sarcoma (Chin Med J (Engl) 2007;120:363), nodular fasciitis (Ann Diagn Pathol 2002;6:94), ossifying fibromyxoid tumor (some, J Laryngol Otol 1993;107:75), pancreatic stellate cells post-obstruction (J Surg Res 2003;114:6), plexiform fibrohistiocytic tumor (Histopathology 1991;19:503), pulmonary lymphangioleiomyomatosis (J Clin Pathol 1993;46:479), renal mixed epithelial and stromal tumor (Archives 2006;130:80), rhabdomyoma (focal/rare, Hum Path 1993;24:754, Hum Path 1993;24:608), rhabdomyosarcoma (botryoid type, Pediatr Dev Pathol 2005;8:427), spindle cell carcinoma (AJSP 2001;25:1009), synovial sarcoma (25%, Mod Path 2007;20:760)
Negative staining (normal): cardiac muscle (positive during development-J Cell Sci 2007;120:229), skeletal muscle (J Cell Biol 1985;100:807)
Negative staining (disease): carcinomas (usually), schwannoma, solitary fibrous tumor (Archives 2006;130:1503)
Actin, muscle specific
Also called HHF35, MSA
Recognizes all alpha actins (skeletal, smooth, cardiac) and gamma smooth muscle actin
Recognizes actin expressed in all cells with muscle differentiation (cardiac, smooth and skeletal muscle), myoepithelial cells, myofibroblasts, pericytes and myogenic tumors; specific, these are alpha muscle isoforms and gamma smooth muscle actin
Discovered in 1987 (Am J Pathol 1987;126:51)
Uses:
(a) identify skeletal muscle (Tumori 2007;93:198, J Cutan Pathol 2007;34:352) and smooth muscle cells (Eur Respir J 2001;17:316) in normal tissue or various disease entities
(b) classify tumors of smooth or skeletal muscle, pericytes, myofibroblasts or with myoepithelial cells
(c) differentiate leiomyosarcoma (MSA+, keratin-) from spindle cell carcinoma (MSA-, keratin+, Am J Otolaryngol 2005;26:201)
Positive staining (normal): cardiac muscle, decidua, myoepithelial cells, myofibroblasts, pericytes, skeletal muscle, smooth muscle, vascular smooth muscle,
Positive staining (disease): adenoid cystic carcinoma (J Oral Maxillofac Surg 2006;64:415), chondroblastomas (35%, Hum Path 1997;28:316), endometriosis (Hum Reprod 2000;15:767), fibromatosis (Acta Cytol 1991;35:403), glioblastoma multiforme (occasional), glomus tumor (Hum Path 1999;30:1259), hemangiopericytoma (Head Neck 2005;27:124, AJSP 2003;27:737), inflammatory myofibroblastic tumor (Mod Path 2001;14:784), leiomyoma (Int J Gynecol Pathol 1995;14:134), leiomyosarcoma (80-100%, J Pak Med Assoc 2005;55:138, APMIS 1997;105:793), MFH (30%, J Clin Pathol 2003;56:666), myoepithelioma, myofibroblastic sarcoma (Chin Med J (Engl) 2007;120:363), myofibroblastoma (variable), osteosarcoma (AJCP 2000;113:663), pleomorphic adenoma (Hum Path 1991;22:1206, rhabdomyosarcoma (MyoD1 and myogenin are more specific/sensitive, AJSP 2006;30:962), solitary fibrous tumor (variable staining, Mod Path 1997;10:443)
Negative staining (disease): angiomyofibroblastoma (Pathol Int 1995;45:487), mesothelioma-epithelioid (AJSP 2006;30:463)
References: AJCP 1991;96:32
Adhesion molecules
Overexpressed in chronic inflammatory diseases, including synovium in rheumatoid arthritis
AE1, AE3
See Cytokeratin
AF-4
Gene at 4q21
Translocations with MLL via t(4;11)(q21;q23 ) in acute leukemia
AF-9
Gene at 9p22
Translocations with MLL via t(9;11)(p22;q23 ) in acute leukemia
AIB1
Also called SRC3, TRAM1
Member of steroid receptor coactivator 1 family at 20q12
Involved in cell proliferation, migration and differentiation
References: Hum Path 2005;36:777 (colorectal carcinoma)
Albumin
In-situ hybridization may be specific for hepatocellular carcinoma or hepatoid areas of combined hepatocellular-cholangiocarcinoma (AJSP 2002;26:989)
Alcian blue
Detects acidic mucins
At pH 1.0, detects highly acidic mucins
Alcian blue/high iron diamine
Positive staining: Sulfomucins - brown, sialomucins - blue
Alk (see also NPM-ALK)
Anaplastic lymphoma kinase gene at 2p23; Also called CD246
Membrane spanning tyrosine kinase receptor, member of insulin receptor family
Ligand is growth factor pleiotrophin
3' end contains catalytic domain of tyrosine kinase
t(2;5) associated with T cell anaplastic lymphoma via fusion of ALK and nucleophosmin protein
Has important role in brain development
ALK+ primary anaplastic large cell lymphomas have favorable prognostic significance
ALK- cases of primary anaplastic large cell lymphoma are associated with trisomy 2 (Mod Path 2005;18:235)
Positive staining (normal): normal small intestine, T cells; weakly positive in brain, colon, prostate
Positive staining (disease): T or null cell anaplastic lymphomas (some), inflammatory myofibroblastic tumor (AJSP 2001;25:1364, AJSP 2001;25:761)
Negative staining: fibromatosis, GIST, nodular fasciitis, normal lymphoid tissue
Alkaline phosphatase
Membrane bound glycoproteins, with hepatic, osseous, renal and placental isoenzymes
See PLAP
Positive staining (normal): osteoblasts
Positive staining (disease): mononuclear stromal cells from giant cell tumor of bone and soft tissue (Hum Path 2005;36:945)
ALL1
Gene at 11q23 also called MLL (mixed lineage leukemia), HRX, Htrx (from Drosophila trithorax protein)
Affected by self-fusion translocation of t(11;11)(q23;q23)
Self fusion causes the gene to be dominant negative by fusing with other genes
Trisomy causes loss of function of the gene, leading to B cells with both lymphoid and myeloid phenotypes
Self fusion involves “Alu” sequences, which are conserved elements of repetitive DNA in non-protein coding region
There are 1 million copies of Alu sequences in human genome, each about 300 base pairs in length
Alu mediated recombination causes partial duplication of the ALL1 gene
ALL1 tumors: usually CD10 negative, CD19+, with lymphoid and myeloid markers
Bone marrow transplantation recommended in childhood ALL with t(4;11)(q23;q23) due to otherwise poor prognosis
90% of all cases with ALL abnormalities are t(4;11), t(9;11), t(11;19)
Accounts for 5-10% of acute leukemias, usually M4 or M5
Present in 60% of infants < 1 year with ALL
Abnormal expression in 10% of ALL, 6% of AML, 80% of secondary leukemia after topoisomerase II inhibitor treatment
Alpha
Part of t(6;11)(p21;q12); TFEB and Alpha; renal neoplasm of children and young adults (AJSP 2005;29:230)
Gene is at 11q12; lacks introns or splice signals; does not code for a functioning protein
Can detect using DNA PCR as an alternative to RT-PCR since Alpha lacks splice signals
Nuclear stain
Alpha-1-antichymotrypsin
Acute phase plasma protease inhibitor, mainly produced by liver
Homologous to alpha-1-antitrypsin
Positive staining: histiocytes, reticulum cells
Alpha-1-antitrypsin
Homologous to Alpha-1-antichymotrypsin
Positive staining: histiocytes, reticulum cells
Alpha feto-protein (AFP)
Major plasma protein of early fetus; present in fetal gut, liver, yolk sac
Present in blood of pregnant women (some)
Undetectable after birth
Uses: (a) Hepatocellular carcinoma: 17-62% sensitive; sensitive even for poorly differentiated tumors, (b) Yolk sac tumors: sensitive and specific
Positive staining (disease): hepatocellular carcinoma, yolk sac tumors, other germ cell tumors
References: AJSP 2002;26:978
Alpha-lactalbumin
Major protein of human milk
Specific to breast tissue (normal, malignant, fibrocystic) and hydradenoma papilliferum of vulva
Alpha-naphthyl acetate / alpha-naphthyl butyrate
see Non specific esterase
Alpha-naphthyl chloroacetate esterase
Note: staining is opposite of alpha-naphthyl acetate
Positive staining: granulocytes
Negative staining: monocytes and lymphocytes
AMACR
Alpha MethylAcyl Coenzyme A Racemase; also called P504S
Identified from prostate adenocarcinoma by cDNA library subtraction coupled with high throughput microarray screening of human prostatic tissue
Also expressed in colorectal adenocarcinoma and other malignancies, but not in normal appearing small and large intestinal mucosa
A mitochondrial and peroxisomal enzyme involved in beta-oxidation of dietary branched-chain fatty acids and fatty acid derivatives (including bile acid intermediates)
Sensitive (82-95%) and relatively specific for prostate carcinoma vs. benign prostate (AJSP 2001;25:1397, AJSP 2002;26:1588)
In prostate carcinoma, is strongly positive, usually diffuse, regardless of Gleason grade
Relatively specific - benign prostate is usually negative or only focal/weakly positive; however partial atrophy and crowded benign glands may be positive (AJSP 2005;29:874)
Most specific if circumferential luminal to subluminal and diffuse cytoplasmic staining
Uses: identify small foci of prostatic adenocarcinoma, in conjunction with 34 beta E12 or p63 (AJSP 2002;26:1169), may identify a subset of AAH with a premalignant potential (AJSP 2002;26:921)
Positive staining (disease): prostatic adenocarcinoma and high grade PIN; partial prostatic atrophy and crowded benign prostatic glands may be positive (AJSP 2005;29:874); also overexpressed in lymphomas and cervical, colorectal adenocarcinoma (69-83%, AJSP 2005;29:890), breast, gastric, liver, ovarian, renal cell carcinomas (AJSP 2002;26:926), urothelial carcinoma (30%), primary (65%) and secondary (from colorectum) bladder adenocarcinomas (Mod Path 2005;18:1217)
Negative staining: benign prostate (usually, see exceptions under positive staining), atypical adenomatous hyperplasia (usually, 10% are positive, AJSP 2002;26:921); small intestinal adenocarcinoma (usually, only 4-6% are positive, AJSP 2005;29:890)
AMF
Autocrine motility factor
Induces the directed and random migration of AMF producing tumor cells
Expression of its receptor correlates with stage and recurrence in bladder carcinoma
Expression of its receptor is associated with down regulation of E-cadherin
AMH
Anti-Mullerian Hormone
High serum levels associated with granulosa cell tumors of ovary and testis
Positive staining (normal): prepubertal Sertoli cells
Negative staining: pubertal Sertoli cells
AML1
Gene at 21q22 is DNA binding component of AML1/CBF beta transcription factor complex, most frequent target of translocations in AML via t(8;21) [AML1-ETO]; t(12;21); t(3;21) [AML1-EVI1]
Fusion products (below) suppress normal AML1 mediated transactivating activity
Normal AML1 required to establish fetal liver-derived definitive hematopoiesis (stem cells to definitive hematopoietic elements)
Androgen receptor
Interpretation: nuclear stain
Positive staining (normal): skin apocrine and sebaceous glands
Positive staining (disease): high grade DCIS, high grade invasive breast carcinoma, mammary and extramammary Paget’s disease (Mod Path 2005;18:1283)
AP-1
Activator protein 1, a transcription factor complex composed of proteins that bind to AP-1 DNA recognition elements, which induces expression of genes controlling cell growth and apoptosis
Includes 4 subfamilies Jun, Fos, Maf and ATF, which function as a complex of homodimers and heterodimers
AP-2
Family of 5 transcription factors, all homologous 50 kDa proteins: AP-2alpha, AP-2beta, AP-2gamma, AP-2delta and AP-2epsilon, encoded by separate genes
These transcription factors homo- or heterodimerize and transactivate their target genes by binding to GC-rich sequences in their promoter regions
AP-2alpha represent CK18+ breast glandular epithelial cells and AP-2gamma represent smooth muscle actin+ myoepithelial cells in non-neoplastic breast tissue and DCIS
have distinct spatial distribution in non-neoplastic breast epithelia
References: Mod Path 2005;18:431
APC
Adenomatous polyposis coli gene on 5q21, tumor suppressor gene, autosomal dominant
Important for familial adenomatous polyposis and Gardner syndromes
Binds to (a) microtubule bundles and promotes cell migration and adhesion, (b) beta-catenin (cytoskeletal protein) in a cellular adhesion complex including E-cadherin, part of Wnt signaling pathway
Beta-catenin is also bound to a T cell factor-lymphoid enhancer factor (Tcf-Lef), which activates other genes, stimulates cell proliferation and inhibits apoptosis
APC accelerates the proteasome-mediated degradation of beta-catenin, which reduces its role as a transactivating factor for the Tcf-Lef pathway
Mutations in APC produce elevated levels of Tcf4-beta-catenin, which stimulates a transcriptional response that initiates polyp formation and eventually malignant growth
APC is considered a gatekeeper gene since it directs activity downstream of different pathways
Colon: mutations play critical role in tumorigenesis (mutations in APC or beta-catenin present in 90% of colon cancers)
API2
Member of the IAP (inhibitor of apoptosis) gene family; essential for suppression of apoptosis
API2-MALT1
Fusion protein associated with MALT lymphoma (50%); rarely with diffuse large B cell lymphoma
Due to t(11;18)(q21;q21) - API2 and MALT1
May lead to increased inhibition of apoptosis, helping MALT lymphoma cells to survive
References: Mod Path 2003;16:1232 (colorectal lymphoma), Hum Path 2003;34:1212 (diffuse large B cell lymphoma)
Apolipoprotein D (apoD)
Member of lipocalin superfamily of proteins involved in transport of cholesterol, steroid hormones and other small hydrophobic molecules
Correlates with cell cycle inhibition in various situations including cellular senescence
High levels in fibrocystic breast disease and HDL, but produced by almost all tissues in body
Expression upregulated in nonneoplastic regenerating peripheral nerve compared to normal, then downregulated during transformation to MPNST (Hum Path 2005;36:987)
Argentaffin
Argentaffin cells/tissues contains a substance (such as catecholamines, indolamines) that reduces silver and other metallic salts to metallic silver, staining brown or black
Argentaffin stains are: Fontana-Masson, Schmorl's, Autofluorescence, diazonium salt
Argyrophilic
Argyrophilic cells/tissues contain a substance that reduces silver solution to metallic silver after exposure to an extraneous reducing agent, such as hydroquinone or formalin
Argyrophilic stains: Grimelius (with Bouin's fixative), Churukian-Schenk’s modification, Pascual's
ARP
Arginine Rich Protein, 3p21
Deleted or mutated in 50% of sporadic renal cell carcinomas
ARPP
a protein including an Ankyrin Repeat PEST motif and Proline-rich region
Homologous to cardiac ankyrin-repeat protein and diabetes-related ankyrin repeat protein
May act as molecular link between myofibrillar stretch-induced signaling pathway and muscle gene expression
Expressed exclusively in striated muscle (in normal human tissue), within I band of sarcomere
Positive staining (disease): rhabdomyosarcoma (89%), epithelioid sarcoma (60%, focal/weak or strong), Ewing’s sarcoma (20%, focal/weak), malignant fibrous histiocytoma (10%, focal/weak), synovial sarcoma (10%, focal/weak)
Interpretation: definitive cytoplasmic staining is required (nuclear staining is nonspecific)
References: Hum Path 2005;36:620
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