Chapter 29 - A Primer on Immunostains Flashcards
CD31
Endothelial cells and megakaryocytes (cytoplasmic and membranous), also macrophages
To identify endothelial differentiation or angiosarcoma (most specific endothelial marker)
CD34
soft tissue
Endothelial cells, fibroblasts, and hematopoietic blasts (cytoplasmic and membranous)
To identify vascular sarcomas, Kaposi’s sarcoma, GIST, SFT, DFSP, epithelioid sarcoma, and some other soft tissue tumors. Synovial sarcoma is negative.
FVIII
blood vessels
Endothelial cells, megakaryocytes, platelets (cytoplasmic)
To identify endothelial differentiation
EMA
Epithelial, perineural, meningothelial cells (cytoplasmic or membranous)
To identify meningioma, perineuroma, chordoma, mesothelioma, sebaceous carcinoma and some sarcomas (synovial, epithelioid) and plasma cell neoplasms.
Name some entities that are EMA positive, keratin negative.
Meningioma, perineuroma, plasma cell myelomas.
GFAP
Glial cells (cytoplasmic)
To identify astrocytoma, GBM, ependymoma, and myoepithelial tumros of salivary gland. OGD and neuroblastoma are negative.
NSE (Neuron-specific enolase)
Neuroectodermal and neuroendocrine cells (cytoplasmic)
To identify neural differentiation but not very specific. Sensitive for neuroblastoma.
S-100
Glial cells, shwann cells, dendritic and langerhans cells, melanocytes, other mesenchymal cells (cytoplasmic and nuclear)
To identify schwannoma, gliomas, granular cell tumor, chordoma, ependymoma, MPNST, and melanocytic lesions. Breast can be positive.
Synaptophysin
Neuroendocrine cells (cytoplasmic)
To identify carcinoid, paraganglioma, pheochromocytoma, small cell, medullary carcinomas, neuroblastoma, islet cell tumors…
E-cadherin
Normal ductal and lobular cells (membranous)
Loss of staining identifies lobular carcinoma.
ER/PR
Estrogen receptor (nuclear) and progesterone receptor (nuclear)
For breast cancer prognosis (response to tamoxifen) and to identify metastatic breast cancer and some gynecologic tumors.
GCDFP
Apocrine metaplasia of breast and apocrine sweat glands (cytoplasmic)
To identify breast carcinoma and sweat/salivary gland carcinoma.
Her2Neu
Growth factor receptor, weakly expressed on normal epithelium (membranous and cytoplasmic)
To evaluate breast carcinomas (poor prognosis, response to trastuzumab)
Ki67
breast
Any proliferating cell (nuclear)
To gauge mitotic activity for prognosis
Alpha-actin
breast
Smooth muscle: myoepithelial cells, blood vessels, myofibroblasts (cytoplasmic)
To delineate myoepithelial layer and rule out invasive cancer
p63
breast
Tumor suppressor gene (nuclear)
Stains myoepithelial cells but not endothelial and fibroblasts (cleaner than actin/SMMHC). Also stains metaplastic carcinoma.
CK903
breast
Myoepithelial cells (cytoplasmic and membranous) and usual ductal hyperplasia
To differentiate usual ductal hyperplasia from DCIS. Also stains metaplastic carcinoma.
AE1/AE3
Wide panel of keratins, except 8+18 (cytoplasmic).
To identify carcinomas in general in conjunction with Cam5.2
Cam5.2
Low and intermediate-weight keratins 8, 18, and 19 (cytoplasmic)
To identify carcinomas in general in conjunction with AE1/AE3. Also identifies hepatocellular carcinoma, some adrenal cortical tumors, and some other carcinomas.
CK5/6
Two specific high-molecular-weight keratins (cytoplasmic)
To differentiate squamous cell carcinoma or mesothelioma from adenocarcinoma (negative).
CK7
A specific low-molecular-weight cytokeratin (cytoplasmic)
Positive in above-the-diaphragm carcinomas. Used in conjunction with CK20.
CK20
A specific low-molecular-weight cytokeratin (cytoplasmic)
Positive in below-the-diaphragm carcinomas and Merkel cell carcinoma. Used in conjunction with CK7.
What carcinomas are CK7+/CK20+?
Urothelial carcinoma
Pancreatic carcinoma
Ovarian mucinous carcinoma
What carcinomas are CK7+/CK20-?
Breast carcinoma NSCLC Ovarian serous carcinoma Endometrial carcinoma Epithelial mesothelioma Thymoma
What carcinomas are CK7-/CK20+?
Colorectal carcinoma
Merkel cell carcinoma
What carcinomas are CK7-/CK20-?
Hepatocellular carcinoma CCRCC Prostate carcinoma Neuroendocrine small cell carcinoma Squamou cell carcinoma
AFP
germ cell and testis
Fetal tissues (cytoplasmic)
To identify yolk sac tumor and HCC
c-KIT
Germ cells, mast cells, interstitial cells of Cajal (cytoplasmic or membranous)
To identify seminoma, mature teratoma, and GIST
b-hCG
Syncytiotrophoblasts (cytoplasmic)
To identify choriocarcinoma and germ cell tumors, some adenocarcinomas
HPL
Trophoblasts (cytoplasmic)
To identify germ cell tumors, moles, and choriocarcinoma.
Ki-1 (CD30)
Activate lymphocytes
To identify embryonal carcinoma, Hodgkin’s lymphoma, and ALCL
PLAP
Placenta (cytoplasmic)
To identify germ cell tumors, ITGCN. Does not stain spermatocytic seminoma.
CA-125
(no normal tissue stains)
To identify nonmucinous ovarian carcinomas
Inhibin
Granulosa cells, Sertoli cells, others (cytoplasmic)
To identify sex cord stromal tumors (Granulosa, Sertoli, Leydig) and moles, choriocarcinomas, fibrothecomas, and adrenal cortical tumors
Melcam (CD146)
Intermediate trophoblasts
To identify PSTT, choriocarcinoma
Mesothelin
Mesothelial cells (membranous)
To identify serous ovarian carcinoma, mesothelioma, and pancreatic carcinoma (targetable for immunotherapy?)
p16
Cells infected by HPV (nuclear)
To identify HSIL & HPV lesions of cervix and to differentiate endocervical (positive) and endometrial (negative) adenocarcinoma
p53
Tumor suppressor gene variant that should be absent in normal cells (nuclear)
To identify EIC and serous carcinoma of endometrium
ALK
Fusion protein only expressed by lymphomatous cells
Stains a subset of ALCL and DLBCL. HL is negative.
BCL-2
Inhibits apoptosis, normally turns off in germinal center (cytoplasmic & membranous)
To differentiate follicular lymphoma from reactive follicles. Also stains mantle cell lymphoma. Burkitt’s is negative.
BCL-6
Germinal center cells (cytoplasmic)
To identify lymphomas of follicular origin (FCC, Burkitt’s lymphoma)
CD1a
Thymocytes and Langerhans cells (membranous)
To identify Langerhans cell proliferations, T-LBL
CDs 3, 4, 5, 7, 8
T-cells
To identify T-cell lymphomas/leukemias; CD4 also dimly positive in monocyte/histiocyte lesions
CD10
heme
Precursor B + T cells, granulocytes (membranous)
To identify FCC, ALL, LBL, Burkitt’s lymphoma, and CML; MALTomas are negative.
CD20
B cells (cytoplasmic & membranous)
Used as a pan-B-cell marker; stains B-cell lymphomas, but plasmacytomas are negative.
CD15 (LeuM1)
heme
Granulocytes and macrophages (membranous and dot-like perinuclear)
To identify RS cells (HD), some large T-cell lymphomas and mycosis fungoides
CD23
B-cells, IgE receptor (membranous)
To identify SLL/CLL; mantle cell lymphomas are negative
CD30
Activated B + T cells, immunoblasts, other nonheme cells (cytoplasmic, membranous)
To identify RS cells, ALCL, large B- and T-cell lymphomas
CD34
heme
Hematolymphoid blasts, fibroblasts, and endothelial cells (cytoplasmic and membranous)
To identify blasts in the marrow in acute leukemias; also many soft tissue tumors
CD45 (CLA/LCA)
Lymphocytes, granulocytes, and histiocytes, but not plasma cells (cytoplasmic, membranous)
To identify poorly differentiated neoplasms as of hematopoietic origin
CD56
NK cells (membranous)
To idenitify natural killer/T-cell lymphomas
CD68
Histiocytes/macrophages/monocytes, granulocytes, others (cytoplasmic, membranous)
To identify histiocytic origin; also stains soft tissue tumors
CD79a
B-cells and plasma cells (membranous)
To identify B-cell neoplasms negative for other B-cell markers…
CD138
Plasma cells (membranous), epithelial cells
To identify plasma cell neoplasms
Cyclin D1
Nuclear stain in mantle cell lymphoma
To identify mantle cell lymphoma
EBV EBER
EBV RNA in infected B-cells (nuclear)
To identify EBV-related tumors, including nasopharyngeal carcinoma, post-transplant/AIDS lymphomas, and mononucleosis.
FVIII (vWF)
heme
Megakaryocytes, platelets, and endothelial cells (cytoplasmic)
To identify megakaryocytic leukemias
Hemoglobin
Hemoglobin in erythroid cells (cytoplasmic)
To identify erythroid leukemias
Kappa/Lambda
Light chains of immunoglobulins in plasma cells and B-cells (cytoplasmic)
Restricted staining indicates monoclonal B/plasma cell population
Ki67
heme
Any proliferating cell (nuclear)
To gauge mitotic activity and identify Burkitt’s lymphoma (100% positivity)
MPO
Enzyme granules in myeloid-lineage cells (cytoplasmic)
To identify AML and myeloid sarcoma (chloroma)
TdT
Immature lymphocytes (nuclear)
To identify LBL and ALL
RCC (gp200/RTA)
Proximal renal tubules (cytoplasmic)
To identify renal cell carcinoma
TFE3
Transcription factor (nuclear)
To identify Xp11-translocation RCC and alveolar soft part sarcoma
TFE3B
Transcription factor (nuclear)
To identify t(6;11) renal cell carcinoma
Thrombomodulin
Endothelial (cytoplasmic) and mesothelial (membranous) cells
To identify TCC, mesothelioma, some vascular tumors
WT-1
Tumor suppressor gene in developing nephrons; nephrogenic rests and adult glomerular podocytes (nuclear)
To identify Wilm’s tumor; also mesothelioma, desmoplastic small round cell tumor
A1-antitrypsin
Histiocytes and reticulum cells (cytoplasmic)
To highlight globules of A1-antitrypsin disease; not specific to a tumor
b-Catenin
APC-binding protein present in most cells (nuclear is significant and abnormal)
To identify colon cancer, abdominal fibromatosis, and solid pseudopapillary tumor of pancreas
CD10
Liver canaliculi, brush border of small bowel, other tissues
A canlicular pattern in HCC
pCEA
Fetal tissues and adenocarcinomas (cytoplasmic)
A canalicular pattern in HCC (not seen with mCEA); also stains lung, colon, pancreatic carcinoma
DPC-4 clone B8
Most normal tissues (cytoplasmic)
To identify pancreatic carcinoma (55% lose staining)
EGFR
Hepatocytes, perineurium in peripheral nerves, squamous epithelium
Prediction of response to anti-EGFR antibodies in advanced colon cancer
HepPar1 (OCH1E5)
Mitochondria in normal hepatocytes (granular cytoplasmic)
To identify HCC
BerEP4
Epithelial cells (membranous)
To differentiate mesothelioma from carcinoma
mCEA and pCEA
Fetal tissues and mucin-secreting glandular tissues (cytoplasmic)
To differentiate mesothelioma from adenocarcinoma
Calretinin
Various neural and epithelial cells (cytoplasmic and nuclear)
To differentiate epithelial mesothelioma (positive) from carcinoma (negative)
LeuM1 (CD15)
lungs
Hematopoietic cells and some carcinomas (membranous and cytoplasmic)
To differentiate mesothelioma (negative) from adenocarcinoma
TTF-1
Transcription factor in lung and thyroid (nuclear)
To differentiate nonsquamous carcinoma of lung origin from nonpulmonary, and to identify thyroid carcinomas.
WT-1
Tumor suppressor gene in mesothelium and developing nephrons, nephrogenic rests and adult podocytes (nuclear)
To differentiate epithelial mesothelioma from carcinomas, and to identify desmoplastic small round cell tumor and Wilms’ tumor
HMB45
Immature melanocytes (cytoplasmic)
To identify epithelioid melanoma, metastatic melanoma, angiomyolipoma, clear cell sarcoma, perivascular epithelioid cell tumors, and others
MART-1/Melan-A (N2-7C10 clone)
Melanocytes (cytoplasmic)
To identify melanoma (mainly epithelioid), more sensitive than HMB45. Recognizes same protein as Melan-A antibody
Melan-A (A103 clone)
Melanocytes (cytoplasmic)
To identify melanoma (mainly epithelioid), more sensitive than HMB45; also angiomyolipoma. Unlike MART-1, labels steroid cell tumors
MitF
Melanocytes (nuclear)
To identify melanoma and melanocytic tumors, also angiomyolipoma
S-100 protein
Melanocytes, glial cells, dendritic and Langerhans cells, other mesenchymal cells (nuclear and cytoplasmic)
To identify nevi and melanoma (most sensitive), cellular schwannoma, granular cell tumor, glial neoplasms. Not useful in lymph nodes.
Chromogranin
Neurosecretory granules (cytoplasmic and granular) in endocrine tissues and neurons
To differentiate pheochromocytoma from adrenal cortical carcinoma (negative), or to identify neuroendocrine tumors
Inhibin
Adrenal cortical cells (cytoplasmic)
To identify adrenal cortical tumors, stromal sex cord tumors, and fibrothecomas
Synaptophysin
Neuroendocrine cells (cytoplasmic), neuromuscular junction, Merkel cells
To identify neuroendocrine tumors
(various neuroendocrine hormones like gastrin, insulin)
(cells that produce the respective hormone)
To identify products of neuroendocrine tumors, such as islet cell tumors and others
CK903
prostate
High-molecular-weight keratin (cytoplasmic and membranous) in basal cells
To identify prostatic basal cells (lost in cancer) and urothelial carcinomas (positive)
p63
prostate
Prostatic gland basal cells (nuclear)
To identify basal cells (lost in cancer)
PSA
Prostatic epithelium (cytoplasmic), salivary gland
To identify metastatic or ambiguous prostate cancer. Seminal vesicle is negative.
PSAP (PAP)
Prostatic epithelium (cytoplasmic)
To identify metastatic or ambiguous prostate cancer and uroCA; also stains rectal carcinoids
Racemase (p504s)
Prostatic carcinoma
To confirm prostate carcinoma; also stains nephrogenic adenoma of bladder
Alpha-actin
soft tissue
Smooth muscle actin (cytoplasmic)
To identify smooth muscle differentiation, leiomyoma/leiomyosarcoma. Rhabdomyosarcoma is usually negative.
Actin (HHF-35)
Smooth, skeletal, and cardiac muscle, myoepithelial cells (cytoplasmic)
To identify muscle differentiation
CD99 (O13)
A variety of mesenchymal cells (membranous)
To identify PNET/Ewing’s, lymphocytes in thymoma, plus other sarcomas and hematologic tumors. Neuroblastoma is negative.
Desmin
Intermediate filaments in smooth, striated, and cardiac muscle (cytoplasmic)
To identify muscle differentiation
FXIIIa and CD68
Fibrohistiocytic cells (cytoplasmic)
To identify fibrohistiocytic tumors, such as MFH and dermatofibroma (FXIIIa), giant cell tumor of tendon sheath
Myogenin
Regenerating, but not normal, skeletal muscle (cytoplasmic)
To identify rhabdomyosarcoma
Vimentin
Most mesenchymal cells (cytoplasmic), including fibroblasts, endothelium, smooth muscle
As an internal control for immunoreactivity and antigen preservation (the “pan-keratin” of soft tissue)
Calcitonin
C-cells of the thyroid (cytoplasm and extracellular)
To identify medullary carcinoma of thyroid
Thyroglobulin
Thyroid follicles (cytoplasmic)
To identify metastatic thyroid carcinoma