(1)
Department of Pathology, Sinai Hospital of Baltimore Pathology, Baltimore, MD, USA
Keywords
CytokeratinMelanomaCarcinomaSarcomaLymphomaMesotheliomaGerm cell tumorVascularNeuralMyoepithelialThe use of immunostains is a highly complex field in and of itself and one that is changing so rapidly that no printed text can really keep up. This chapter is meant as an introduction to the most commonly used stains so that you can at least follow the thread of conversation when the acronyms begin to fly. Stains are organized by the organ system in which they are most often used. A much more comprehensive reference is Rekhtman and Bishop’s Quick Reference Handbook for Surgical Pathologists.
Table 31.1.
Blood vessels (endothelium).
Antibody | Normal tissues stained | When it is used |
|---|---|---|
CD31 | Endothelial cells and megakaryocytes (cytoplasmic and membranous), also macrophages | To identify endothelial differentiation or angiosarcoma; most specific endothelial marker |
CD34 | Endothelial cells, fibroblasts, and hematopoietic blasts (cytoplasmic and membranous) | To identify vascular sarcomas, Kaposi sarcoma, solitary fibrous tumor, DFSP, epithelioid sarcoma, plus some other soft tissue tumors. Synovial sarcoma is negative |
D240 | Lymphatic endothelium (cytoplasmic) | To identify vascular differentiation or lymphatics; also marks mesothelium |
FVIII | Endothelial cells, megakaryocytes, platelets (cytoplasmic) | To identify endothelial differentiation, specific but not very sensitive |
Table 31.2.
Brain and meninges.
Antibody | Normal tissues stained | When it is used |
|---|---|---|
EMA | Epithelial, perineural, meningothelial cells (cytoplasmic or membranous) | To identify meningioma, perineuroma, chordoma. Germ cell tumors (excluding some teratomas) are negative |
GFAP | Glial cells (cytoplasmic) | To identify astrocytoma and ependymoma; also myoepithelial tumors of salivary gland |
IDH1 | None: antibody stains mutant IDH1 (cytoplasmic) | To subclassify glial tumors (IDH1 mutated) |
INI1 | All normal cells (nuclear) | To identify atypical teratoid/rhabdoid tumor (loss of staining) |
NSE (neuronal-specific enolase) | Neuroectodermal and neuroendocrine cells (cytoplasmic) | To identify neural differentiation but not very specific (not the same as nonspecific esterase, an enzyme assay for heme path). Sensitive for neuroblastoma |
S100 | Glial cells, Schwann cells, dendritic and Langerhans cells, melanocytes, and other mesenchymal cells (nuclear and cytoplasmic) | To identify cellular schwannoma, astrocytomas, granular cell tumor, chordoma, ependymoma, MPNST, and melanocytic lesions (all types) |
Synaptophysin | Neuroendocrine cells (cytoplasmic) | To identify neuroendocrine tumors, paraganglioma, pheochromocytomas, small cell carcinoma, neuroblastoma, and others. Differentiates neural differentiation (positive) from glial (negative) |
Table 31.3.
Breast.
Antibody | Normal tissues stained | When it is used |
|---|---|---|
CK903 (CK5/6 is similar) | Myoepithelial cells (cytoplasmic and membranous) and usual duct hyperplasia | To differentiate usual ductal hyperplasia (positive) from ductal carcinoma in situ (negative). Also stains metaplastic carcinoma |
E-cadherin | Normal ductal and lobular cells (membranous) | Loss of staining identifies lobular carcinoma (in situ and invasive); ductal lesions are positive |
ER and PR | Estrogen receptor (nuclear) and progesterone receptor (nuclear) | For breast cancer prognosis (predicts response to tamoxifen) and to identify metastatic breast cancer, some gynecologic tumors, and others |
GATA3 | Breast epithelium (nuclear) | To identify breast differentiation in carcinoma; sensitive but not specific |
GCDFP | Apocrine metaplasia of the breast and apocrine sweat glands (cytoplasmic) | To identify breast differentiation in carcinoma, also sweat and salivary gland carcinoma |
Her2 | Growth factor receptor that is only weakly expressed in normal epithelial cells (membranous) | To evaluate breast carcinomas (overexpression is a poor prognostic sign but can be treated with Herceptin) |
Mammaglobin | Normal breast tissue (cytoplasmic) | To identify breast differentiation in carcinoma, also sweat and salivary gland carcinoma |
Stains that identify myoepithelial cells to rule out invasive carcinoma | ||
Calponin | Myoepithelial cells (cytoplasmic) | To delineate myoepithelial layer |
p63 | Tumor suppressor gene (nuclear) | Stains myoepithelial cells but not endothelium and fibroblasts. Also stains metaplastic carcinoma |
Smooth muscle myosin heavy chain (SMMHC) | Myoepithelial cells, blood vessels, myofibroblasts (cytoplasmic) | To delineate myoepithelial layer |
Smooth muscle actin (SMA) | Smooth muscle: myoepithelial cells, blood vessels, myofibroblasts (cytoplasmic) | To delineate myoepithelial layer; also stains myofibroblasts |
Table 31.4.
Cytokeratins.
Antibody | Normal tissues stained | When it is used |
|---|---|---|
AE1–AE3 (pankeratin) | Wide panel of keratins stains most epithelial cells (cytoplasmic), except cytokeratins 8 and 18 | To identify carcinomas in general; used in conjunction with cam 5.2 to screen for carcinoma |
EMA | Epithelial, perineural, meningothelial cells (cytoplasmic or membranous) | To identify meningioma, many carcinomas, plus some sarcomas (synovial sarcoma, epithelioid sarcoma), and plasma cell neoplasms. Germ cell tumors (excluding some teratomas) are negative |
Entities that are EMA-positive, keratin-negative: meningioma, perineuroma, plasma cell myeloma | ||
High-molecular-weight keratins | ||
CK5/6 | High-molecular-weight keratins, mainly in squamous and urothelial epithelia (cytoplasmic) | To differentiate squamous cell carcinoma (positive) or mesothelioma (positive) from adenocarcinoma (negative) |
CK903 (34ßE12) | High-molecular-weight keratins, mainly in squamous and urothelial epithelia (cytoplasmic and membranous) | To identify prostatic basal cells (loss of staining indicates carcinoma) and urothelial carcinoma (positive); also metaplastic breast carcinoma |
Low-molecular-weight keratins | ||
CK7 | A specific low-molecular-weight cytokeratin (cytoplasmic, membranous) | CK7 and CK20 are used in combination to narrow the differential of carcinoma of unknown origin. CK7 is generally positive in above-the-diaphragm carcinomas (see below on CK7 and CK20) |
CK20 | A specific low-molecular-weight cytokeratin (cytoplasmic, membranous) | Generally positive in below-the-diaphragm carcinomas and in Merkel cell carcinoma (see below on CK7 and CK20) |
cam 5.2 | Low- and intermediate-molecular-weight keratins 8, 18, and 19, in nonsquamous epithelia (cytoplasmic) | Used in conjunction with AE1/AE3 to screen for carcinoma. Also to identify hepatocellular carcinoma, some adrenal cortical tumors, and some carcinomas that are negative for other keratins (undifferentiated carcinoma) |
7/20 matrix | CK20 + | CK20 − |
CK7 + | Urothelial carcinoma | Breast carcinoma |
Pancreatic carcinoma | Lung carcinoma, non-small cell | |
Ovarian mucinous carcinoma | Ovarian serous carcinoma | |
Endometrial carcinoma | ||
Epithelial mesothelioma | ||
Thymoma | ||
CK7 − | Colorectal carcinoma | Hepatocellular carcinoma |
Merkel cell carcinoma | Renal cell carcinoma, clear cell type | |
Prostate carcinoma | ||
Neuroendocrine small cell carcinoma | ||
Squamous cell carcinoma | ||
Table 31.5.
Germ cell and testis.
Antibody | Normal tissues stained | When it is used |
|---|---|---|
β-hCG | Human chorionic gonadotropin β-chain (cytoplasmic) in syncytiotrophoblasts | To identify choriocarcinoma and germ cell tumors, some adenocarcinoma |
CD30 | Activated lymphocytes (cytoplasmic) | To identify embryonal carcinoma, Hodgkin lymphoma, and ALCL |
c-kit (CD117) | Germ cells, mast cells, interstitial cells of Cajal (cytoplasmic or membranous) | To identify seminoma (membranous) and mature teratoma, plus GIST in the stomach |
OCT3/4 | Developing brain and stem cells (nuclear) | To identify seminoma, embryonal carcinoma, and GCNIS |
PLAP | Placenta (cytoplasmic) | To identify germ cell tumors, GCNIS |
SALL4 | Fetal tissues, germ cells (nuclear) | To identify germ cell tumors (sensitive but not specific) |
SOX2 | Stem cells (nuclear) | To identify embryonal carcinoma; also stains squamous carcinomas |
Table 31.6.
Gynecologic.
Antibody | Normal tissues stained | When it is used |
|---|---|---|
Actin, desmin | Smooth muscle cells, myometrium (cytoplasmic) | To identify leiomyomas or leiomyosarcomas |
β-hCG | Syncytiotrophoblasts (cytoplasmic) | To identify choriocarcinoma and germ cell tumors |
CD10 | Endometrial stroma (cytoplasmic) | To identify endometrial stroma and stromal sarcoma |
ER, PR | Ovarian and endometrial tissues (nuclear) | To differentiate between some carcinomas and to identify treatment responsiveness |
Inhibin | Granulosa cells, Sertoli cells, and others (cytoplasmic) | To identify sex cord stromal tumors (granulosa, Sertoli, and Leydig cells) and hydatidiform moles, choriocarcinomas, fibrothecomas, and adrenal cortical tumors |
Napsin A | Pneumocytes, lung (cytoplasmic) | To identify clear cell carcinoma of the ovary, as well as lung carcinomas |
PAX8 | Renal and Mullerian tissues (nuclear) | To identify nonmucinous tumors of GYN origin, also stains renal and thyroid tumors |
p16 | Cells infected by HPV (nuclear), also benign tubal metaplasia | To identify HSIL and HPV lesions of the cervix and to differentiate between endocervical (positive) and endometrial (negative) adenocarcinoma; serous carcinoma also positive |
p53 | Tumor suppressor gene variant that should be absent in normal cells (nuclear) | To identify serous carcinoma of endometrium or the ovary, to identify STIC |
p57 | Expressed in trophoblastic cells (nuclear) | To confirm complete hydatidiform mole (negative); only expressed in maternally derived chromosomes
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