Immunohistochemistry Testing

Immunohistochemistry Testing

AFP: has been immunohistochemically demonstrated in yolk sac carcinomas of gonadal and extragonadal site, in hepatic malignancies and a few other neoplasms.

ALK-1: labels normal human ALK protein and the NPM-ALK chimeric protein, and it is a useful tool for the identification of the subgroup of anaplastic large-cell lymphomas (ALCL) that are ALK positive.

Arginase-1:  clone SP156 a rabbit monoclonal antibody used as a marker for hepatocellular carcinomas.

B72.3: recognizes TAG-72, a tumor-associated oncofetal antigen expressed by a wide variety of human adenocarcinomas: invasive ductal breast carcinomas, and colon, pancreatic, gastric, esophageal, lung, ovarian and endometrial adenocarcinomas. It is also expressed on normal secretory endometrium, but not on other normal tissues.

BCL-2: labels cells expressing BCL2 Oncoprotein and is a useful tool for the identification of lymphoproliferative diseases, and especially for the distinction between reactive lymphoid hyperplasia and follicular lymphoma.

BCL-6: stains cells in Follicular Lymphoma, Diffuse large B-cell lymphomas, Burkitt’s Lymphoma and the majority of Reed-Sternberg cells in nodular lymphocyte predominant Hodgkin’s Disease.

Calcitonin: identifies C-cell hyperplasia and medullary thyroid carcinomas.

Caldesmon: was designed for specific localization of both vascular and visceral smooth muscle.  In conjunction with calponin and Smooth Muscle Actin, Caldesmon could be used to distinguish benign and in-situ lesions from invasive carcinomas.

Calponin: could be used to distinguish benign and in-situ lesions from invasive carcinomas.  Markers for the myoepithelial cells stain positive most of the peripheral cells in benign breast lesions and carcinoma in situ, but fail to stain virtually any neoplastic cells in invasive carcinomas. The antibody may also be used to characterize the differentiation process of mammary myoepithelial cells in developing mammary gland, investigate the nature of myoepithelial cells, and to study the development of smooth muscle cells.

Calretinin: is useful in differentiating mesotheliomas from adenocarcinomas.

Cam5.2: is useful in the diagnosis of many tumors including undifferentiated carcinomas, adenocarcinomas, thymomas, spindle cell carcinomas, Merkel cell carcinomas, chordomas, mesotheliomas, neuroendocrine carcinomas, and certain sarcomas such as synovial and epithelial sarcomas.

CD1a: has been used to differentiate various cutaneous lymphomas (T-cell) from B-cell lymphomas and pseudolymphomas and is useful in the differential diagnosis of Langerhan’s cell histiocytosis and the classification of thymomas and malignancies of T-cell precursors.

CD3: is a pan T-cell marker for detecting normal and neoplastic T-cells.

CD4: is a marker of cutaneous T cell lymphoma, including mycosis fungoides, and HTLV-1 associated adult T cell leukemias and lymphomas.

CD5: is recommended for the identification of mantle cell lymphomas. It may be of particular use in the detection of T cell acute lymphocytic leukemias and some B cell chronic lymphocytic leukemias as well as B and T cell lymphomas.

CD7: is expressed by the majority of peripheral blood T cells, NK cells, and all thymocytes.  Widely used in the identification of immature and precursor T cell malignancies, such as angioblastic and lymphoblastic lymphomas

CD8:  is a T-cell marker for the detection of cytotoxic/suppressor cells of blood lymphocytes. CD8 is also detected on NK cells, most thymocytes, a subpopulation of null cells and bone marrow cells. This antibody, along with other markers can be used to distinguish between reactive and neoplastic T-cells.

CD10: is expressed on cells of lymphoblastic, Burkitt’s and follicular germinal center lymphomas, and on cells from patients with chronic myelocytic leukemia (CML).  It is also expressed in various non-lymphoid cells and tissues, such as breast myoepithelial cells, bile canaliculi, fibroblasts, with especially high expression on the brush border of kidney and gut epithelial cells.

CD15: may be used to aid in the identification of cells of granulocytic lineage and/or Reed Sternberg differentiation. The antigen is expressed in hematopoietic and non-hematopoietic neoplasms.  Mature leukocytes, monocytes and granulocytes show positive staining. It is useful in the diagnosis of Hodgkin lymphoma with positive membrane and or Golgi zone staining in Reed-Sternberg cells. CD15 may also be expressed in some carcinomas.

CD20: is a marker of the B-cell lineage and is very useful in the identification of neoplasms of B-cell derivation.

CD21: is a marker of follicular dendritic cells and is useful in evaluating the underlying architecture of lymphoid tissue

CD30: is a marker for the identification of anaplastic large-cell lymphoma (ALCL) and as a secondary marker for Hodgkin lymphoma.

CD31: is expressed on endothelial cells, and is a useful marker for the identification of benign and malignant vascular disorders, including angiosarcomas. In addition, it is valuable for the labeling of vessels when determining angiogenesis in several types of tumors.

CD 34: is an antigen expressed in some progenitor cells including myeloid and lymphoid cell lines, acute leukemias, and endothelial cells. Tumor cells that show membrane positivity include vascular neoplasms, solitary fibrous tumor, DFSP, hematopoietic neoplasms and others.

CD43: is expressed in T-cell lymphomas and mantle cell lymphomas.

CD45: is a marker for normal or neoplastic tissue of lymphoid origin.

CD56:  is a marker for neuroendocrine tumors and small cell carcinoma of the lung.  It also is expressed in astrocytomas, neuroblastomas, and some mesodermally derived tumors (rhabdomyosarcoma).

CD68: is a marker for the identification of neoplasms of myeloid and macrophage / monocyte origin. It is used in the identification of myelomonocytic and histiocytic tumors.

CD79a: is a marker for the identification of B cell neoplasms of all maturation stages.

CD99: is a membrane glycoprotein expressed by human thymocytes, most T-ALL cells, some red blood cells, and the small cell round tumors of Ewing’s sarcoma and peripheral neuroectodermal tumors. It is also present on some bone marrow, lymph nodes, spleen, granulosa cells of the ovary, most b cells, CNS ependymal cells, Sertoli cells of the testis and a few endothelial cells.

CD138: is a useful marker for normal and neoplastic plasma cells and plasmacytoid lymphomas.  Various forms of Hodgkin lymphoma have also shown positive staining with this antibody.

CDX-2: is expressed by carcinomas of intestinal origin.  In addition, adenocarcinomas with intestinal differentiation from other sites, such as, stomach or pancreas, can be positive.

CEA: is an epithelial glycoprotein found in many carcinomas including adenocarcinomas of the lung, colon, breast, bladder, other GI sites, among other tumors.

Chromogranin: is a marker for neuroendocrine and neuronal tumors including carcinoids, islet cell tumors, neuroendocrine carcinomas, and endocrine cell hyperplasias and neoplasias.

Ckit (CD117): is particularly useful in differentiating gastrointestinal stromal tumors (GIST) from Kaposi’s sarcoma, tumors of smooth muscle origin, fibromatosis, and neural tumors of the GI tract. It is also useful in recognizing myeloblasts in bone marrow core and clot.

CMV: Positive staining occurs within the nucleus or cytoplasm of cells infected by CMV.

C-MYC:  The transcription factor and cell cycle regulator MYC (c-MYC) is a well-recognized oncoprotein in B cell lymphoma.  A small subset of diffuse large B-cell lymphomas (DLBCLs) has translocations involving the MYC locus and an additional group has a molecular signature resembling Burkitt lymphoma.  This a standardized immunohistochemical approach to assess MYC protein expression in formalin fixed, paraffin embedded tissue which readily identifies DLBCLs with higher nuclear MYC protein expression.

Cyclin D1: is overexpressed in mantle cell lymphoma and carcinomas of the breast, head & neck, colon, skin, and urinary bladder.

Cytokeratin 5:  is a marker for the Basal Cell Variant of Breast Cancer (triple negative tumors), mesotheliomas and squamous cell carcinomas.

Cytokeratin 5/6:  is a marker for squamous or mesothelial differentiation.

Cytokeratin 7:  can help distinguish between lung, breast, and urothelial carcinomas that typically stain positive and colon and prostate carcinomas that typically lack CK7 expression. It is a common marker of primary lung adenocarcinoma. 

Cytokeratin 20:  is expressed by carcinomas originating from gastric and intestinal epithelium, urothelium and Merkel cells.

Cytokeratin 34bE12 (K903): is expressed by squamous and ductal neoplasms.

D2-40: is expressed by lymphovascular structures.

Desmin: is an intermediate filament found in skeletal, cardiac and smooth muscle.  It is expressed in neoplasms showing smooth or skeletal muscle differentiation.

E-Cadherin: is expressed by glandular epitheliums as well as adenocarcinomas of lung, G.I. tract and Ovary.  Loss of expression is characteristic of lobular neoplasms of the breast.

EMA: is a glycoprotein normally found on the membrane of epithelial cells. Expressed by carcinomas, Ki-1 Lymphoma, myeloma and plasmacytoma, and synovial and epithelioid sarcomas.

EPCAM-BerEP4:  is an antibody that labels most normal epithelial cells.  This epithelium-specific antigen is broadly distributed in epithelial cells, and displays a highly conserved expression in carcinomas.  The antibody is useful in the differential diagnosis between basal and squamous cell carcinomas of the skin.

ER: is expressed on normal and neoplastic epithelial cells. Positive staining may be observed in breast carcinoma most often, but immunoreactivity may also be seen in lung carcinomas, thyroid carcinomas, and endometrial and ovarian carcinomas.  It is most often used to determine presence or absence of receptor in breast carcinoma to guide hormonal therapy.

Factor XIIIA:  is a monoclonal antibody to the A-subunit of human coagulation Factor XIIIa.  Factor XIIIa is a dermal dendrocyte marker and shows variable reaction with these types of tumors.  It can be used for histiocytic phenotyping and has been reported to mark capillary hemangiomas and tumors of the central nervous system.  Factor XIIIa has also been used with CD34 to differentiate between dermatofibroma and dermatofibrosarcoma protuberans.  

Fascin:  is helpful in distinguishing between Hodgkin lymphoma and non-Hodgkin lymphoma.

GATA-3: clone L50-823 a mouse monoclonal antibody primarily seen in breast carcinoma and urothelial carcinoma.  It can be used in a panel of antibodies for diagnosis of unknown primary carcinoma when carcinomas of the breast or bladder are possible.

GCDFP-15: this marker may be used to aid in the identification of breast carcinomas with apocrine features.

GFAP: is expressed by glial neoplasms including astrocytomas and ependymomas.

Glypican-3: is a useful tumor marker for the diagnosis of hepatocellular carcinoma (HCC), hepatoblastoma, melanoma, testicular germ cell tumors, and Wilms’ tumors.

H. Pylori: demonstrates the presence of H. pylori. There is increasingly clear evidence of a role for H. pylori in the etiology of active chronic gastritis and in the development of peptic ulcer disease.

HCG: is expressed by cells of trophoblastic origin. HCG expression by non-trophoblastic tumors may indicate aggressive behavior since it has been observed that HCG may play a role in the host response to a given tumor. The presence of HCG in non-trophoblastic morphologically benign or atypical proliferating epithelium may indicate early malignant transformation.

Human Herpes Virus Type 8 (HHV-8):  is the likely etiologic agent of Kaposi’s sarcoma (KS).  HHV-8 DNA sequences have been found in Kaposi’s sarcoma lesions, primary effusion lymphoma, and multicentric Castleman’s disease via polymerase chain reaction and in situ hybridization.  Anti HHV-8 labels the latent nuclear antigen protein via immunohistochemistry.

Hepatic Specific Antigen (HSA): is a marker of both benign and malignant liver derived tissues including hepatoblastoma, hepatocellular carcinoma, and hepatic adenoma.

HSV: is used to determine if tissue is infected with the herpes simplex virus.

Inhibin Alpha: is expressed by Adrenal Cortex tumors. Sex Cord Stromal tumors of the ovary as well as trophoblastic tumors also express this marker.

Ki-67:  is expressed during G1, S, G2, and M phase of the cell cycle, while resting cells lack the antigen.  Constantly proliferating cells express the antigen during the entire cell cycle.  This allows direct monitoring of the proliferative fraction of normal and neoplastic tissue.

Muscle Actin: is a reliable marker for soft tissue tumors with muscle differentiation, i.e., leiomyomas, leiomyosarcomas, and rhabdomyosarcomas.

Melan-A: is expressed in the majority of human melanomas as well as in melanocytes.

Myeloperoxidase: is a marker that discriminates between lymphoid leukemias and myeloid leukemias.

MITF: is expressed in the majority of primary and metastatic epithelioid malignant melanomas as well as in normal melanocytes, benign nevi and dysplastic nevi.

MMR Panel (MLH1, MSH2, MSH6, PMS2):  The MSI panel antibodies are mismatch repair genes that can be deficient in a high proportion of patients with microsatellite instability (MSI-H).  This finding is associated with the autosomal dominant condition known as Hereditary Non-Polyposis Colon Cancer (HNPCC).

MUM1:  Multiple myeloma concogene-1 / IRF4 Interferon regulatory factor 4 is a 50kDa protein encoded by MUM1 gene, and a member of the interferon regulatory factor family of transcription factors.  MUM1/IRF4 is expressed in the nuclei and cytoplasm of plasma cells and a small percentage of germinal center (GC) B-cells located in the “light zone”.  This antibody stains MUM1 protein, which is expressed in a subset of B-cells in the light zone of the germinal center, plasma cells, activated T-cells, and a wide spectrum of related hematolymphoid neoplasms derived from these cells.  Therefore, this antibody is useful for the subclassification of lymphoid malignancies and an excellent marker for Hodgkin’s and Reed-Sternberg cells of classic Hodgkin’s disease in combination with anti-CD30

Myosin, Smooth Muscle:  Smooth muscle myosin, heavy chains (SMMS-1) is a cytoplasmic structural protein that is a major component of the contractile apparatus of the smooth muscle cells.  SMMS-1 is also a myoepithelium-associated protein.  Anti-SMMS-1 is a mouse monoclonal antibody to smooth muscle myosin, heavy chain that reacts with human visceral and vascular smooth muscle cells.  The antibody also reacts with human myoepithelial cells.  It is very helpful in distinguishing between benign sclerosing breast lesions and infiltrating carcinomas in difficult cases since it strongly stains the myoepithelial layer in the benign lesions while it is negative in the infiltrating carcinomas.

Napsin A:  is expressed in type II pneumocytes and in adenocarcinomas of the lung.  The high specificity expression of napsin A in adenocarcinomas of the lung is useful to distinguish primary lung adenocarcinomas from adenocarcinomas of other organs.

NKX3.1:  has a high specificity and sensitivity for prostate adenocarcinomas, metastatic prostate adenocarcinomas and can be used to help distinguish between prostate adenocarcinomas and urothelial carcinomas by nuclear staining.

OCT-4:  is a transcription factor that regulates and maintains pluripotency in embryonic stem and germ cells.  High sensitivity and specificity in seminoma/dysgerminoma, embryonal carcinoma, and the germ cell component of gonadoblastoma by nuclear immunostaining.

p16: is expressed in cervical cancer and has been associated with HPV positive and HPV negative cervical adenocarcinomas.

P40: is selectively expressed in lung SCC, offering an opportunity for improved specificity when compare to p63.

p53: is a protein that accumulates to a high level in malignant lesions, including breast, colon and stomach carcinomas, melanoma, urinary bladder transitional carcinoma, embryonal carcinoma of the testis, and soft tissue sarcomas.

p57: is a marker whose expression is governed by imprinting, and whose expression can be used in conjunction with DNA ploidy to differentiate a complete mole from a partial mole or hydropic abortus.

p63: is a marker for prostatic basal cells, breast myoepithelial cells, and squamous cell carcinomas.

P120 Catenin:  helps to differentiate between lobular and ductal breast carcinoma.  Lobular carcinoma of the breast shows intracytoplasmic accumulation of P120 Catenin while ductal carcinoma shows reduced membrane P120 carcinoma without cytoplasmic accumulation.  In gastric and colonic carcinoma, strong cytoplasmic P120 Catenin is associated with discohesive infiltrative morphology.  The high expression of P120 may indicate poor prognosis in lung adenocarcinomas, bladder cancer, and pancreatic cancer.

Pan Keratin: is expressed by normal and abnormal epithelial cells.

PAX-5: is a very specific nuclear marker for B-cells, including B-lymphoblastic neoplasms.  In approximately 97% of cases of classic Hodgkin’s lymphoma, Reed-Sternberg cells express Pax-5 with dim nuclear visualization. 

PAX-8: is a nuclear transcription factor expressed in neoplasms of thyroid, ovary, and kidney.

PLAP: is a marker for germ cell tumors and can discriminate between these and other neoplasms. Somatic neoplasms may also react with antibodies to PLAP.  PLAP positivity in conjunction with negative keratin favors seminoma over carcinoma.

PR: this antigen is expressed on normal and neoplastic epithelial cells. Positive staining may be observed in breast carcinoma most often, but immunoreactivity may also be seen in lung carcinomas, thyroid carcinomas, and endometrial and ovarian carcinomas.  It is most often used to determine presence or absence of receptor in breast carcinoma to guide hormonal therapy.

PSA: is expressed by cells of prostatic lineage.

Prostein (p501s): is expressed by both benign and neoplastic prostate tissue, whereas it has not been detected in any other normal or malignant tissue.

Racemase (p504s):  expression is found in prostatic adenocarcinomas but not in benign prostatic acini.  It has also been found in premalignant lesions of the prostate:  high-grade prostatic intraepithelial neoplasia (PIN) and atypical adenomatous hyperplasia.  p504s can be used as a positive marker for PIN and has been shown to stain numerous other types of carcinoma: hepatoma, breast carcinoma, pancreatic islet tumor, and desmoplastic small round cell tumor.

Renal Cell Carcinoma (RCC): is a marker for primary and metastatic renal (clear cell, conventional) carcinomas. May be negative in high-grade clear cell carcinomas.

S100: is expressed by cells of normal and abnormal neuronal/neuroendocrine lineage. It is a sensitive marker for melanoma, but many non-melanocytic tumors also show S100 immunoreactivity.

Smooth Muscle Actin: is a marker of muscle, muscle derived cells and tumors of muscle origin.

SOX-10:  is a nuclear transcription factor that participates in neural crest development and in the specification and differentiation of cells of melanocytic lineage.  A sensitive marker of melanoma, including conventional, spindled and desmoplastic subtypes.  It is superior to all other immunostains in detecting residual invasive and in situ melanoma.

Synaptophysin: is expressed in normal neuroendocrine cells and neuroendocrine neoplasms.

Terminal Deoxynucleotidyl Transferase (TdT):  is useful in differentiating primary adenocarcinoma of the lung from metastatic carcinomas originating in organs rather than thyroid, germ cell tumors, and malignant mesothelioma. It is also seen and thyroid and thyroid-derived tumors. 

Thyroglobulin: is a marker for hyperplastic and neoplastic thyroid.

Thyroid Transcription Factor (TTF-1): is expressed by tumors of the lung and thyroid.

Treponema Pallidum: stains the microorganism associated with syphilis.

Varicella Zoster Virus: causes chickenpox and shingles.  Affected skin can be difficult to distinguish from herpes simplex virus so this test becomes useful for this purpose.  

Vimentin: is a marker for cells of mesenchymal origin in normal and neoplastic tissues.

Wilms Tumor-1 (WT-1): has been identified in proliferative mesothelial cells, malignant mesothelioma, ovarian cystadenocarcinoma, gonadoblastoma, nephroblastoma, and desmoplastic small round cell tumor.  Lung adenocarcinomas rarely stain positive with this antibody.