Category Archives: Antibody List

CD Markers, Antibody List

CD30

CD30 (Ki-1 antigen) is a member of the tumor necrosis receptor factor family (TNRF) and is not a specific marker.  CD30 will mark activated benign lymphoid cells in addition to several characteristic lymphoproliferative disease subtypes (e.g. Classical Hodgkin lymphoma and anapestic large cell lymphoma) of both B-cell and T-cell lineages.
CD30 Expression Pattern
  • Benign “Activated” lymphoid cells
  • EBV-driven lymphoproliferative disorders and reactive proliferations (e.g. mononucleosis)
  • Classical Hodgkin Lymphoma
  • Anaplastic Large Cell Lymphoma (ALK+/ALK-)
  • Peripheral T-cell Lymphomas (subset)
  • Diffuse Large B-cell Lymphoma (subset)
  • Primary Mediastinal Large B-Cell Lymphoma
  • Embryonal Carcinoma
  • Germ Cell Tumors
 CD30 is an “activation” marker on T and B cells.  This marker is most often used in the work-up of cases of Hodgkin lymphoma, anaplastic large cell lymphoma (ALCL), and embryonal carcinoma.  The staining pattern has a membraneous and Golgi pattern.  B5 fixative has negative impact on staining.  CD30 is also helpful in the diagnosis of mediastinal large B cell lymphoma (focal/patchy and dim staining).
 
Unfortunately, CD30 lacks specificity, and in addition to the staining pattern in normal cells compartments, it may also be expressed in a variety of disease processes including:  peripheral T-cell lymphoma (occasional), primary effusion lymphoma, cutaneous CD30+ lymphoproliferative disorders, DLBCL (variable, focal), plasmablastic lymphoma, sinonasal NK/T cell lymphoma, embryonal carcinoma of the testis (100%), Yolk sac tumors (24%), &  mesothelioma (rare).
 
Nodular LP Hodgkin lymphoma, Adult T cell leukemia/lymphoma, pre B ALL, and systemic mastocytosis should not express CD30.
CD30+ DLBCL
Cases of DLBCL which co-express CD30 (~14%, n=903) had a more favorable 5-year survival (79% vs. 59%) in both germinal center and activated B-cell phenotypes.  Gene expression profiling (GEP) revealed down regulation of proliferation and B-cell receptor signaling with up regulation of nuclear factor kappaB activation and lymphocyte survival.  CD30+ EBV+ DLBCLis a unique subset of lymphomas with an aggressive clinical course.  The WHO classification separates EBV+ cases into a separate category.
 
CD30+ Diffuse Large B-Cell Lymphoma
CD30 expression in a diffuse large B-cell lymphoma. CD30+ cases are associated with a relatively good prognosis (excluding EBV+ cases).
CD30/PAX -5 - Classical Hodgkin Lymphoma
CD30 (red) showing variable expression and co-expression of PAX-5 (variable dim brown nuclear expression) in classical Hodgkin lymphoma
CD30 - Classical Hodgkin Lymphoma
CD30 expression in classical Hodgkin lymphoma (CHL).
CD30 - ALCL
Anaplastic Large Cell Lymphoma (ALCL) with strong diffuse expression of CD30.
Clinical Significance
Brentuximab vedotin (Adcetris®) is an anti-CD30 monoclonal antibody used to treat anaplastic large cell lymphoma and relapsed or refractory Hodgkin lymphoma.  Ongoing research with promise is active in other CD30 positive neoplastic processes.
References
Wick, MR. “Immunohistochemical approaches to the diagnosis of undifferentiated malignant tumor.”Annals of Diagnostic Pathology12(2008):72-84.
 
Bone Marrow IHC.  Torlakovic, EE, et. al. American Society for Clinical Pathology Pathology Press © 2009.  pp. 78-79.
 
Hu S, Xu-Monette ZY, Balasubramanyam A, Manyam GC, Visco C, Tzankov A, et al. CD30 expression defines a novel subgroup of diffuse large B-cell lymphoma with favorable prognosis and distinct gene expression signature: a report from the International DLBCL Rituximab-CHOP Consortium Program Study. Blood. 2013;121: 2715–2724. doi:10.1182/blood-2012-10-461848
 
Ansell SM. Brentuximab vedotin. Blood. 2014. doi:10.1182/blood-2014-06
CD Markers, Antibody List

CD25

CD25 is an IL-2 receptor.  CD25 is most often used as a marker for hairy cell leukemia, systemic mastocytosis, and adult T cell leukemia/lymphoma.  CD25 may stain activated B and T cells and cases of lymphoplasmacytic lymphoma (LPL).  CD25 is similar to CD30 in that it is an “activation” marker, and not specific.  Macrophages, and osteoblasts also often express CD25.
 
Non-neoplastic mast cells, marginal zone B cell lymphoma, T cell large granular leukemia/lymphoma, and variant hairy cell leukemia are usually negative for CD25.
CD25 Expression Pattern
Photomicrographs
CD25 expression in systemic mastocytosis.
CD25 expression in systemic mastocytosis.
CD25 expression in systemic mastocytosis.
References
Bone Marrow IHC.  Torlakovic, EE, et. al. American Society for Clinical Pathology Pathology Press © 2009.  pp. 75-76.
 
Diagnostic Immunohistochemistry:  Theranostic and Genomic Applications [edited by] David J. Dabbs. 3rd Edition.  pp. 165.
 
Lin, P., Molina, T. J., Cook, J. R., & Swerdlow, S. H. (2011). Lymphoplasmacytic lymphoma and other non-marginal zone lymphomas with plasmacytic differentiation. American Journal of Clinical Pathology, 136(2), 195–210. doi:10.1309/AJCP8FOIVTB6LBER
 
Karube, K., Suzumiya, J., Okamoto, M., Takeshita, M., Maeda, K., Sakaguchi, M., et al. (2007). Adult T-cell lymphoma/leukemia with angioimmunoblastic T-cell lymphomalike features: Report of 11 cases. The American Journal of Surgical Pathology, 31(2), 216–223. doi:10.1097/01.pas.0000213325.79368.2c
 
Siegert, S. I., Diebold, J., Ludolph-Hauser, D., & Löhrs, U. (2004). Are gastrointestinal mucosal mast cells increased in patients with systemic mastocytosis? American Journal of Clinical Pathology, 122(4), 560–565. doi:10.1309/2880-LF7Q-6XK3-HA3Q
 
Lin, P., & Medeiros, L. J. (2005). Lymphoplasmacytic lymphoma/waldenstrom macroglobulinemia: an evolving concept. Advances in Anatomic Advances in Anatomic Pathology, 12(5), 246–255. 
CD Markers, Antibody List

CD23

CD23 is a transmembrane glycoprotein expressed by different hematopoietic cells and is a low-affinity receptor for IgE.  It is also involved in promoting survival of B-cells in the germinal center.  CD23 is useful as a follicular cell dendritic cell marker and is classically expressed in cases of CLL/SLL.  CD23 has been identified in many types of lymphomas, but is most commonly used to differentiate between CLL/SLL (CD23+) and mantle cell lymphoma (CD23-).  This testing is typically performed by flow cytometry, but immunohistochemisty for CD23 is available.  Expression of CD23 has been associated with better prognosis (at least in limited published data) in follicular lymphoma, CLL/SLL, mantle cell lymphoma, and diffuse large B-cell lymphoma dependent upon expression characteristics.  CD23 is not commonly performed/used as a prognostic marker for B-cell lymphomas.
 
Rarely CD23 may be expressed in cases of Hairy cell leukemia (17%) and DLBCL (16%).  Approximately 70% of Mediastinal large B-cell lymphoma cases express CD23.  Practically, this IHC marker is used as a follicular dendritic cell marker and to help differentiate CLL/SLL from mantle cell lymphoma.  Follicular dendritic cell tumors will also express CD23 like CD21.  CD21 is more sensitive compared to CD23 as a follicular dendritic marker.
 
Follicular Lymphoma (FL) – CD23 has been found to be expressed in some cases of FL, especially from inguinal lymph nodes, and prognosis appears comparatively better.   Olteanuet. al found that 87% of inguinal lymph nodes expressed CD23, compared to 61% from other sites, and that survival was prolonged more in CD23+ cases. 
 
Diffuse Large B-Cell Lymphoma – A subset of DLBCLs may express CD23, which may have a better prognosis (CD23 is not commonly performed for this purpose).
 
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) – CD23 expression is characteristic of CLL/SLL, particularly in comparison to another CD5+ lymphoma, mantle cell lymphoma.  Strong membrane expression has been associated with a better outcome.  DiRaimondo,et. al found ~6% of CLL cases to be CD23 negative (flow cytometry), and they had a worse prognosis.  Many of these cases may have been misdiagnosed mantle cell lymphomas.
 
Mantle Cell Lymphoma (MCL) – CD23 is characteristically negative in MCL, which helps to differentiate it from CLL/SLL.  However, ~21% of cases of MCL were found to be CD23+ by Gao,et. al, and other studies have shown CD23 expression in MCL ranging from 0% to 45% (most data appears to be based on flow cytometry).
CD23 Expression Pattern
  • CLL/SLL – characteristically expressed (6% may be negative, probably much lower)
  • Mantle cell lymphoma may be CD23+ (21%+, 0-45%)
  • B-cell Lymphomas (e.g. some DLBCL and follicular lymphomas may show expression)
  • Follicular Dendritc Cells (not as sensitive as CD21)
  • B-cells in mantle zone of lymphoid follicles
Photomicrographs

CD23 - Tonsil
CD23 expression highlighting follicular dendritic meshwork in a normal tonsil.

Reference
Bone Marrow IHC.  Torlakovic, EE, et. al. American Society for Clinical Pathology Pathology Press © 2009.  pp. 69.
 
Linderoth J, Jerkeman M, Cavallin-Stahl E, et al. Immunohistochemical expression of CD23 and CD40 may identify prognostically favorable subgroups of diffuse largeB-cell lymphoma: a Nordic Lymphoma Group Study.ClinCancer Res.2003;9:722-728.
 
Olteanu H, Fenske TS, Harrington AM, Szabo A, He P, Kroft SH. CD23 Expression in Follicular Lymphoma: Clinicopathologic Correlations. Am J Clin Pathol. 2011;135: 46–53. doi:10.1309/AJCP27YWLIQRAJPW
 
Gao J, Peterson L, Nelson B, Goolsby C, Chen Y-H. Immunophenotypic variations in mantle cell lymphoma. Am J Clin Pathol. 2009;132: 699–706. doi:10.1309/AJCPV8LN5ENMZOVY
 
Troxell ML, Schwartz EJ, van de Rijn M, Ross DT, Warnke RA, Higgins JP, et al. Follicular dendritic cell immunohistochemical markers in angioimmunoblastic T-cell lymphoma. Appl Immunohistochem Mol Morphol. 2005;13: 297–303.
 
Dalton RR, Admirand JH, Medeiros LJ. Small Lymphocytic Lymphoma. Pathology Case Reviews. 2004;9: 7.
 
DiRaimondo F, Albitar M, Huh Y, O’Brien S, Montillo M, Tedeschi A, et al. The clinical and diagnostic relevance of CD23 expression in the chronic lymphoproliferative disease. Cancer. 2002;94: 1721–1730. doi:10.1002/cncr.10401
Antibody List, N - Z Antibodies

ZAP-70

General
ZAP-70 (zeta-associated protein-70) is a surrogate marker for the somatic mutation status of immunoglobulin heavy chain (IGHV) in CLL.  Unfortunately, attempts to utilize flow cytometry for this purpose has resulted in unreliable results.  ZAP-70 expression by IHC has been shown to have an increased risk of progression to therapy requirement (3-yr risk 83% vs. 31% for ZAP-70 negative) [Modern Pathology (2010)23,1518-1523].  ZAP-70 expression is not specific to CLL, and is not particularly useful for tumor sub-classification/prognosis outside the setting of CLL.
 
ZAP-70 expression in B-cell lymphoid neoplasms (Carreras, J, et al).
Lymphoid Disorder
No.
ZAP-70 + (%)
Lymphoblastic Lymphoma
7
28%
Chronic Lymphocytic Leukemia
52
65%
Mantle Cell Lymphoma
36
8%
     Classical
28
11%
     Blastoid
8
0%
Follicular Lymphoma
19
0%
Marginal Zone Lymphoma
23
4%
     MALT
11
0%
     Nodal
5
20%
     Splenic
7
0%
Diffuse Large B-Cell Lymphoma
45
2%
Burkitt Lymphoma
29
31%
Hodgkin Lymphoma
14
0%
Stain Interpretation
ZAP-70 is interpreted as negative or positive.  The minimum positive expression is weakly positive( 1+) staining defined as granular cytoplasmic staining with nuclear blush in a majority of tumor cells.  Strong positivity (2+) is  defined as strong expression in a majority of tumor cells.
 
ZAP-70 will also stain T-cells in the background.  Therefore, ZAP-70 should be interpreted with the accompaniment of CD3 and CD20, so that there is clear discernment between tumor and background lymphoid cells.
 
IHC on Peripheral Blood
One of the big problems to identify ZAP-70 expression in CLL is the material available for evaluation.  Most material is based on peripheral blood, and flow cytometry has been difficult to analyze reliably for ZAP-70 expression.  An alternative is to perform PERIPHERAL BLOOD MONONUCLEAR CELL (PBMC) PURIFICATION AND CELL BLOCK PREPARATION as described by Roullet, et. al. in which a cell block is prepared from peripheral blood on which IHC for ZAP-70 can be reliably performed.  Please review Roullet’s article for complete technical details.
Photomicrographs

ZAP-70 - Benign Tonsil
ZAP-70 – Benign Tonsil

ZAP-70 CLL/SLL
ZAP-70 weak expression in CLL with an unmutated IgVH gene (poor prognosis). Strong staining in background T-cells.

ZAP-70 CLL/SLL
ZAP-70 weak expression in CLL with an unmutated IgVH gene (poor prognosis)

References
Admirand, J. H., Knoblock, R. J., Coombes, K. R., Tam, C., Schlette, E. J., Wierda, W. G., et al. (2010). Immunohistochemical detection of ZAP70 in chronic lymphocytic leukemia predicts immunoglobulin heavy chain gene mutation status and time to progression. Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc, 23(11), 1518–1523. doi:10.1038/modpathol.2010.131 
 
Carreras, J., Villamor, N., Colomo, L., Moreno, C., Ramón y Cajal, S., Crespo, M., et al. (2005). Immunohistochemical analysis of ZAP-70 expression in B-cell lymphoid neoplasms. The Journal of Pathology, 205(4), 507–513. doi:10.1002/path.1727
 
Roullet, M., Sargent, R., Pasha, T., Cajiao, I., Elstrom, R., Smith, T., et al. (2007). ZAP70 expression assessed by immunohistochemistry on peripheral blood: a simple prognostic assay for patients with chronic lymphocytic leukemia. Applied Immunohistochemistry & Molecular Morphology : AIMM / Official Publication of the Society for Applied Immunohistochemistry, 15(4), 471–476. doi:10.1097/01.pai.0000213152.41440.34 
 
Crespo, M., Bosch, F., Villamor, N., Bellosillo, B., Colomer, D., Rozman, M., et al. (2003). ZAP-70 expression as a surrogate for immunoglobulin-variable-region mutations in chronic lymphocytic leukemia. The New England Journal of Medicine, 348(18), 1764–1775. doi:10.1056/NEJMoa023143 
Antibody List, N - Z Antibodies

WT-1 (Wilms tumor gene product)

WT-1 (Wilms tumor gene product) is a marker most commonly used to identify OVARIAN SEROUS CARCINOMAS.  It is also commonly used in a panel to differentiate mesothelioma (positive) from adenocarcinoma (negative).  WT-1 has a normal expression distribution in adult tissues, which includes Sertoli cells, ovarian stromal and surface epithelium, and mesothelium.  The 6F-H2 clone has shown better sensitivity compared to other WT-1 antibodies (Ordonez).
 
Tumors / lesions expressing WT-1:
  • Mesothelioma (>75% of epithelial mesotheliomas, usually negative in sarcomatoid variants)
  • Ovarian Serous Carcinomas
  • Wilms tumor
  • Desmoplastic Small Round Cell Tumors
  • Metanephric Adenomas
 
Tumor
Expression (%)
Ovarian Serous Carcinoma
93%
Ovarian Mucinous Carcinoma
0%
Pancreatobiliary Carcinoma
0%
Breast Carcinoma
0%
Lung Carcinoma
0%
Colon Adenocarcinoma
0%
Renal Cell Carcinoma
0%
Thyroid Carcinoma
0%
Prostate Adenocarcinoma
0%
 
WT-1 expression in differentiating mesothelioma from adenocarcinoma (Marchevsky).
Tumor
Expression (%)
Epithelioid Mesothelioma
77%
Sarcomatoid Mesothelioma
13%
Adenocarcnioma
4%
Photomicrographs

WT-1 - Wilms Tumor
WT-1 – Wilms Tumor

WT-1 - Mesothelioma
WT-1 – Mesothelioma

WT-1 - Ovarian Serous Carcinoma
WT-1 – Ovarian Serous Carcinoma

WT-1 - Stromal Cells
WT-1 expression in stromal cells.

 
References:
Muir, T. E., Cheville, J. C., & Lager, D. J. (2001). Metanephric adenoma, nephrogenic rests, and Wilms’ tumor: a histologic and immunophenotypic comparison. The American Journal of Surgical Pathology, 25(10), 1290–1296.
 
Marchevsky, A. M. (2008). Application of immunohistochemistry to the diagnosis of malignant mesothelioma. Archives of Pathology & Laboratory Medicine, 132(3), 397–401.
 
Ordóñez, N. G. (2005). Immunohistochemical diagnosis of epithelioid mesothelioma: an update. Archives of Pathology & Laboratory Medicine, 129(11), 1407–1414.  
  
Hadi, AIMM Annual Meeting, “Carcinomas of Unknown Primary”, presentation, 2011.
Antibody List, N - Z Antibodies

Villin

Villin is an actin-binding protein found in microvilli.  It’s expression pattern is cytoplasmic and generally restricted to epithelial cells in the GI tract.  It is a sensitive marker for colon adenocarcinomas, but not entirely specific.  It also stains renal proximal tubules and hepatic bile ducts.
 
CDX-2 and Villin expression in human tumors (2-3+ expression) (Werling, R.W., et. al.)
Tumor Type
No.
CDX2
Villin
G.I. Tract
 
 
 
Colon Adenocarcinoma
75
99%
82% (n=73)
Duodenal Adenoma
10
100%
100%
Gastric Adenocarcinoma
24
70%
42%
Esophageal Adenocarcinoma
9
67%
78%
Pancreatic Adenocarcinoma
22
32%
40%
Cholangiocarcinoma/GB
16
25%
60%
Hepatocellular Carcinoma
12
0%
0%
Carcinoid Tumors
12
42%
34%
Ovary
 
 
 
Mucinous Adenocarcinoma
14
64%
64%
Mucinous Cystadenoma
13
8%
0%
Mucinous Borderline Tumor
4
25%
0%
Non-Mucinous
36
0%
0% (n=31)
Genitourinary Tract
 
 
 
Urothelial Carcinoma
21
0%
0%
Adenocarcinoma
2
100%
100%
Urachal Caricinoma
1
100%
100%
Renal Cell Carcinoma
7
0%
0% (n=3)
Prostate Adenocarcinoma
27
4%
0% (n=24)
Breast Carcinoma
34
0%
0%
Lung (45 primary; 18 met)
63
0%
5%
Adenocarcinoma
11
0%
0%
Squamous Cell Carcinoma
11
0%
0%
Non-Small Cell Carcinoma NOS
33
0
9%
Mucinous Carcinoma
2
0%
0%
Small Cell Carcinoma
4
0%
0%
Mesothelioma
7
0%
0%
Head and Neck
 
 
 
Thyroid
36
3%
0%
Papillary Carcinoma
11
9%
0%
Follicular Adenoma/Carcinoma
25
0%
0%
Salivary Gland
12
0%
0%
Mixed Tumor
6
0%
0%
Low Grade Carcinoma
6
0%
0%
Squamous Cell Carcinoma
13
0%
0% (n=11)
Photomicrographs

Villin - Colon Adenocarcinoma
Villin – Colon Adenocarcinoma

Villin - Colon
Villin – Colon

Villin - Colon Adenocarcinoma
Villin – Colon Adenocarcinoma

References: 
Gastroenterol94:343-52, 1988. 
 
Hadi, AIMM Annual Meeting, “Carcinomas of Unknown Primary”, presentation, 2011.
 
Werling, R. W., Yaziji, H., Bacchi, C. E., & Gown, A. M. (2003). CDX2, a highly sensitive and specific marker of adenocarcinomas of intestinal origin: an immunohistochemical survey of 476 primary and metastatic carcinomas. The American Journal of Surgical Pathology, 27(3), 303–310.  
Antibody List, N - Z Antibodies

TTF-1

TTF-1 is a nuclear transcription factor that is expressed in thyroid and respiratory epithelium.  It is a useful marker for lung adenocarcinomas and thyroid malignancies.  In the setting of neuroendocrine carcinomas, TTF-1 expression is not specific as to the site of origin, except that Merkel cell carcinomas of the skin do not usually express TTF-1 (some have reported focal expression).  The expression pattern of TTF-1, like other transcription markers, is generally strong and diffuse.  Lower levels of positivity should bring caution to the interpretation.
 
TTF-1 use has become more important to sub-classify lung tumors on small biopsy specimens.  It is generally considered the most sensitive and specific individual marker for lung adenocarcinomas, but is often used in combination with Napsin A to maximize sensitivity and specificity for the determination of primary lung adenocarcinomas.  Current recommendations are to test non-small cell lung carcinomas (non-squamous cell carcinoma) for ALK, ROS-1 and EGFR mutations, as targeted therapies are available (this list is ever expanding and should be verified with current medical literature).

Continue reading TTF-1 →

Antibody List, N - Z Antibodies

Thyroglobulin

Thyroglobulin is a glycoprotein expressed by thyroid follicular cells.  It is a specific marker for thyroid derivation, and may be useful in the work-up of carcinomas of unknown primary.  It may be less sensitive in less differentiated thyroid tumors, as anapestic thyroid carcinoma is notorious for not staining with about anything.
 
Pitfalls
  • Medullary thyroid carcinoma does not express thyroglobulin.
  • Thyroglobulin can have a lot of artifactual staining, which may cause difficultly diagnosing tumors like medullary carcinoma (expected to be thyroglobulin negative).
  • Dedifferentiated thyroid tumors may not express thyroglobulin.
Photomicrographs

Thyroglobulin - Follicular Carcinoma of Thyroid
Thyroglobulin – Follicular Carcinoma of Thyroid

Thyroglobulin - Follicular Carcinoma of Thyroid
Thyroglobulin – Follicular Carcinoma of Thyroid

References:
 
Fischer, S., & Asa, S. L. (2008). Application of immunohistochemistry to thyroid neoplasms. Archives of Pathology & Laboratory Medicine, 132(3), 359–372. 
Antibody List, N - Z Antibodies

Terminal Deoxynucleotiyl Transferase (TdT)

Terminal deoxynucleotiyl transferase (TdT) is a nuclear transcription factor expressed in B and T-cell precursors and cortical thymocytes.  It is expressed in acute lymphoblastic lymphoma (95%), AML (<25%), Merkel cell carcinoma (~50%), hematogones, and thymomas.  It is negative in Burkitt lymphoma.
 
Scattered TdT positive cells in benign lymphoid tissue (e.g. tonsil) is a common finding.
 
TdT Expression Pattern
Photomicrographs

TdT - Benign Tonsil
Scattered staining TdT positive cells in normal tonsil tissue.

TdT - Thymoma
TdT – Thymoma

TdT - T-ALL
TdT – T-ALL

References:
Bone Marrow IHC.  Torlakovic, EE, et. al. American Society for Clinical Pathology Pathology Press © 2009.  pp. 167.
 
Sidiropoulos, M., Hanna, W., Raphael, S. J., & Ghorab, Z. (2011). Expression of TdT in Merkel cell carcinoma and small cell lung carcinoma. American Journal of Clinical Pathology, 135(6), 831–838. doi:10.1309/AJCPLCB2Q9QXDZAA 
 
Onciu, M., Lorsbach, R. B., Henry, E. C., & Behm, F. G. (2002). Terminal deoxynucleotidyl transferase-positive lymphoid cells in reactive lymph nodes from children with malignant tumors: incidence, distribution pattern, and immunophenotype in 26 patients. American Journal of Clinical Pathology, 118(2), 248–254. doi:10.1309/L3UW-3AE7-L4LB-3QX3
 
Strauchen, J. A., & Miller, L. K. (2001). Terminal deoxynucleotidyl transferase-positive cells in human tonsils. American Journal of Clinical Pathology, 116(1), 12–16. doi:10.1309/M8V2-DWPB-DVX1-UBPC  
 
Hurford, M. T., Altman, A. J., Digiuseppe, J. A., Sherburne, B. J., & Rezuke, W. N. (2008). Unique Pattern of Nuclear TdT Immunofluorescence Distinguishes Normal Precursor B Cells (Hematogones) From Lymphoblasts of Precursor B-Lymphoblastic Leukemia. American Journal of Clinical Pathology, 129(5), 700–705. doi:10.1309/ANERT51H38TUEC45 
Antibody List, N - Z Antibodies

TFE3 (transcription factor E3)

TFE3 (transcription factor E3) is a gene located on chromosome Xp11.2, and is a member of the microphthalmia-associated transcription factor (MITF) family.  Translocations with this gene are associated with different partners in  alveolar soft part sarcoma and a subset of renal cell carcinomas (Xp11.2 translocation RCC).  TFE3 protein over expression can be detected by IHC in cases with a TFE3 translocation, and the expression is nuclear.  The normal gene product (non-TFE3 translocation cases) is not detectable by IHC.
 
In a large case set (1476 cases) by Argani, et. al., TFE3 expression was demonstrated in 1/2 high-grade myxofibrosarcomas, 3/60 adrenal cortical carcinomas, and 1/15 distal bile duct carcinomas.  TFE3 is a sensitive and specific marker for alveolar soft part sarcoma and Xp11.2 RCC, as it appears to be expressed in >90% of Xp11.2 translocation associated renal cell carcinomas and alveolar soft part sarcoma.
 
Xp11.2 RCC cases tend to express E-cadherin and CD10, while NOT expressing CK7 and EMA.  Conventional clear cell RCC tend not to express E-cadherin while expressing EMA.
Photomicrographs

Xp11.2 Renal Cell Carcinoma
Xp11.2 Renal Cell Carcinoma – H&E section

TFE3 - Xp11.2 Renal Cell Carcinoma
TFE3 – Xp11.2 Renal Cell Carcinoma

TFE3 - Xp11.2 Renal Cell Carcinoma
TFE3 – Xp11.2 Renal Cell Carcinoma

References:

Camparo, P., Vasiliu, V., Molinie, V., Couturier, J., Dykema, K. J., Petillo, D., et al. (2008). Renal translocation carcinomas: clinicopathologic, immunohistochemical, and gene expression profiling analysis of 31 cases with a review of the literature. The American Journal of Surgical Pathology, 32(5), 656–670. doi:10.1097/PAS.0b013e3181609914
 
Argani, P., Lal, P., Hutchinson, B., Lui, M. Y., Reuter, V. E., & Ladanyi, M. (2003). Aberrant nuclear immunoreactivity for TFE3 in neoplasms with TFE3 gene fusions: a sensitive and specific immunohistochemical assay. The American Journal of Surgical Pathology, 27(6), 750–761.
 
Argani, P., Olgac, S., Tickoo, S. K., Goldfischer, M., Moch, H., Chan, D. Y., et al. (2007). Xp11 translocation renal cell carcinoma in adults: expanded clinical, pathologic, and genetic spectrum. The American Journal of Surgical Pathology, 31(8), 1149–1160. doi:10.1097/PAS.0b013e318031ffff
 
Argani, P., Antonescu, C. R., Couturier, J., Fournet, J.-C., Sciot, R., Debiec-Rychter, M., et al. (2002). PRCC-TFE3 renal carcinomas: morphologic, immunohistochemical, ultrastructural, and molecular analysis of an entity associated with the t(X;1)(p11.2;q21). The American Journal of Surgical Pathology, 26(12), 1553–1566.
 
Argani, P., Lal, P., Hutchinson, B., Lui, M. Y., Reuter, V. E., & Ladanyi, M. (2003). Aberrant nuclear immunoreactivity for TFE3 in neoplasms with TFE3 gene fusions: a sensitive and specific immunohistochemical assay. The American Journal of Surgical Pathology, 27(6), 750–761.
 
Armah, H. B., & Parwani, A. V. (2010). Xp11.2 translocation renal cell carcinoma. Archives of Pathology & Laboratory Medicine, 134(1), 124–129. doi:10.1043/2008-0391-RSR.1