Immunohistochemical endothelial markers: A review

Advances in Anatomic Pathology

Volumn 19, Issue 5, 2012, Pages 281-295

  Ordóñez, Nelson G ^a  

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

Author keywords

angiosarcoma; CD31; CD34; claudin 5; endothelium; ERG; FLI 1; immunohistochemistry; Kaposi sarcoma; LMO2; podoplanin; prox1; thrombomodulin; VEGFR 2; VEGFR 3

Indexed keywords

BIOLOGICAL MARKER; CD31 ANTIGEN; CD34 ANTIGEN; CD44V ANTIGEN; CLAUDIN 5; HERMES ANTIGEN; LIM DOMAIN ONLY 2; LYMPHATIC VESSEL ENDOTHELIAL HYALURONAN 1; PODOPLANIN; PROTEIN PROX 1; THROMBOMODULIN; TRANSCRIPTION FACTOR ERG; TRANSCRIPTION FACTOR FLI 1; ULEX EUROPAEUS AGGLUTININ; UNCLASSIFIED DRUG; VASCULOTROPIN A; VASCULOTROPIN RECEPTOR 2; VASCULOTROPIN RECEPTOR 3; VON WILLEBRAND FACTOR;

AMINO TERMINAL SEQUENCE; ANGIOSARCOMA; CELL ADHESION; CELL DIFFERENTIATION; CELL INVASION; CELL MIGRATION; ENDOTHELIUM CELL; EWING SARCOMA; GLYCOSYLATION; HEMANGIOENDOTHELIOMA; HEMANGIOMA; HUMAN; IMMUNOHISTOCHEMISTRY; IMMUNOREACTIVITY; KAPOSI SARCOMA; MESOTHELIOMA; MOLECULAR WEIGHT; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; SQUAMOUS CELL CARCINOMA; SYNCYTIOTROPHOBLAST; TRANSITIONAL CELL CARCINOMA;

BLOOD VESSELS; ENDOTHELIUM, LYMPHATIC; ENDOTHELIUM, VASCULAR; HUMANS; IMMUNOHISTOCHEMISTRY; LYMPHATIC VESSELS; TUMOR MARKERS, BIOLOGICAL; VASCULAR NEOPLASMS;

EID: 84865488056     PISSN: 10724109     EISSN: 15334031     Source Type: Journal    
DOI: 10.1097/PAP.0b013e3182691c2a     Document Type: Review

References (175)

1. Newman PJ, Berndt MC, Gorski J, et al. PECAM-1 (CD31) cloning and relation to adhesion molecules of the immunoglobulin gene superfamily. Science. 1990;247:1219-1222.
2. DeLisser HM, Christofidou-Solomidou M, Strieter RM, et al. Involvement of endothelial PECAM-1/CD31 in angiogenesis. Am J Pathol. 1997;151:671-677. (Pubitemid 27385598)
3. O'Brien CD, Lim P, Sun J, et al. PECAM-1-dependent neutrophil transmigration is independent of monolayer PECAM-1 signaling or localization. Blood. 2003;101:2816-2825. (Pubitemid 36857649)
4. Coukos G, Makrigiannakis A, Amin K, et al. Plateletendothelial cell adhesion molecule-1 is expressed by a subpopulation of human trophoblasts: a possible mechanism for trophoblast-endothelial interaction during haemochorial placentation. Mol Hum Reprod. 1998;4:357-367. (Pubitemid 28228532)
5. Rosso R, Lucioni M. Normal and neoplastic cells of brown adipose tissue express the adhesion molecule CD31. Arch Pathol Lab Med. 2006;130:480-482.
6. Mentzel T, Partanen TA, Kutzner H. Hobnail hemangioma ("targetoid hemosiderotic hemangioma"): clinicopathologic and immunohistochemical analysis of 62 cases. J Cutan Pathol. 1999;26:279-286. (Pubitemid 29373925)
7. Neuhauser TS, Derringer GA, Thompson LD, et al. Splenic angiosarcoma: a clinicopathologic and immunophenotypic study of 28 cases. Mod Pathol. 2000;13:978-987.
8. Gratzinger D, Zhao S, West R, et al. The transcription factor LMO2 is a robust marker of vascular endothelium and vascular neoplasms and selected other entities. Am J Clin Pathol. 2009;131:264-278.
9. Rimella Le Huu A, Jokinen CH, Rubin BP, et al. Expression of prox1, lymphatic endothelial nuclear transcription factor, in Kaposiform hemangioendothelioma and tufted angioma. Am J Surg Pathol. 2010;34:1563-1573.
10. Mentzel T, Beham A, Calonje E, et al. Epithelioid hemangioendothelioma of skin and soft tissues: clinicopathologic and immunohistochemical study of 30 cases. Am J Surg Pathol. 1997;21:363-374. (Pubitemid 27184768)
11. Makhlouf HR, Ishak KG, Goodman ZD. Epithelioid hemangioendothelioma of the liver: a clinicopathologic study of 137 cases. Cancer. 1999;85:562-582. (Pubitemid 29075278)
12. Weinreb I, Cunningham KS, Perez-Ordoñez B, et al. CD10 is expressed in most epithelioid hemangioendotheliomas: a potential diagnostic pitfall. Arch Pathol Lab Med. 2009;133:1965-1968.
13. Parums DV, Cordell JL, Micklem K, et al. JC70: a new monoclonal antibody that detects vascular endothelium associated antigen on routinely processed tissue sections. J Clin Pathol. 1990;43:752-757. (Pubitemid 20279705)
14. DeYoung BR, Wick MR, Fitzgibbon JF, et al. CD31: an immunospecific marker for endothelial differentiation in human neoplasms. Appl Immunohistochem. 1993;1:97-100.
15. Miettinen M, Lindenmayer AE, Chaubal A. Endothelial cell markers CD31, CD43 and BNH9 antibody to H-and Y-antigens-evaluation of their specificity and sensitivity in the diagnosis of vascular tumors and comparison with von Willebrand factor. Mod Pathol. 1994;7:82-90.
16. Ohsawa M, Naka N, Tomita Y, et al. Use of immunohistochemical procedures in diagnosing angiosarcoma: evaluation of 98 cases. Cancer. 1995;75:2867-2874.
17. Orchard GE, Zelger B, Jones EW, et al. An immunocytochemical assessment of 19 cases of cutaneous angiosarcoma. Histopathology. 1996;28:235-240. (Pubitemid 26091914)
18. Breiteneder-Geleff S, Soleiman A, Kowalski H, et al. Angiosarcomas express mixed endothelial phenotypes of blood and lymphatic capillaries: podoplanin as a specific marker for lymphatic endothelium. Am J Pathol. 1999;154:385-394. (Pubitemid 29094089)
19. Folpe AL, Veikkola T, Valtola R, et al. Vascular endothelial growth factor receptor-3 (VEGFR-3): a marker of vascular tumors with presumed lymphatic differentiation, including Kaposi's sarcoma, kaposiform and Dabska-type hemangioendotheliomas, and a subset of angiosarcomas. Mod Pathol. 2000;13:180-185. (Pubitemid 30109106)
20. Kahn HJ, Bailey D, Marks A. Monoclonal antibody D2-40, a new marker of lymphatic endothelium, reacts with Kaposi's sarcoma and a subset of angiosarcomas. Mod Pathol. 2002;15:434-440. (Pubitemid 34326952)
21. Deshpande V, Rosenberg AE, O'Connell JX, et al. Epithelioid angiosarcoma of the bone: a series of 10 cases. Am J Surg Pathol. 2003;27:709-716. (Pubitemid 36617507)
22. Higgins JPT, Montgomery K, Wang L, et al. Expression of FKBP12 in benign and malignant vascular endothelium: an immunohistochemical study on conventional sections and tissue microarrays. Am J Surg Pathol. 2003;27:58-64. (Pubitemid 36014899)
23. Allison KH, Yoder BJ, Bronner MP, et al. Angiosarcoma involving the gastrointestinal tract: a series of primary and metastatic cases. Am J Surg Pathol. 2004;28:298-307. (Pubitemid 38269563)
24. Weninger W, Partanen TA, Breiteneder-Geleff S, et al. Expression of vascular endothelial growth factor receptor-3 and podoplanin suggests a lymphatic endothelial cell origin of Kaposi's sarcoma tumor cells. Lab Invest. 1999;79:243-251. (Pubitemid 29110654)
25. Lyons LL, North PE, Mac-Moune Lai F, et al. Kaposiform hemangioendothelioma: a study of 33 cases emphasizing its pathologic, immunophenotypic, and biologic uniqueness from juvenile hemangioma. Am J Surg Pathol. 2004;28:559-568. (Pubitemid 38579556)
26. Debelenko LV, Perez-Atayde AR, Mulliken JB, et al. D2-40 immunohistochemical analysis of pediatric vascular tumors reveals positivity in kaposiform hemangioendothelioma. Mod Pathol. 2005;18:1454-1460. (Pubitemid 41509400)
27. Fanburg-Smith JC, Michal M, Partanen TA, et al. Papillary intralymphatic angioendothelioma (PILA): a report of twelve cases of a distinctive vascular tumor with phenotypic features of lymphatic vessels. Am J Surg Pathol. 1999;23:1004-1010. (Pubitemid 29409761)
28. Paal E, Thompson LD, Heffess CS. A clinicopathologic and immunohistochemical study of ten pancreatic lymphangiomas and a review of the literature. Cancer. 1998;82:2150-2158. (Pubitemid 28240821)
29. Brown M, Pysher T, Coffin CM. Lymphangioma and congenital pulmonary lymphangiectasis: a histologic, immunohistochemical, and clinicopathologic comparison. Mod Pathol. 1999;12:569-575. (Pubitemid 29279708)
30. Kim KM, Choi KY, Lee A, et al. Lymphangioma of large intestine: report of ten cases with endoscopic and pathologic correlation. Gastrointest Endosc. 2000;52:255-259. (Pubitemid 30650268)
31. Hornick JL, Fletcher CD. Intraabdominal cystic lymphangiomas obscured by marked superimposed reactive changes: clinicopathological analysis of a series. Hum Pathol. 2005;36:426-432. (Pubitemid 40591814)
32. Martel M, Cheuk W, Lombardi L, et al. Sclerosing angiomatoid nodular transformation (SANT): report of 25 cases of a distinctive benign splenic lesion. Am J Surg Pathol. 2004;28:1268-1279. (Pubitemid 39336366)
33. Slone SP, Fleming DR, Buchino JJ. Sinus histiocytosis with massive lymphadenopathy and Langerhans cell histiocytosis express the cellular adhesion molecule CD31. Arch Pathol Lab Med. 2003;127:341-344. (Pubitemid 36378699)
34. DeYoung BR, Frierson HF Jr, Ly MN, et al. CD31 immunoreactivity in carcinomas and mesotheliomas. Am J Clin Pathol. 1998;110:374-377. (Pubitemid 28406996)
35. Ortiz-Hidalgo C, Torres JE, Cuesta-Mejías T, et al. CD31 with strong membrane-based immunoreactivity in ductal carcinoma of the breast. Appl Immunohistochem Mol Morphol. 2000;8:334-335.
36. Lanza F, Healy L, Sutherland DR. Structural and functional features of the CD34 antigen: an update. J Biol Regul Homeost Agents. 2001;15:1-13. (Pubitemid 32492723)
37. Delia D, Lampugnani MG, Resnati M, et al. CD34 expression is regulated reciprocally with adhesion molecules in vascular endothelial cells in vitro. Blood. 1993;81:1001-1008. (Pubitemid 23054838)
38. Hirose T, Tani T, Shimada T, et al. Immunohistochemical demonstration of EMA/Glut1-positive perineurial cells and CD34-positive fibroblastic cells in peripheral nerve sheath tumors. Mod Pathol. 2003;16:293-298. (Pubitemid 36443977)
39. Pusztaszeri MP, Seelentag W, Bosman FT. Immunohistochemical expression of endothelial markers CD31, CD34, von Willebrand factor, and Fli-1 in normal human tissues. J Histochem Cytochem. 2006;54:385-395.
40. Robinson TL, Sircar K, Hewlett BR, et al. Gastrointestinal stromal tumors may originate from a subset of CD34-positive interstitial cells of Cajal. Am J Pathol. 2000;156:1157-1163. (Pubitemid 30659992)
41. Fina L, Molgaard HV, Robertson D, et al. Expression of the CD34 gene in vascular endothelial cells. Blood. 1990;75:2417-2426. (Pubitemid 20202322)
42. Greaves MF, Brown J, Molgaard HV, et al. Molecular features of CD34: a hemopoietic progenitor cell-associated molecule. Leukemia. 1992;6(suppl 1):31-36.
43. Ramani P, Bradley NJ, Fletcher CDM. QBEND/10, a new monoclonal antibody to endothelium: assessment of its diagnostic utility in paraffin sections. Histopathology. 1990;17:237-242. (Pubitemid 20275966)
44. Traweek ST, Kandalaft PL, Mehta P, et al. The human hematopoietic progenitor cell antigen (CD34) in vascular neoplasia. Am J Clin Pathol. 1991;96:25-31.
45. Fujii T, Zen Y, Sato Y, et al. Podoplanin is a useful diagnostic marker for epithelioid hemangioendothelioma of the liver. Mod Pathol. 2008;21:125-130. (Pubitemid 351172161)
46. Anthony PP, Ramani P. Endothelial markers in malignant vascular tumours of the liver: superiority of QB-END/10 over Von Willebrand factor and Ulex europaeus agglutinin 1. J Clin Pathol. 1991;44:29-32.
47. Meis-Kindblom JM, Kindblom L-G. Angiosarcoma of soft tissue: a study of 80 cases. Am JSurgPathol. 1998;22:683-697. (Pubitemid 28280270)
48. Aziza J, Mazerolles C, Selves J, et al. Comparison of the reactivities of monoclonal antibodies QBEND10 (CD34) and BNH9 in vascular tumors. Appl Immunohistochem. 1993;1:51-57.
49. Russell Jones R, Orchard G, Zelger B, et al. Immunostaining for CD31 and CD34 in Kaposi sarcoma. J Clin Pathol. 1995;48:1011-1016.
50. Rudolph P, Schubert B, Wacker HH, et al. Immunophenotyping of dermal spindle cell tumors: diagnostic value of monocyte marker Ki-M1p and histogenetic considerations. Am J Surg Pathol. 1997;21:791-800. (Pubitemid 27406549)
51. Suster S, Fisher C, Moran CA. Expression of bcl-2 oncoprotein in benign and malignant spindle cell tumors of soft tissue, skin, serosal surfaces, and gastrointestinal tract. Am J Surg Pathol. 1998;22:863-872. (Pubitemid 28328232)
52. Parfitt JR, Rodriguez-Justo M, Feakins R, et al. Gastrointestinal Kaposi's sarcoma: CD117 expression and the potential for misdiagnosis as gastrointestinal stromal tumour. Histopathology. 2008;52:816-823. (Pubitemid 351724907)
53. Zukerberg LR, Nickoloff BJ, Weiss SW. Kaposiform hemangioendothelioma of infancy and childhood: an aggressive neoplasm associated with Kasabach-Merritt syndrome and lymphangiomatosis. Am J Surg Pathol. 1993;17:321-328. (Pubitemid 23096821)
54. Renshaw AA. O13 (CD99) in spindle cell tumors: Reactivity with hemangiopericytoma, solitary fibrous tumor, synovial sarcoma, and meningioma but rarely with sarcomatoid mesothelioma. Appl Immunohistochem. 1995;3:250-256.
55. Chang Y-L, Lee Y-C, Wu C-T. Thoracic solitary fibrous tumor: clinical and pathological diversity. Lung Cancer. 1999;23:53-60. (Pubitemid 29099816)
56. Ordóñez NG. Localized (solitary) fibrous tumor of the pleura. Adv Anat Pathol. 2000;7:327-340.
57. Hasegawa T, Matsuno Y, Shimoda T, et al. Frequent expression of bcl-2 protein in solitary fibrous tumors. Jpn J Clin Oncol. 1998;28:86-91. (Pubitemid 128526026)
58. Weiss SW, Nickoloff BJ. CD-34 is expressed by a distinctive cell population in peripheral nerve, nerve sheath tumors, and related lesions. Am J Surg Pathol. 1993;17:1039-1045. (Pubitemid 23289346)
59. Arber DA, Kandalaft PL, Mehta P, et al. Vimentin-negative epithelioid sarcoma. The value of an immunohistochemical panel that includes CD34. Am J Surg Pathol. 1993;17:302-307. (Pubitemid 23085925)
60. Sirgi KE, Wick MR, Swanson PE. B72.3 and CD34 immunoreactivity in malignant epithelioid soft tissue tumors. Adjuncts in the recognition of endothelial neoplasms. Am J Surg Pathol. 1993;17:179-185. (Pubitemid 23044882)
61. Miettinen M, Fanburg-Smith JC, Virolainen M, et al. Epithelioid sarcoma: an immunohistochemical analysis of 112 classical and variant cases and a discussion of the differential diagnosis. Hum Pathol. 1999;30:934-942. (Pubitemid 29380517)
62. Monihan JM, Carr NJ, Sobin LH. CD34 immunoexpression in stromal tumours of the gastrointestinal tract and in mesenteric fibromatoses. Histopathology. 1994;25:469-473. (Pubitemid 24356790)
63. van de Rijn M, Hendrickson MR, Rouse RV. CD34 expression by gastrointestinal tract stromal tumors. Hum Pathol. 1994;25:766-771. (Pubitemid 24249234)
64. Sadler JE. Biochemistry and genetics of von Willebrand factor. Annu Rev Biochem. 1998;67:395-424. (Pubitemid 28411134)
65. Kuwano A, Morimoto Y, Nagai T, et al. Precise chromosomal locations of the genes for dentatorubral-pallidoluysian atrophy (DRPLA), von Willebrand factor (F8vWF) and parathyroid hormone-like hormone (PTHLH) in human chromosome 12p by deletion mapping. Hum Genet. 1996;97:95-98.
66. Ordóñez NG, Batsakis JG. Comparison of Ulex europaeus I lectin and factor VIII-related antigen in vascular lesions. Arch Pathol Lab Med. 1984;108:129-132. (Pubitemid 14181711)
67. Guarda LG, Silva EG, Ordóñez NG, et al. Factor VIII in Kaposi's sarcoma. Am J Clin Pathol. 1981;76:197-200. (Pubitemid 11044423)
68. Leader M, Collins M, Patel J, et al. Staining for factor VIII related antigen and Ulex europaeus agglutinin I (UEA-I) in 230 tumours. An assessment of their specificity for angiosarcoma and Kaposi's sarcoma. Histopathology. 1986;10:1153-1162. (Pubitemid 17205213)
69. Maglott DR, Feldblyum TV, Durkin AS, et al. Radiation hybrid mapping of SNAP, PCSK2, and THBD (human chromosome 20p). Mamm Genome. 1996;7:400-401. (Pubitemid 126426691)
70. Weiler H, Isermann BH. Thrombomodulin. J Thromb Haemost. 2003;1:1515-1524.
71. Dittman WA, Majerus PW. Structure and function of thrombomodulin: a natural anticoagulant. Blood. 1990;75:329-336. (Pubitemid 20035260)
72. Maruyama I, Bell CE, Majerus PW. Thrombomodulin is found on endothelium of arteries, veins, capillaries, and lymphatics, and on syncytiotrophoblasts of human placenta. J Cell Biol. 1985;101:363-371. (Pubitemid 15239110)
73. Collins CL, Ordóñez NG, Schaefer R, et al. Thrombomodulin expression in malignant pleural mesothelioma and pulmonary adenocarcinoma. Am J Pathol. 1992;141:827-833.
74. Jackson DE, Mitchell CA, Bird P, et al. Immunohistochemical localization of thrombomodulin in normal human skin and skin tumours. J Pathol. 1995;175:421-432.
75. Ordóñez NG. Thrombomodulin expression in transitional cell carcinoma. Am J Clin Pathol. 1998;110:385-390. (Pubitemid 28406998)
76. Yonezawa S, Maruyama I, Sakae K, et al. Thrombomodulin as a marker for vascular tumors: comparative study with factor VIII and Ulex europaeus I lectin. Am J Clin Pathol. 1987;88:405-411. (Pubitemid 17142206)
77. Appleton MAC, Attanoos RL, Jasani B. Thrombomodulin as a marker of vascular and lymphatic tumours. Histopathology. 1996;29:153-157. (Pubitemid 26264440)
78. Ordóñez NG. Value of thrombomodulin immunostaining in the diagnosis of mesothelioma. Histopathology. 1997;31:25-30. (Pubitemid 27314502)
79. Ordóñez NG. The immunohistochemical diagnosis of mesothelioma: a comparative study of epithelioid mesothelioma and lung adenocarcinoma. Am JSurgPathol. 2003;27:1031-1051. (Pubitemid 36909525)
80. Ordóñez NG. Value of thrombomodulin immunostaining in the diagnosis of transitional cell carcinoma: a comparative study with carcinoembryonic antigen. Histopathology. 1997;31:517-524. (Pubitemid 28008014)
81. Ascoli V, Scalzo CC, Taccogna S, et al. The diagnostic value of thrombomodulin immunolocalization in serous effusions. Arch Pathol Lab Med. 1995;119:1136-1140. (Pubitemid 26068766)
82. Wasylyk B, Hahn SL, Giovane A. The Ets family of transcription factors. Eur J Biochem. 1993;211:7-18. (Pubitemid 23039491)
83. Oikawa T, Yamada T. Molecular biology of the Ets family of transcription factors. Gene. 2003;303:11-34. (Pubitemid 36151767)
84. Truong AH, Ben-David Y. The role of Fli-1 in normal cell function and malignant transformation. Oncogene. 2000;19:6482-6489. (Pubitemid 32108438)
85. Mhawech-Fauceglia P, Herrmann F, Penetrante R, et al. Diagnostic utility of FLI-1 monoclonal antibody and dualcolour, break-apart probe fluorescence in situ (FISH) analysis in Ewing's sarcoma/primitive neuroectodermal tumour (EWS/PNET). A comparative study with CD99 and FLI-1 polyclonal antibodies. Histopathology. 2006;49:569-575. (Pubitemid 44924288)
86. Folpe AL, Chand EM, Goldblum JR, et al. Expression of FLi-1, a nuclear transcription factor, distinguishes vascular neoplasms from potential mimics. Am J Surg Pathol. 2001;25:1061-1066. (Pubitemid 32685904)
87. Rossi S, Orvieto E, Furlanetto A, et al. Utility of the immunohistochemical detection of FLI-1 expression in round cell and vascular neoplasm using a monoclonal antibody. Mod Pathol. 2004;17:547-552. (Pubitemid 38868421)
88. Mhawech-Fauceglia P, Herrmann FR, Bshara W, et al. Friend leukaemia integration-1 expression in malignant and benign tumours: a multiple tumour tissue microarray analysis using polyclonal antibody. J Clin Pathol. 2007;60:694-700. (Pubitemid 46975228)
89. Billings SD, Folpe AL, Weiss SW. Epithelioid sarcoma-like hemangioendothelioma. Am J Surg Pathol. 2003;27:48-57. (Pubitemid 36014898)
90. Bahrami A, Allen TC, Cagle PT. Pulmonary epithelioid hemangioendothelioma mimicking mesothelioma. Pathol Int. 2008;58:730-734.
91. Jimenez RE, Folpe AL, Lapham RL, et al. Primary Ewing's sarcoma/primitive neuroectodermal tumor of the kidney: a clinicopathologic and immunohistochemical analysis of 11 cases. Am J Surg Pathol. 2002;26:320-327. (Pubitemid 34184455)
92. Ge Y, Ro JY, Kim D, et al. Clinicopathologic and immunohistochemical characteristics of adult primary cardiac angiosarcomas: analysis of 10 cases. Ann Diagn Pathol. 2011;15:262-267.
93. Kuroda N, Hamaguchi N, Inoue K, et al. Application of immunocytochemistry to the diagnosis of primary epithelioid angiosarcoma of the lung. Med Mol Morphol. 2009;42:250-253.
94. Nunes Rosado FG, Itani DM, Coffin CM, et al. Utility of immunohistochemical staining with FLI1, D2-40, CD31, and CD34 in the diagnosis of acquired immunodeficiency syndrome-related and non-acquired immunodeficiency syndromerelated Kaposi sarcoma. Arch Pathol Lab Med. 2012;136:301-304.
95. Llombart B, Monteagudo C, López-Guerrero JA, et al. Clinicopathological and immunohistochemical analysis of 20 cases of Merkel cell carcinoma in search of prognostic markers. Histopathology. 2005;46:622-634. (Pubitemid 40834821)
96. Folpe AL, Hill CE, Parham DM, et al. Immunohistochemical detection of FLI-1 protein expression: a study of 132 round cell tumors with emphasis on CD99-positive mimics of Ewing's sarcoma/primitive neuroectodermal tumor. Am J Surg Pathol. 2000;24:1657-1662.
97. Llombart-Bosch A, Navarro S. Immunohistochemical detection of EWS and FLI-1 proteins in Ewing sarcoma and primitive neuroectodermal tumors: comparative analysis with CD99 (MIC-2) expression. Appl Immunohistochem Mol Morphol. 2001;9:255-260. (Pubitemid 32783049)
98. Graves BJ, Petersen JM. Specificity within the ets family of transcription factors. Adv Cancer Res. 1998;75:1-55. (Pubitemid 28429032)
99. Sharrocks AD, Brown AL, Ling Y, et al. The ETS-domain transcription factor family. Int J Biochem Cell Biol. 1997;29:1371-1387. (Pubitemid 28153488)
100. Birdsey GM, Dryden NH, Amsellem V, et al. Transcription factor Erg regulates angiogenesis and endothelial apoptosis through VE-cadherin. Blood. 2008;111:3498-3506.
101. Tomlins SA, Rhodes DR, Perner S, et al. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science. 2005;310:644-648. (Pubitemid 41528150)
102. Kumar-Sinha C, Tomlins SA, Chinnaiyan AM. Recurrent gene fusions in prostate cancer. Nat Rev Cancer. 2008;8:497-511.
103. Clark JP, Cooper CS. ETS gene fusions in prostate cancer. Nat Rev Urol. 2009;6:429-439.
104. Miettinen M, Wang ZF, Paetau A, et al. ERG transcription factor as an immunohistochemical marker for vascular endothelial tumors and prostatic carcinoma. Am J Surg Pathol. 2011;35:432-441.
105. McKenney JK, Weiss SW, Folpe AL. CD31 expression in intratumoral macrophages: a potential diagnostic pitfall. Am J Surg Pathol. 2001;25:1167-1173. (Pubitemid 32777716)
106. Mohamed AA, Tan SH, Mikhalkevich N, et al. Ets family protein, erg expression in developing and adult mouse tissues by a highly specific monoclonal antibody. J Cancer. 2010;1:197-208.
107. Park K, Tomlins SA, Mudaliar KM, et al. Antibody-based detection of ERG rearrangement-positive prostate cancer. Neoplasia. 2010;12:590-598.
108. Natkunam Y, Zhao S, Mason DY, et al. The oncoprotein LMO2 is expressed in normal germinal-center B cells and in human B-cell lymphomas. Blood. 2007;109:1636-1642. (Pubitemid 46239598)
109. Gerhardt H, Golding M, Fruttiger M, et al. VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. J Cell Biol. 2003;161:1163-1177. (Pubitemid 36870177)
110. Shibuya M. Vascular endothelial growth factor (VEGF) Receptor2: its biological functions, major signaling pathway, and specific ligand VEGF-E. Endothelium. 2006;13:63-69. (Pubitemid 44173108)
111. Miettinen M, Rikala MS, Rys J, et al. Vascular endothelial growth factor receptor 2 as a marker for malignant vascular tumors and mesothelioma: an immunohistochemical study of 262 vascular endothelial and 1640 nonvascular tumors. Am J Surg Pathol. 2012;36:629-639.
112. Jakab C, Halász J, Kiss A, et al. Claudin-5 protein is a new differential marker for histopathological differential diagnosis of canine hemangiosarcoma. Histol Histopathol. 2009;24:801-813.
113. Miettinen M, Sarlomo-Rikala M, Wang ZF. Claudin-5 as an immunohistochemical marker for angiosarcoma and hemangioendotheliomas. Am J Surg Pathol. 2011;35:1848-1856.
114. Shon W, Popp LA, Folpe AL. Claudin-5: a novel, highly sensitive and specific endothelial marker [abstract]. Mod Pathol. 2011;24(suppl 1):21A.
115. Wetterwald A, Hoffstetter W, Cecchini MG, et al. Characterization and cloning of the E11 antigen, a marker expressed by rat osteoblasts and osteocytes. Bone. 1996;18:125-132. (Pubitemid 26092592)
116. Marks A, Sutherland DR, Bailey D, et al. Characterization and distribution of an oncofetal antigen (M2A antigen) expressed on testicular germ cell tumours. Br J Cancer. 1999;80:569-578. (Pubitemid 29213215)
117. Ordóñez NG. Podoplanin: a novel diagnostic immunohistochemical marker. Adv Anat Pathol. 2006;13:83-88. (Pubitemid 44350516)
118. Breiteneder-Geleff S, Matsui K, Soleiman A, et al. Podoplanin, novel 43-kd membrane protein of glomerular epithelial cells, is down-regulated in puromycin nephrosis. Am J Pathol. 1997;151:1141-1152. (Pubitemid 27424324)
119. Hong YK, Harvey N, Noh YH, et al. Prox1 is a master control gene in the program specifying lymphatic endothelial cell fate. Dev Dyn. 2002;225:351-357. (Pubitemid 35265813)
120. Schacht V, Ramirez MI, Hong YK, et al. T1alpha/podoplanin deficiency disrupts normal lymphatic vasculature formation and causes lymphedema. EMBO J. 2003;22:3546-3556. (Pubitemid 36898332)
121. Schacht V, Dadras SS, Johnson LA, et al. Up-regulation of the lymphatic marker podoplanin, a mucin-type transmembrane glycoprotein, in human squamous cell carcinomas and germ cell tumors. Am J Pathol. 2005;166:913-921. (Pubitemid 40315647)
122. Sugimoto Y, Watanabe M, Oh-hara T, et al. Suppression of experimental lung colonization of a metastatic variant of murine colon adenocarcinoma 26 by a monoclonal antibody 8F11 inhibiting tumor cell-induced platelet aggregation. Cancer Res. 1991;51:921-925.
123. Watanabe M, Okochi E, Sugimoto Y, et al. Identification of a platelet-aggregating factor of murine colon adenocarcinoma 26: Mr 44, 000 membrane protein as determined by monoclonal antibodies. Cancer Res. 1988;48:6411-6416.
124. Sinzelle E, Duong Van Huyen JP, Breiteneder-Geleff S, et al. Intrapericardial lymphangioma with podoplanin immunohistochemical characterization of lymphatic endothelial cells. Histopathology. 2000;37:93-94. (Pubitemid 30496746)
125. Arai E, Kuramochi A, Tsuchida T, et al. Usefulness of D2-40 immunohistochemistry for differentiation between kaposiform hemangioendothelioma and tufted angioma. J Cutan Pathol. 2006;33:492-497. (Pubitemid 44049886)
126. Hansen T, Katenkamp K, Bittinger F, et al. D2-40 labeling in lymphangiomyoma/lymphangiomyomatosis of the soft tissue: further evidence of lymphangiogenic tumor histogenesis. Virchows Arch. 2007;450:449-453. (Pubitemid 46466390)
127. Franke FE, Steger K, Marks A, et al. Hobnail hemangiomas (targetoid hemosiderotic hemangiomas) are true lymphangiomas. J Cutan Pathol. 2004;31:362-367. (Pubitemid 38530120)
128. Pyakurel P, Pak F, Mwakigonja AR, et al. Lymphatic and vascular origin of Kaposi's sarcoma spindle cells during tumor development. Int J Cancer. 2006;119:1262-1267. (Pubitemid 44258798)
129. Ordóñez NG. D2-40 and podoplanin are highly specific and sensitive immunohistochemical markers of epithelioid malignant mesothelioma. Hum Pathol. 2005;36:372-380. (Pubitemid 40591807)
130. Tokuyama W, Mikami T, Masuzawa M, et al. Autocrine and paracrine roles of VEGF/VEGFR-2 and VEGF-C/VEGFR-3 signaling in angiosarcomas of the scalp and face. Hum Pathol. 2010;41:407-414.
131. Requena L, Santonja C, Stutz N, et al. Pseudolymphomatous cutaneous angiosarcoma: a rare variant of cutaneous angiosarcoma readily mistaken for cutaneous lymphoma. Am J Dermatopathol. 2007;29:342-350. (Pubitemid 47220484)
132. Naqvi J, Ordóñez NG, Luna MA, et al. Epithelioid hemangioendothelioma of the head and neck: role of podoplanin in the differential diagnosis. Head Neck Pathol. 2008;2:25-30.
133. Parsons A, Sheehan DJ, Sangueza OP. Retiform hemangioendotheliomas usually do not express D2-40 and VEGFR3. Am J Dermatopathol. 2008;30:31-33. (Pubitemid 351161627)
134. Kato Y, Kaneko MK, Kuno A, et al. Inhibition of tumor cellinduced platelet aggregation using a novel anti-podoplanin antibody reacting with its platelet-aggregation-stimulating domain. Biochem Biophys Res Commun. 2006;349:1301-1307. (Pubitemid 44416399)
135. Ishizawa K, Komori T, Shimada S, et al. Podoplanin is a potential marker for the diagnosis of ependymoma: a comparative study with epithelial membrane antigen (EMA). Clin Neuropathol. 2009;28:373-378.
136. Lavado A, Oliver G. Prox1 expression patterns in the developing and adult murine brain. Dev Dyn. 2007;236:518-524. (Pubitemid 46233295)
137. Risebro CA, Searles RG, Melville AA, et al. Prox1 maintains muscle structure and growth in the developing heart. Development. 2009;136:495-505.
138. Dudas J, Papoutsi M, Hecht M, et al. The homeobox transcription factor Prox1 is highly conserved in embryonic hepatoblasts and in adult and transformed hepatocytes, but is absent from bile duct epithelium. Anat Embryol (Berl). 2004;208:359-366. (Pubitemid 39179579)
139. Dudas J, Elmaouhoub A, Mansuroglu T, et al. Prosperorelated homeobox 1 (Prox1) is a stable hepatocyte marker during liver development, injury and regeneration, and is absent from "oval cells". Histochem Cell Biol. 2006;126:549-562. (Pubitemid 44484900)
140. Sosa-Pineda B, Wigle JT, Oliver G. Hepatocyte migration during liver development requires Prox1. Nat Genet. 2000;25:254-255. (Pubitemid 30437306)
141. Burke Z, Oliver G. Prox1 is an early specific marker for the developing liver and pancreas in the mammalian foregut endoderm. Mech Dev. 2002;118:147-155. (Pubitemid 35292129)
142. Wigle JT, Chowdhury K, Gruss P, et al. Prox1 function is crucial for mouse lens-fibre elongation. Nat Genet. 1999;21:318-322. (Pubitemid 29124943)
143. Wigle JT, Oliver G. Prox1 function is required for the development of the murine lymphatic system. Cell. 1999;98:769-778. (Pubitemid 29446894)
144. Miettinen M, Wang ZF. Prox1 transcription factor as a marker for vascular tumors-evaluation of 314 vascular endothelial and 1086 nonvascular tumors. Am J Surg Pathol. 2012;36:351-359.
145. Stacker SA, Achen MG, Jussila L, et al. Lymphangiogenesis and cancer metastasis. Nat Rev Cancer. 2002;2:573-583. (Pubitemid 37328924)
146. Dadras SS, North PE, Bertoncini J, et al. Infantile hemangiomas are arrested in an early developmental vascular differentiation state. Mod Pathol. 2004;17:1068-1079. (Pubitemid 39128233)
147. Reis RM, Reis-Filho JS, Longatto Filho A, et al. Differential Prox-1 and CD 31 expression in mucousae, cutaneous and soft tissue vascular lesions and tumors. Pathol Res Pract. 2005;201:771-776. (Pubitemid 43071564)
148. Nguyen VA, Kutzner H, Fürhapter C, et al. Infantile hemangioma is a proliferation of LYVE-1-negative blood endothelial cells without lymphatic competence. Mod Pathol. 2006;19:291-298. (Pubitemid 43117615)
149. Ji RC, Eshita Y, Kato S. Investigation of intratumoural and peritumoural lymphatics expressed by podoplanin and LYVE-1 in the hybridoma-induced tumours. Int J Exp Pathol. 2007;88:257-270. (Pubitemid 47256302)
150. Lee JY, Spicer AP. Hyaluronan: a multifunctional, megaDalton, stealth molecule. Curr Opin Cell Biol. 2000;12:581-586.
151. Kohda D, Morton CJ, Parkar AA, et al. Solution structure of the link module: a hyaluronan-binding domain involved in extracellular matrix stability and cell migration. Cell. 1996;86:767-775. (Pubitemid 26303445)
152. Mouta Carreira C, Nasser SM, di Tomaso E, et al. LYVE-1 is not restricted to the lymph vessels: Expression in normal liver blood sinusoids and down-regulation in human liver cancer and cirrhosis. Cancer Res. 2001;61:8079-8084. (Pubitemid 33091593)
153. Jackson DG. The lymphatics revisited: new perspectives from the hyaluronan receptor LYVE-1. Trends Cardiovasc Med. 2003;13:1-7. (Pubitemid 36120543)
154. Schledzewski K, Falkowski M, Moldenhauer G, et al. Lymphatic endothelium-specific hyaluronan receptor LYVE-1 is expressed by stabilin-1 +, F4/80 +, CD11b + macrophages in malignant tumours and wound healing tissue in vivo and in bone marrow cultures in vitro: implications for the assessment of lymphangiogenesis. J Pathol. 2006;209:67-77.
155. Arimoto J, Ikura Y, Suekane T, et al. Expression of LYVE-1 in sinusoidal endothelium is reduced in chronically inflamed human livers. J Gastroenterol. 2010;45:317-325.
156. North PE, Kahn T, Cordisco MR, et al. Multifocal lymphangioendotheliomatosis with thrombocytopenia: a newly recognized clinicopathological entity. Arch Dermatol. 2004;140:599-606. (Pubitemid 38668968)
157. Tomita T. Lymphatic vessel endothelial hyaluronan receptor 1 immunocytochemical staining for pancreatic islets and pancreatic endocrine tumors. Pancreas. 2007;35:e18-e22. (Pubitemid 350307392)
158. Tomita T. LYVE-1 immunocytochemical staining for gastrointestinal carcinoids. Pathology. 2009;41:248-253.
159. Kaipainen A, Korhonen J, Mustonen T, et al. Expression of the fms-like tyrosine kinase 4 gene becomes restricted to lymphatic endothelium during development. Proc Natl Acad Sci USA. 1995;92:3566-3570.
160. Galland F, Karamysheva A, Pebusque MJ, et al. The FLT4 gene encodes a transmembrane tyrosine kinase related to the vascular endothelial growth factor receptor. Oncogene. 1993;8:1233-1240. (Pubitemid 23129845)
161. Pajusola K, Aprelikova O, Armstrong E, et al. Two human FLT4 receptor tyrosine kinase isoforms with distinct carboxy terminal tails are produced by alternative processing of primary transcripts. Oncogene. 1993;8:2931-2937. (Pubitemid 23312896)
162. Witte D, Thomas A, Ali N, et al. Expression of the vascular endothelial growth factor receptor-3 (VEGFR-3) and its ligand VEGF-C in human colorectal adenocarcinoma. Anticancer Res. 2002;22:1463-1466. (Pubitemid 34839151)
163. Hansel DE, Rahman A, Hermans J, et al. Liver metastases arising from well-differentiated pancreatic endocrine neoplasms demonstrate increased VEGF-C expression. Mod Pathol. 2003;16:652-659. (Pubitemid 36871497)
164. Li R, Younes M, Wheeler TM, et al. Expression of vascular endothelial growth factor receptor-3 (VEGFR-3) in human prostate. Prostate. 2004;58:193-199. (Pubitemid 38160907)
165. Filho AL, Martins A, Costa SM, et al. VEGFR-3 expression in breast cancer tissue is not restricted to lymphatic vessels. Pathol Res Pract. 2005;201:93-99. (Pubitemid 40443822)
166. Jüsttner S, Wissmann C, Jöns T, et al. Vascular endothelial growth factor-D and its receptor VEGFR-3: two novel independent prognostic markers in gastric adenocarcinoma. J Clin Oncol. 2006;24:228-240. (Pubitemid 46622052)
167. Filho AL, Baltazar F, Bedrossian C, et al. Immunohistochemical expression and distribution of VEGFR-3 in malignant mesothelioma. Diagn Cytopathol. 2007;35:786-791. (Pubitemid 350250764)
168. Partanen TA, Alitalo K, Miettinen M. Lack of lymphatic vascular specificity of vascular endothelial growth factor receptor 3 in 185 vascular tumors. Cancer. 1999;86:2406-2412. (Pubitemid 30010384)
169. Saito M, Gunji Y, Kashii Y, et al. Refractory kaposiform hemangioendothelioma that expressed vascular endothelial growth factor receptor (VEGFR)-2 and VEGFR-3: a case report. J Pediatr Hematol Oncol. 2009;31:194-197.
170. Itakura E, Yamamoto H, Oda Y, et al. VEGF-C and VEGFR3 in a series of lymphangiomas: is superficial lymphangioma a true lymphangioma? Virchows Arch. 2009;454:317-325.
171. Schlingemann RO, Dingjan GM, Emeis JJ, et al. Monoclonal antibody PAL-E specific for endothelium. Lab Invest. 1985;52:71-76. (Pubitemid 15157614)
172. Keuschnigg J, Henttinen T, Auvinen K, et al. The prototype endothelial marker PAL-E is a leukocyte trafficking molecule. Blood. 2009;114:478-484.
173. Keuschnigg J, Tvorogov D, Elima K, et al. PV-1 is recognized by the PAL-E antibody and forms complexes with NRP-1. Blood. 2012;120:232-235.
174. Stan RV, Ghitescu L, Jacobson BS, et al. Isolation, cloning, and localization of rat PV-1, a novel endothelial caveolar protein. J Cell Biol. 1999;145:1189-1198. (Pubitemid 29293631)
175. Nadimi H, Saatee S, Armin A, et al. Expression of endothelial cell markers PAL-E and EN-4 and Ia-antigens in Kaposi's sarcoma. J Oral Pathol. 1988;17:416-420.