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

Our plain-English summary of 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, by M. Miettinen, M.S. Rikala, J. Rys, et al (The American Journal of Surgical Pathology, 2012).

The study

• Authors: M. Miettinen, M.S. Rikala, J. Rys, J. Lasota, Z.F. Wang
• Journal: The American Journal of Surgical Pathology
• Published: 2012;36(4):629-39
• Cited by: 85 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Vascular endothelial growth factor receptor 2 (VEGFR2) is a primary responder to vascular endothelial growth factor signal and thereby regulates endothelial migration and proliferation. This receptor is expressed in endothelial cells and in some vascular tumors, but many reports also detail its expression in carcinomas and lymphomas. VEGFR2 is a potential cell-type marker, and data on VEGFR2 expression may also have therapeutic significance in view of recent availability of VEGFR2 inhibitors. In this study, we immunohistochemically examined 262 vascular endothelial and 1640 nonvascular tumors and selected non-neoplastic tissues with a VEGFR2-specific rabbit monoclonal antibody 55B11. In early human embryo, VEFGR2 was expressed in endothelia of developing capillaries and in the thoracic duct, great vessels, hepatic sinusoids, epidermis, and mesothelia. In late first trimester fetus peripheral soft tissues, VEGFR2 was restricted to capillary endothelia, chondrocytes, and superficial portion of the epidermis. In normal adult tissues, it was restricted to endothelia and mesothelia. VEGFR2 was consistently expressed in angiosarcomas, Kaposi sarcomas, and retiform hemangioendotheliomas. It was detected in only half of epithelioid hemangioendotheliomas (15/27), usually focally. VEGFR2 was strongly expressed in most capillary hemangiomas and weakly or focally in cavernous, venous, and spindle cell hemangiomas and in lymphangiomas. Malignant epithelial mesothelioma was found to be a unique epithelial neoplasm with a strong and nearly consistent VEGFR2 expression, including membrane staining (35/38). Approximately 10% of squamous cell carcinomas and 23% of pulmonary adenocarcinomas contained focal positivity. The only nonendothelial mesenchymal tumors found to be VEGFR2 positive were biphasic synovial sarcoma (focal epithelial expression) and chordoma. All melanomas and lymphomas were negative. VEGFR2 is a promising marker for malignant vascular tumors and malignant epithelioid mesothelioma. Expression in biphasic synovial sarcoma epithelium, chordoma, and some carcinomas has to be considered in differential diagnosis. Information on VEGFR2 tissue expression may be useful in development of targeted oncologic therapy through VEGFR2-specific tyrosine kinase inhibitors.

In plain English

In this laboratory study, the authors tested whether a protein, VEGFR2, helps identify certain tumors under the microscope. They stained surgical tissue samples with a VEGFR2-detecting antibody. The samples were 262 vascular endothelial tumors (blood and lymphatic vessel tumors), 793 other soft-tissue, neuroectodermal (including melanoma) and blood-cell tumors, 847 epithelial tumors, and selected normal fetal and adult tissues. The study did not examine asbestos exposure. In normal adult tissue, VEGFR2 was essentially limited to vessel linings (endothelia) and mesothelium. Of 38 epithelial malignant mesotheliomas, 35 (92%) were positive, mostly with staining along cell membranes. All 6 sarcomatoid mesotheliomas and 3 purely solid epithelial mesotheliomas were negative. Focal staining without distinct membrane staining was seen in 12 of 53 lung adenocarcinomas (23%), and focal staining in about 10% of squamous cell carcinomas. Of 89 angiosarcomas, 85 were positive, as were all 30 Kaposi sarcomas. The authors concluded that VEGFR2 is a new supplemental marker for malignant mesothelioma. They added that it is not suitable for detecting sarcomatoid mesothelioma, and that other markers may be needed to separate mesothelioma from angiosarcoma.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory immunohistochemistry (tissue staining) study of tumor and normal tissue samples
• Who was studied: The study covered 262 vascular endothelial tumors, including hemangiomas, lymphangiomas, hemangioendotheliomas, angiosarcomas and Kaposi sarcomas. It also covered 793 nonendothelial mesenchymal, neuroectodermal (including melanomas) and hematopoietic tumors, and 847 epithelial neoplasms (almost all malignant). The epithelial group included 38 epithelial and 6 sarcomatoid malignant mesotheliomas. Selected normal developing and adult tissues were included as well. All came from surgical specimens and were used anonymously. The article does not say where or when the specimens were collected.
• Exposure: Asbestos exposure was not studied. Tissues were stained with a VEGFR2-specific rabbit monoclonal antibody, 55B11. Angiosarcomas were tabulated by subgroup, including 10 radiation-associated cases, all positive.
• Main results:
  • In normal adult tissues, VEGFR2 staining was restricted to endothelia and mesothelia.
  • Epithelial malignant mesothelioma: 35/38 cases (92%) were positive, typically with extensive, mainly membrane staining.
  • Three purely solid epithelial mesotheliomas and all 6 sarcomatoid mesotheliomas were negative.
  • Lung (pulmonary) adenocarcinoma: 12/53 (23%) showed focal cytoplasmic staining without distinct membrane staining. About 10% of squamous cell carcinomas had focal positivity.
  • Testicular embryonal carcinoma: 6/15 contained clusters of positive cells. All seminomas were negative.
  • Angiosarcoma: 85/89 (96%) were positive. Kaposi sarcoma: all 30 cases were positive.
  • Among nonendothelial mesenchymal tumors, positive staining was found only in biphasic synovial sarcoma (7/8) and chordoma (5/10). Melanomas and lymphomas were negative.
• The authors' conclusion: The authors concluded that VEGFR2 is a new supplemental positive marker for malignant mesothelioma, along with calretinin, keratin 5 and WT1. They also concluded that the staining pattern (membrane versus cytoplasmic) can help separate mesothelioma from lung adenocarcinoma.
• Limitations the authors state:
  • The authors stated that because sarcomatoid mesotheliomas lack VEGFR2, the marker is not suitable for detecting them.
  • The authors stated that some solid epithelial mesotheliomas show limited or no VEGFR2 expression.
  • The authors stated that other markers may be needed to tell mesothelioma apart from angiosarcoma, which also strongly expresses VEGFR2.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Carcinoma, Monoclonal Antibody, Sarcoma, Epithelioid, Spindle Cell, Neoplasm, Squamous Cell Carcinoma.

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