- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York, India
Mahlon D. Johnson
Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York, India
DOI:10.4103/2152-7806.196367Copyright: © 2016 Surgical Neurology International This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
How to cite this article: Mahlon D. Johnson. Do mesothelin/MUC16 interactions facilitate adenocarcinoma metastases to intracranial meningiomas?. 21-Dec-2016;7:
How to cite this URL: Mahlon D. Johnson. Do mesothelin/MUC16 interactions facilitate adenocarcinoma metastases to intracranial meningiomas?. 21-Dec-2016;7:. Available from: http://surgicalneurologyint.com/surgicalint_articles/do-mesothelinmuc16-interactions-facilitate-adenocarcinoma-metastases-to-intracranial-meningiomas/
Background:Meningiomas have been shown to express mesothelin, a high affinity binding site for MUC16, a transmembrane protein on adenocarcinoma cells. The mechanisms underlying adenocarcinoma metastases to meningiomas may provide insight into tumor-to-tumor metastases and adenocarcinoma metastases to leptomeningeal cells.
Methods:Two meningiomas containing metastases from adenocarcinomas were identified and evaluated immunohistochemically for the expression and localization of mesothelin and MUC16.
Results:Both meningiomas show extensive mesothelin immunoreactivity, and the adenocarcinomas metastatic to the meningiomas show mesothelin and MUC16 immunoreactivity at the interface with meningioma.
Conclusions:Interactions between MUC16 and/or mesothelin on the cell membrane of adenocarcinoma cells with mesothelin on meningioma cells may facilitate adenocarcinoma metastases to meningiomas and possibly the leptomeninges.
Keywords: Meningiona, mesothelin, metastasis, MUC16, tumor-to-tumor
Adenocarcinomas are one group of carcinomas known to metastasize to the leptomeninges.[
Transmembrane mucins such as MUC1 and MUC16 are thought to facilitate the metastases of many carcinomas, including pulmonary adenocarcinomas.[
Mesothelin is a 40kDa glycosyl-phosphatidylinositol-anchored cell surface protein that has been identified in low levels in mesothelial cells of the pleura, pericardium, and peritoneum.[
Recently, it has been shown that mesothelin binds MUC16, a type I transmembrane protein that belongs to the mucin family of glycoproteins. It is also called CA125.[
Two meningiomas with intratumoral adenocarcinoma were identified in the University of Rochester archives and consultative material after obtaining Institutional Review Board approval. The first was from a 74-year-old male with a right frontal transitional meningioma. He had a known lung mass. The second patient was a 66-year-old female with a left sphenoid wing meningioma and an adenocarcinoma identified 2 years earlier.
Each case was analyzed with a monoclonal antibody to human mesothelin.[
Patient 1. The sections revealed a transitional, meningioma containing a relatively circumscribed, poorly differentiated adenocarcinoma with clear cell features and necrosis. The metastasis exhibited vimentin, cytokeratin 7, TTF-1, and AE1/AE3, however, no cytokeratin 20 or S-100 immunoreactivity. The adenocarcinoma had clear periodic acid schiff (PAS) and dPAS negative cytoplasm, large pleomorphic nuclei with prominent nucleoli, and focal glandular formation and necrosis. Ki-67 labeling was brisk in the metastasis and approximately 6% in the meningioma. The meningioma had numerous whorls and rare mitoses, but no loss of lobularity, with only modest cellularity and no definite small cell component. The PAS/PAS-D stain revealed no clear cell component.
Patient 2. The meningioma was transitional with atypical features, including hypercellularity, focal loss of lobular pattern, small cell change, and focal necrosis. The meningioma showed extensive epithelial membrane antigen (EMA) but no CAM 5.2, cytokeratin 7, TTF-1, napsyn, or PAS staining. The metastatic adenocarcinoma shows gland formation. The epithelioid cells had prominent nucleoli, high mitotic activity, and necrosis and Kreyberg staining. The carcinoma cells showed EMA, Cam 5.2, cytokeratin 7, napsyn, TTF-1, and Ki-67 labeling of 60%.
Mesothelin immunoreactivity was detected in both meningiomas and was extensive [Figure
Mesothelin and MUC16 expression in meningiomas with adenocarcinoma metastasis in patient 1. Meningioma with mesothelin immunoreactivity (a) but no MUC16 (b). Metastatic adenocarcinoma to meningioma showing mesothelin (c) and MUC16 (d) Hematoxylin counterstain and diaminobenzidine chromagen (Original magnification, ×400)
Mesothelin and MUC16 expression in meningiomas with adenocarcinoma metastasis in patient 2. Meningioma with mesothelin immunoreactivity in meningioma (a) and in adenocarcinoma metastatic to meningioma (c). Lack of MUC 16 in meningioma (b) but extensive immunoreactivity in adenocarcinoma (d) Hematoxylin counterstain and diaminobenzidine chromagen (Original magnification, ×400)
Muc16 immunoreactivity was not detected in either meningioma [Figure
Previously, we have demonstrated mesothelin expression in the majority of meningioma and 30% of human leptomeninges tested.[
In contrast, meningiomas show widespread mesothelin expression and may have more favorable binding sites for MUC16-expressing carcinomas. Consistent with this is our finding of widespread mesothelin in both meningiomas as well as MUC16 in both carcinomas. Thus, these interactions may represent another mechanism by which tumors metastasize to remote tissues (and tumors).[
Mesothelin may also facilitate metastases by other mechanisms. Recent studies have shown that mesothelin induces expression of metaloproteinase MMP9, which has been implicated in tumor invasion.[
Targeting mesothelin with an anti-mesothlin immunotoxin SS1P binding has been shown to cause regression of mesothelin-expressing tumors in athymic mice. It also has exhibited tumoricidal effects on mesotheliomas and ovarian carcinomas.[
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