naa a22 4500 510773532 CHVBK 20180411083222.0 cr unu---uuuuu 180411e20131201xx s 000 0 eng 10.1007/s12022-013-9270-y doi (NATIONALLICENCE)springer-10.1007/s12022-013-9270-y The Role of Mediators of Cell Invasiveness, Motility, and Migration in the Pathogenesis of Silent Corticotroph Adenomas [Elektronische Daten] [Ozgur Mete, Caroline Hayhurst, Hussein Alahmadi, Eric Monsalves, Hasan Gucer, Fred Gentili, Shereen Ezzat, Sylvia Asa, Gelareh Zadeh] Silent corticotroph adenomas (SCAs) represent a distinct subset of clinically non-functioning pituitary adenomas. There are two variants of SCA; type I are densely granulated basophilic tumors and type II are sparsely granulated and chromophobic tumors. SCAs are known to be aggressive than the more common non-functioning gonadotroph adenomas (NFGAs). Cell-matrix interactions play an important role in the pathogenesis of pituitary adenomas. In this study, we compared 19 SCAs and 50 NFGAs with known fibroblast growth factor receptor-4 (FGFR4) status using semi-quantitative immunohistochemistry to localize β1-integrin, osteopontin, and matrix metalloproteinase-1 (MMP-1) as cytoplasmic, membranous, or mixed cytoplasmic-membranous staining to achieve scores of 1-4. Staining for β1-integrin was significantly higher in SCAs (100%, score 3.3) than in NFGAs (96%; score 2.6) (p = 0.0482); there was no statistical difference within subgroups of SCA (type II score 3.4; type I score 2.8) (p = 0.2663). Osteopontin immunoreactivity was also higher in SCAs (100%, score 3.7) than in NFGAs (42%, score 0.8) (p = 0.0001); there was no statistical difference within subgroups of SCA (type II score 3.6; type I score 3.9) (p = 0.2787). In contrast, MMP-1 immunoreactivity was lower in SCAs (89%; score 2.5) than in NFGAs (98%; score 3.6) (p = 0.0005); there was no statistical difference within subgroups of SCA (type II score 2.7; type I score 2.0) (p = 0.30704). The MMP-1 results correlated with FGFR4 expression (NFGA 96%, type II SCA 71%, type I SCA 40%). Our data indicate that the biological aggressivity of SCAs compared with NFGA may be due to high osteopontin expression; in contrast, high MMP-1 is characteristic of NFGAs that also express more FGFR4. Further investigations are warranted to clarify the underlying regulatory mechanisms of these markers. The high osteopontin or FGFR4/MMP-1 expression levels in SCAs and NFGAs, respectively, indicate the potential for therapeutic strategies targeting osteopontin or FGFR4/MMP-1 for inoperable tumors of these types. Springer Science+Business Media New York, 2013 Silent Corticotroph Adenoma nationallicence Non-Functioning Pituitary Adenoma nationallicence Osteopontin nationallicence FGFR4 nationallicence MMP-1 nationallicence Integrin nationallicence Mete Ozgur Department of Pathology, University Health Network, 200 Elizabeth Street, 11th floor, M5G 2C4, Toronto, ON, Canada aut Hayhurst Caroline Department of Neurosurgery, University Health Network, Toronto, ON, Canada aut Alahmadi Hussein Department of Neurosurgery, University Health Network, Toronto, ON, Canada aut Monsalves Eric Department of Neurosurgery, University Health Network, Toronto, ON, Canada aut Gucer Hasan Department of Pathology, University Health Network, 200 Elizabeth Street, 11th floor, M5G 2C4, Toronto, ON, Canada aut Gentili Fred Endocrine Oncology Site Group, Princess Margaret Hospital, Toronto, ON, Canada aut Ezzat Shereen Endocrine Oncology Site Group, Princess Margaret Hospital, Toronto, ON, Canada aut Asa Sylvia Department of Pathology, University Health Network, 200 Elizabeth Street, 11th floor, M5G 2C4, Toronto, ON, Canada aut Zadeh Gelareh Endocrine Oncology Site Group, Princess Margaret Hospital, Toronto, ON, Canada aut Endocrine Pathology Springer US; http://www.springer-ny.com 24/4(2013-12-01), 191-198 1046-3976 24:4<191 2013 24 12022 https://doi.org/10.1007/s12022-013-9270-y text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s12022-013-9270-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Mete Ozgur Department of Pathology, University Health Network, 200 Elizabeth Street, 11th floor, M5G 2C4, Toronto, ON, Canada aut NATIONALLICENCE 700 1- Hayhurst Caroline Department of Neurosurgery, University Health Network, Toronto, ON, Canada aut NATIONALLICENCE 700 1- Alahmadi Hussein Department of Neurosurgery, University Health Network, Toronto, ON, Canada aut NATIONALLICENCE 700 1- Monsalves Eric Department of Neurosurgery, University Health Network, Toronto, ON, Canada aut NATIONALLICENCE 700 1- Gucer Hasan Department of Pathology, University Health Network, 200 Elizabeth Street, 11th floor, M5G 2C4, Toronto, ON, Canada aut NATIONALLICENCE 700 1- Gentili Fred Endocrine Oncology Site Group, Princess Margaret Hospital, Toronto, ON, Canada aut NATIONALLICENCE 700 1- Ezzat Shereen Endocrine Oncology Site Group, Princess Margaret Hospital, Toronto, ON, Canada aut NATIONALLICENCE 700 1- Asa Sylvia Department of Pathology, University Health Network, 200 Elizabeth Street, 11th floor, M5G 2C4, Toronto, ON, Canada aut NATIONALLICENCE 700 1- Zadeh Gelareh Endocrine Oncology Site Group, Princess Margaret Hospital, Toronto, ON, Canada aut NATIONALLICENCE 773 0- Endocrine Pathology Springer US; http://www.springer-ny.com 24/4(2013-12-01), 191-198 1046-3976 24:4<191 2013 24 12022 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer