The Role of Mediators of Cell Invasiveness, Motility, and Migration in the Pathogenesis of Silent Corticotroph Adenomas

Mete O., Hayhurst C., Alahmadi H., Monsalves E., Gucer H., Gentili F., ...Daha Fazla

ENDOCRINE PATHOLOGY, cilt.24, sa.4, ss.191-198, 2013 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 24 Sayı: 4
  • Basım Tarihi: 2013
  • Doi Numarası: 10.1007/s12022-013-9270-y
  • Dergi Adı: ENDOCRINE PATHOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.191-198
  • Anahtar Kelimeler: Silent Corticotroph Adenoma, Non-Functioning Pituitary Adenoma, Osteopontin, FGFR4, MMP-1, Integrin, NONFUNCTIONING PITUITARY-ADENOMAS, GROWTH-FACTOR RECEPTOR-4, RAT ANTERIOR-PITUITARY, EXTRACELLULAR-MATRIX COMPONENTS, CANCER INVASION, IN-VITRO, OSTEOPONTIN, EXPRESSION, ADHESION, ISOFORM
  • Recep Tayyip Erdoğan Üniversitesi Adresli: Evet

Özet

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 beta 1-integrin, osteopontin, and matrix metalloproteinase-1 (MMP-1) as cytoplasmic, membranous, or mixed cytoplasmic-membranous staining to achieve scores of 1-4. Staining for beta 1-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.