Lee, M.S. ; Lupp, A.* ; Mendoza, N.M.* ; Martin, N.M.* ; Beschorner, R.* ; Honegger, J.* ; Schlegel, J.* ; Shively, T.* ; Pulz, E. ; Schulz, S.* ; Roncaroli, F.* ; Pellegata, N.S.
SSTR3 is a putative target for the medical treatment of gonadotroph adenomas of the pituitary.
Endocr. Relat. Cancer 22, 111-119 (2015)
Gonadotroph pituitary adenomas (GPAs) often present as invasive macroadenomas not amenable to complete surgical resection. Radiotherapy is the only post-operative option for patients with large invasive or recurrent lesions. No medical treatment is available for these patients. The somatostatin analogues (SSAs) octreotide and lanreotide that preferentially target somatostatin receptor type 2 (SSTR2) have little effect on GPAs. It is widely accepted that the expression of specific SSTR subtypes determines the response to SSAs. Given that previous studies on mRNA and protein expression of SSTRs in GPAs generated conflicting results, we investigated the expression of SSTR2, SSTR3 and SSTR5 (the main targets of available SSAs) in a clinically and pathologically well characterized cohort of 108 patients with GPAs. A total of 118 samples were examined by immunohistochemistry using validated and specific monoclonal antibodies. Matched primary and recurrent tissues were available for 10 patients. The results obtained were validated in an independent cohort of 27 GPAs. We observed that SSTR3 was significantly more abundant than SSTR2 (P<0.0001) in GPAs, while full-length SSTR5 was only expressed in few tumors. SSTR3 expression was similar in primary and recurrent adenomas, was high in potentially aggressive lesions and did not significantly change in adenomas that recurred after irradiation. In conclusion, low expression of SSTR2 may account for the limited response of GPAs to octreotide and lanreotide. Given the potent anti-proliferative, pro-apoptotic and anti-angiogenic activities of SSTR3, targeting this receptor with a multireceptor ligand SSA such as pasireotide may be indicated for potentially aggressive GPAs.
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Times Cited
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
Aggressive Adenoma ; Gonadotroph Adenoma ; Pasireotide ; Somatostatin Receptors; Somatostatin Receptor Subtypes; Cushings-disease; Follow-up; In-vivo; Pasireotide; Expression; Tumors; Growth; Mechanisms; Efficacy
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2015
Prepublished im Jahr
2014
HGF-Berichtsjahr
2014
ISSN (print) / ISBN
1351-0088
e-ISSN
1479-6821
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 22,
Heft: 1,
Seiten: 111-119
Artikelnummer: ,
Supplement: ,
Reihe
Verlag
BioScientifica
Verlagsort
Bristol
Tag d. mündl. Prüfung
0000-00-00
Betreuer
Gutachter
Prüfer
Topic
Hochschule
Hochschulort
Fakultät
Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
Anmeldeland
Priorität
Begutachtungsstatus
Peer reviewed
POF Topic(s)
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Forschungsfeld(er)
Enabling and Novel Technologies
PSP-Element(e)
G-500300-001
Förderungen
Copyright
Erfassungsdatum
2014-12-31