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[en] Somatostatin analogs (SSA) with their potent antisecretory and antiproliferative effects are the main medical treatment option for patients with neuroendocrine tumors, such as gastroenteropancreatic and acromegaly-associated growth hormone secreting pituitary tumors. Although a good portion of acromegalic patients gets normalized after SSA treatment, strict hormonal control is not achieved in a sizeable proportion of these patients. The reasons for this incomplete response to SSA treatment are unclear. We have found that the tumor suppressor ZAC1 (LOT1/PLAGL1) is essential for the antiproliferative effect of SSA in pituitary tumor cells. The aim of the present retrospective cohort study was to determine whether ZAC1 immunoreactivity in archival somatotrophinoma tissue derived from 45 patients with acromegaly routinely pretreated with SSA before surgery, was associated with response to SSA (normalization of GH, IGF-I and presence of tumor shrinkage). All tumors displayed ZAC1 immunoreactivity [weak (+; n = 15), moderate (++; n = 16) and strong (+++; n = 14)]. A significant positive correlation was found between strong ZAC1 immunoreactivity and IGF-I normalization and presence of tumor shrinkage after SSA treatment, which was not affected by age at diagnosis, gender or duration of SSA treatment. These in vivo data combined with the antiproliferative properties of ZAC1/Zac1 provide evidence of a mechanistic role for this transcription factor on SSA induced tumor shrinkage and hormone normalization.
Disciplines :
Endocrinology, metabolism & nutrition
Author, co-author :
Theodoropoulou, Marily; Max Planck Institute of Psychiatry > Department of Endocrinology
Tichomirowa, Maria A; Centre Hospitalier Universitaire de Liège - CHU > Department of Endocrinology
Sievers, Caroline; Max Planck Institute of Psychiatry > Department of Endocrinology
Yassouridis, Alexander; Max Planck Institute of Psychiatry > Research Group of Statistics
Arzberger, Thomas; Munchen Ludwig-Maximilians-University > Center for Neuropathology and Prion Research
Hougrand, Olivier ; Centre Hospitalier Universitaire de Liège - CHU > Anatomie pathologique
Deprez, Manuel ; Université de Liège - ULiège > Département des sciences cliniques > Neuropathologie
Daly, Adrian ; Université de Liège - ULiège > Département des sciences cliniques > Endocrinologie
Petrossians, Patrick ; Centre Hospitalier Universitaire de Liège - CHU > Endocrinologie clinique
Pagotto, Uberto; Center for Applied Biomedical Research Orsola-Malpighi General Hospital Italy > Department of Internal Medicine and Gastroenterology
Beckers, Albert ; Université de Liège - ULiège > Département des sciences cliniques > Endocrinologie
Stalla, Gunter K; Max Planck Institute of Psychiatry > Department of Endocrinology
Language :
English
Title :
Tumor ZAC1 expression is associated with the response to somatostatin analog therapy in patients with acromegaly.
Publication date :
November 2009
Journal title :
International Journal of Cancer
ISSN :
0020-7136
eISSN :
1097-0215
Publisher :
Wiley Liss, Inc., New York, United States - New York
Volume :
125
Issue :
9
Pages :
2122-6
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
DFG - Deutsche Forschungsgemeinschaft Novartis Pharma GmbH
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