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Predictive and prognostic significance of tumour subtype,SSTR1-5 and e-cadherin expression in a well-defined cohort of patients with acromegaly
Authors:Jiri Soukup  Helena Hornychova  Monika Manethova  Kvetoslava Michalova  Ludmila Michnova  Lenka Popovska  Veronika Skarkova  Tomas Cesak  David Netuka  Ales Ryska  Jan Cap  Václav Hána  Václav Hána Jr  Michal Kršek  Eva Dvořáková  Michal Krčma  Ivica Lazurova  Věra Olšovská  Karel Starý  Peter Vaňuga  Filip Gabalec
Affiliation:1. The Fingerland Department of Pathology, Faculty of Medicine, University Hospital, Charles University, Hradec Kralove, Czech Republic

Contribution: Data curation (equal), Formal analysis (equal), ​Investigation (lead), Methodology (equal), Visualization (equal), Writing - original draft (equal), Writing - review & editing (equal);2. The Fingerland Department of Pathology, Faculty of Medicine, University Hospital, Charles University, Hradec Kralove, Czech Republic

Contribution: ​Investigation (supporting), Methodology (lead);3. The Fingerland Department of Pathology, Faculty of Medicine, University Hospital, Charles University, Hradec Kralove, Czech Republic

Contribution: Formal analysis (equal), ​Investigation (equal), Methodology (supporting);4. Department of Pathology, Faculty of Medicine, Charles University, Plzen, Czech Republic

Bioptical Laboratory, Ltd., Plzen, Czech Republic

Contribution: Data curation (equal);5. Department of Pathology, Military University Hospital Prague, Prague, Czech Republic

Contribution: Data curation (equal);6. Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Hradec Kralove, Czech Republic

Contribution: Formal analysis (equal), ​Investigation (equal);7. Department of Medical Biology and Genetics, Faculty of Medicine Hradec Kralove, Charles University, Hradec Kralove, Czech Republic

Contribution: Methodology (equal), Validation (equal);8. Department of Neurosurgery, Faculty of Medicine, University Hospital, Charles University, Hradec Kralove, Czech Republic

Contribution: Data curation (equal);9. Department of Neurosurgery and Neurooncology, 1st Medical Faculty, Charles University, Military University Hospital Prague, Prague, Czech Republic

Contribution: Data curation (equal);10. The Fingerland Department of Pathology, Faculty of Medicine, University Hospital, Charles University, Hradec Kralove, Czech Republic

Contribution: Supervision (equal), Writing - review & editing (equal);11. 4th Department of Internal medicine, Faculty of Medicine, University Hospital, Charles University, Hradec Kralove, Czech Republic

Contribution: Supervision (equal), Writing - review & editing (equal);12. 3rd Department of Internal Medicine, 1st Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic

Contribution: Data curation (equal), Writing - review & editing (equal);13. 1st Department of Internal Medicine, Faculty of Medicine in Pilsen, University Hospital Pilsen, Charles University, Pilsen, Czech Republic

Contribution: Data curation (equal);14. 1st Internal Clinic, Louis Pasteur University Hospital, Kosice, Slovakia

Contribution: Data curation (equal), Writing - review & editing (equal);15. 2nd Department of Internal Medicine, Faculty of Medicine, St. Ann University Hospital Brno, Masaryk University Brno, Brno, Czech Republic

Contribution: Data curation (equal);16. Department of Internal Medicine and Gastroenterology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic

Contribution: Data curation (equal);17. National Institute of Endocrinology and Diabetology, Lubochňa, Slovakia

Contribution: Data curation (equal);18. 4th Department of Internal medicine, Faculty of Medicine, University Hospital, Charles University, Hradec Kralove, Czech Republic

Abstract:In somatotroph pituitary tumours, somatostatin analogue (SSA) therapy outcomes vary throughout the studies. We performed an analysis of cohort of patients with acromegaly from the Czech registry to identify new prognostic and predictive factors. Clinical data of patients were collected, and complex immunohistochemical assessment of tumour samples was performed (SSTR1-5, dopamine D2 receptor, E-cadherin, AIP). The study included 110 patients. In 31, SSA treatment outcome was evaluated. Sparsely granulated tumours (SGST) differed from the other subtypes in expression of SSTR2A, SSTR3, SSTR5 and E-cadherin and occurred more often in young. No other clinical differences were observed. Trouillas grading system showed association with age, tumour size and SSTR2A expression. Factors significantly associated with SSA treatment outcome included age, IGF1 levels, tumour size and expression of E-cadherin and SSTR2A. In the group of SGST, poor SSA response was observed in younger patients with larger tumours, lower levels of SSTR2A and higher Ki67. We observed no relationship with expression of other proteins including AIP. No predictive value of E-cadherin was observed when tumour subtype was considered . Multiple additional factors apart from SSTR2A expression can predict treatment outcome in patients with acromegaly.
Keywords:acromegaly  PITNET  pituitary neoplasm  somatostatin receptor
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