Krystallenia I Alexandraki1,2, Maria Kaltsatou3, Georgios Kyriakopoulos3,4, Vasiliki Mavroeidi5, Akrivi Kostopoulou6, Karine Atlan7, Stamatios Theocharis3,8, Guido Rindi9,10,11, Ashley B Grossman12,13,14,15, Simona Grozinsky-Glasberg16, Gregory A Kaltsas3,5. 1. ENETS Center of Excellence, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. alexandrakik@gmail.com. 2. 2nd Department of Surgery, Medical School, National and Kapodistrian University of Athens, Athens, Greece. alexandrakik@gmail.com. 3. ENETS Center of Excellence, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. 4. Department of Pathology, Evaggelismos Hospital, Athens, Greece. 5. Endocrine Unit, 1st Department of Propaedeutic Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. 6. Department of Pathology, "G. Gennimatas" General Hospital, Athens, Greece. 7. Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. 8. First Department of Pathology, Medical School, National and Kapodistrian University of Athens, Athens, Greece. 9. Anatomic Pathology Section, Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, Roma, Italy. 10. Anatomic Pathology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy. 11. ENETS Center of Excellence, Roma, Italy. 12. Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK. 13. University of Oxford, Oxford, UK. 14. Green Templeton College, Oxford, UK. 15. ENETS Center of Excellence, Royal Free London, London, UK. 16. Neuroendocrine Tumor Unit, ENETS Center of Excellence, Department of Endocrinology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Abstract
PURPOSE: Neuroendocrine neoplasms (NENs) differ in their biological behavior and growth potential in a way that can be predicted using histological classification and grading systems. A subset of pancreatic NENs (pNENs) may develop a more aggressive phenotype during the course of the disease, associated with an increase in the Ki-67 proliferation index (PI). The purpose of the study was to present the clinical characteristics of these patients. METHODS: Using re-biopsy of growing lesions, we investigated the increase in Ki-67 PI sufficient to change initial grading (G). RESULTS: Of 264 patients with well differentiated (WD) pNENs who showed progressive disease during follow-up, 15 (6%) exhibited an increase in Ki-67 PI at a median time 36.8 (9.3-255.8) months. All neoplasms had WD-morphology: five had G1 (Ki-67 median value 1%), nine G2 (median value 5%), one G3 (25%) grades. Upon change of Ki-67 PI, 3 patients had G2 (8%) and 12 G3 (57.5%) NENs, while all retained their WD-morphology. At last follow-up, eight patients were alive with a median overall survival (OS) of 52.5 (9.5-264.3) months. Μedian OS was shorter in patients who had a change in Ki-67 PI before 36 months compared to those who had a change of Ki-67 PI at a later stage (27.5 95%CI: 11.88-43.06 vs. 120.87 95%CI: 96.05-145.69; log-rank p = 0.018). CONCLUSIONS: During the course of their disease, 6% patients with progressive pNENs develop an increase in Ki-67 PI resulting in an increase in grading status while maintaining their morphology. This process is associated with worse OS when it occurs at an early stage.
PURPOSE:Neuroendocrine neoplasms (NENs) differ in their biological behavior and growth potential in a way that can be predicted using histological classification and grading systems. A subset of pancreatic NENs (pNENs) may develop a more aggressive phenotype during the course of the disease, associated with an increase in the Ki-67 proliferation index (PI). The purpose of the study was to present the clinical characteristics of these patients. METHODS: Using re-biopsy of growing lesions, we investigated the increase in Ki-67 PI sufficient to change initial grading (G). RESULTS: Of 264 patients with well differentiated (WD) pNENs who showed progressive disease during follow-up, 15 (6%) exhibited an increase in Ki-67 PI at a median time 36.8 (9.3-255.8) months. All neoplasms had WD-morphology: five had G1 (Ki-67 median value 1%), nine G2 (median value 5%), one G3 (25%) grades. Upon change of Ki-67 PI, 3 patients had G2 (8%) and 12 G3 (57.5%) NENs, while all retained their WD-morphology. At last follow-up, eight patients were alive with a median overall survival (OS) of 52.5 (9.5-264.3) months. Μedian OS was shorter in patients who had a change in Ki-67 PI before 36 months compared to those who had a change of Ki-67 PI at a later stage (27.5 95%CI: 11.88-43.06 vs. 120.87 95%CI: 96.05-145.69; log-rank p = 0.018). CONCLUSIONS: During the course of their disease, 6% patients with progressive pNENs develop an increase in Ki-67 PI resulting in an increase in grading status while maintaining their morphology. This process is associated with worse OS when it occurs at an early stage.
Entities:
Keywords:
Change of Ki-67 PI; De-differentiation; Ki-67; Neuroendocrine neoplasms; p53