ECE2018 Poster Presentations: Adrenal and Neuroendocrine Tumours Endocrine tumours and neoplasia (34 abstracts)
Clinical features of ‘dedifferentiation’ in advanced pancreatic neuroendocrine neoplasms: the experience of two centers of excellence
Krystallenia Alexandraki 1 , Simona Grozinsky-Glasberg 2 , Maria Kaltsatou 1 , Georgios Kyriakopoulos 3 , Chrysovalantis Vergadis 4 , Paris Pappas 4 , Vasiliki Mavroeidi 1 , Marina Tsoli 1 , Georgios Nikolopoulos 1 , Anna Angelousi 1 , Akrivi Kostopoulou 5 , Theodosia Choreftaki 5 , Dimitra Rondogianni 3 , Johanna Kassiani Delladetsima 6 & Gregory Kaltsas 1
1Endocrine Unit, 1st Department of Propaedeutic Medicine, Laiko University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece; 2Neuroendocrine Tumor Unit, Department of Endocrinology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; 3Department of Pathology, Evangelismos Hospital, Athens, Greece; 4Department of Radiology, Laiko General Hospital, Athens, Greece; 5Department of Pathology, ‘G. Gennimatas’ General Hospital, Athens, Greece; 6First Department of Pathology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Introduction: Neuroendocrine neoplasms (NENs) exhibit significant heterogeneity in growth rates. Clinical and histopathological dedifferentiation has been documented but their clinical characteristics have not been described.
Aim of the study: The identification of clinical features of a series of pancreatic NENs (pNENs) that developed dedifferentiation during their course.
Methods: Fourteen patients (eight males) with mean age(±S.D.): 54.8±12.4 years were recruited from two centers. Patients with documented disease progression were submitted to a new biopsy. Dedifferentiation was defined as histologically proven higher Ki-67 (%) able to increase the grade of neoplasm. Immunohistochemical analysis (IHC) for p53, β-catenin and E-cadherin were studied as markers of aggressive behavior.
Results: Twelve (85.7%) patients with a >10% change in Ki-67 had sporadic pNENs and 2 with <10% had pNEN in the context of MEN-1. At presentation, 1 (7.1%) patient had a NEN stage I, another stage III, 12(85.7%) had stage IV; 5 (35.7%) patients had a grade 1 NEN, 8 (57.1%) had a grade 2 NEN, and 1 (7.1%) had a low grade 3 (Ki-67:25%). After dedifferentiation 2 patients had low grade 2 (Ki-67<10%), 1 high grade 2, 3 (21.4%) had low grade 3(Ki-67<50%), and 8 (57.1%) had high grade 3 (Ki-67≥50%); metastatic sites included, only liver:6, liver and bone:1, liver and lymph node:4, liver, lymph node, peritoneal implants:1. All patients had a positive octreoscan; 5 had functional syndrome (two gastrinoma, one carcinoid syndrome, one insulinoma, one VIPoma). The time of dedifferentiation, five patients were under molecular-targeted treatment (everolimus or sunitinib) with or without somatostatin analogs, four chemotherapy, three peptide receptor radionuclide therapy (PRRTs), one chemotherapy and PRRTs and one follow-up only. Eight lines of treatment were registered. At the last follow-up, 6 (42.9%) patients were alive with an overall survival 81.1±72.2 (9.46–263.3) months. The progression free-survival (PFS) for 1st line treatment was the only factor to predict time to dedifferentiation. No factor studied predicted mortality or the magnitude of Ki-67 increase. IHC for p53 was abnormal in 80% (4/5) cases all after dedifferentiation while β-catenin and E-cadherin had unaltered pattern of expression.
Conclusions: Dedifferentiation of NENs is associated with a more aggressive behavior and worse overall survival. More studies are needed to clarify if p53 may be used as immunohistochemical marker of dedifferentiation.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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