@article{3076377,
    title = "Distinctive features of pancreatic neuroendocrine neoplasms exhibiting an increment in proliferative activity during the course of the disease",
    author = "Alexandraki, K.I. and Kaltsatou, M. and Kyriakopoulos, G. and Mavroeidi, V. and Kostopoulou, A. and Atlan, K. and Theocharis, S. and Rindi, G. and Grossman, A.B. and Grozinsky-Glasberg, S. and Kaltsas, G.A.",
    journal = "Endocrine Development",
    year = "2021",
    volume = "72",
    number = "1",
    pages = "279-286",
    publisher = "Springer-Verlag",
    doi = "10.1007/s12020-020-02540-w",
    keywords = "everolimus;  protein p53;  Ki 67 antigen, adult;  aged;  Article;  cancer grading;  cancer surgery;  cell structure;  clinical feature;  cohort analysis;  disease course;  disease exacerbation;  female;  follow up;  histopathology;  human;  human tissue;  immunohistochemistry;  major clinical study;  male;  middle aged;  morphology;  neuroendocrine tumor;  overall survival;  pancreas tumor;  priority journal;  proliferation index;  protein expression;  retrospective study;  survival time;  tumor biopsy;  very elderly;  cancer staging;  diagnostic test;  neuroendocrine tumor;  pancreas tumor;  pathology;  prognosis, Diagnostic Tests, Routine;  Humans;  Ki-67 Antigen;  Neoplasm Grading;  Neoplasm Staging;  Neuroendocrine Tumors;  Pancreatic Neoplasms;  Prognosis",
    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. © 2020, Springer Science+Business Media, LLC, part of Springer Nature."
}