title: Subgroup analysis of patients with G2 gastroenteropancreatic neuroendocrine tumors.
abstract: Neuroendocrine tumors (NET) are malignancies with an increasing incidence rate. NETs are graded or classified by the expression level of Ki67, a proliferation marker in Grade 1 and 2 tumors. Out of 120 patients who visited our hospital between 2003 and 2012, 40 were classified as G2 NET. This study was mainly designed to investigate a new threshold for optimising the Ki67 system. Patients were subdivided into two new groups according to Ki67 (group 1 = 3-9%, group 2 = 10-20%). Twenty-five patients were allocated to group 1 and 15 to group 2. The primary tumor originated in 46% from the foregut and 68% NET were functionally active. Patients were treated in 88 versus 60% by surgery, 48 versus 80% by somatostatin analogs, 0 versus 20% by chemotherapy, 2,5 versus 0% by Everolimus and 32 versus 47% underwent peptide receptor radionuclide therapy. Group 1 patients showed a significantly (p = 0.01) better survival compared with group 2 and also a significant difference of Chromogranin A (p = 0.03) and alkaline phosphatase (p = 0.01). In addition, all patients with elevated lactate dehydrogenase showed a significantly (p = 0.03) shorter survival. Prognostic relevance of G2 NETs may be improved by using a new boundary. Patients with Ki67 of 3-9% showed a better response to current treatment methods and significantly longer survival compared to group 2. Thus, our data clearly show that patients with higher G2 proliferation index should be treated differently. Finally, LDH has been found to be a new prognostic factor in patients with G2 NET.
authors.affiliation: a Department of Internal Medicine I, University Hospital , Tübingen, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Hauck
authors.affiliation: a Department of Internal Medicine I, University Hospital , Tübingen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Bitzer
authors.affiliation: a Department of Internal Medicine I, University Hospital , Tübingen, Germany.
authors.forename: Nisar
authors.initials: N
authors.lastname: Malek
authors.affiliation: a Department of Internal Medicine I, University Hospital , Tübingen, Germany.
authors.forename: Ruben R
authors.initials: RR
authors.lastname: Plentz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000097:blood*; D014408:Biomarkers, Tumor; D053379:Chromogranin A / Q000097:blood*; D016208:Databases, Factual; D005260:Female; D006801:Humans; D007414:Intestinal Neoplasms / Q000145:classification / Q000401:mortality / Q000628:therapy*; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000032:analysis*; D007770:L-Lactate Dehydrogenase / Q000097:blood*; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000145:classification / Q000401:mortality / Q000628:therapy*; D010190:Pancreatic Neoplasms / Q000145:classification / Q000401:mortality / Q000628:therapy*; D011379:Prognosis; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000145:classification / Q000401:mortality / Q000628:therapy*; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D053379:Chromogranin A; D019394:Ki-67 Antigen; D007770:L-Lactate Dehydrogenase; D000469:Alkaline Phosphatase
keywords: G2; Ki67; NET; survival; therapy