title: Hormone profiling, WHO 2010 grading, and AJCC/UICC staging in pancreatic neuroendocrine tumor behavior.
abstract: Pancreatic neuroendocrine tumors (pNETs) are the second most common pancreatic neoplasms, exhibiting a complex spectrum of clinical behaviors. To examine the clinico-pathological characteristics associated with long-term prognosis we reviewed 119 patients with pNETs treated in a tertiary referral center using the WHO 2010 grading and the American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) staging systems, with a median follow-up of 38 months. Tumor size, immunohistochemistry (IHC) profiling and patient characteristics-determining stage were analyzed. Primary clinical outcomes were disease progression or death. The mean age at presentation was 52 years; 55% were female patients, 11% were associated with MEN1 (multiple endocrine neoplasia 1) or VHL (Von Hippel-Lindau); mean tumor diameter was 3.3 cm (standard deviation, SD) (2.92). The clinical presentation was incidental in 39% with endocrine hypersecretion syndromes in only 24% of cases. Nevertheless, endocrine hormone tissue immunoreactivity was identified in 67 (56.3%) cases. According to WHO 2010 grading, 50 (42%), 38 (31.9%), and 3 (2.5%) of tumors were low grade (G1), intermediate grade (G2), and high grade (G3), respectively. Disease progression occurred more frequently in higher WHO grades (G1: 6%, G2: 10.5%, G3: 67%, P = 0.026) and in more advanced AJCC stages (I: 2%, IV: 63%, P = 0.033). Shorter progression free survival (PFS) was noted in higher grades (G3 vs. G2; 21 vs. 144 months; P = 0.015) and in more advanced AJCC stages (stage I: 218 months, IV: 24 months, P < 0.001). Liver involvement (20 vs. 173 months, P < 0.001) or histologically positive lymph nodes (33 vs. 208 months, P < 0.001) were independently associated with shorter PFS. Conversely, tissue endocrine hormone immunoreactivity, independent of circulating levels was significantly associated with less aggressive disease. Age, gender, number of primary tumors, and heredity were not significantly associated with prognosis. Although the AJCC staging and WHO 2010 grading systems are useful in predicting disease progression, tissue endocrine hormone profiling provides additional information of potentially important prognostic value.
authors.affiliation: Department of Medicine, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
authors.forename: Emilie
authors.initials: E
authors.lastname: Morin
authors.forename: Sonia
authors.initials: S
authors.lastname: Cheng
authors.forename: Ozgur
authors.initials: O
authors.lastname: Mete
authors.forename: Stefano
authors.initials: S
authors.lastname: Serra
authors.forename: Paula B
authors.initials: PB
authors.lastname: Araujo
authors.forename: Sara
authors.initials: S
authors.lastname: Temple
authors.forename: Sean
authors.initials: S
authors.lastname: Cleary
authors.forename: Steven
authors.initials: S
authors.lastname: Gallinger
authors.forename: Paul D
authors.initials: PD
authors.lastname: Greig
authors.forename: Ian
authors.initials: I
authors.lastname: McGilvray
authors.forename: Alice
authors.initials: A
authors.lastname: Wei
authors.forename: Sylvia L
authors.initials: SL
authors.lastname: Asa
authors.forename: Shereen
authors.initials: S
authors.lastname: Ezzat
mesh_terms: D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006728:Hormones / Q000378:metabolism*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000556:secondary; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D018358:Neuroendocrine Tumors / Q000175:diagnosis / Q000188:drug therapy / Q000473:pathology* / Q000556:secondary; D015282:Octreotide / Q000627:therapeutic use; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000473:pathology*; D011379:Prognosis; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D006728:Hormones; D015282:Octreotide
keywords: Carcinoid; gastrinoma; insulinoma; neuroendocrine tumors; pNET