title: Ki-67 proliferative index predicts progression-free survival of patients with well-differentiated ileal neuroendocrine tumors.
abstract: Ki-67 proliferative index (Ki-67 index) is suggested to be an important prognostic variable and is included as one of the grading parameters for neuroendocrine tumors. The present study was undertaken to determine the usefulness of the Ki-67 index and the corresponding tumor grade in predicting progression-free survival (PFS) of patients with ileal well-differentiated neuroendocrine tumors (wNETs). Tumors from 57 patients with ileal wNETs were studied. Immunohistochemical staining for Ki-67 was performed on the primary as well as selected metastatic tumors and quantitated by computer-assisted image analysis using the Ariol system. The tumors were graded based on mitotic activity and Ki-67 index. Clinical and pathological variables affecting the PFS were analyzed. There were 29 women and 28 men, with a mean age of 59 years. At the time of initial presentation, 8 patients (14%) had localized disease (stages I and II), 29 patients (51%) had regional (nodal/mesenteric) spread (stage III), and 20 patients (35%) had distant metastasis (stage IV). Twelve patients experienced disease progression during subsequent follow-up. Patients with initial stage IV disease were more likely to experience disease progression (P = .005). Additionally, higher histological grade (as determined by Ki-67 index >2%) was associated with a decreased PFS (P = .001). Ki-67 index greater than 2% at either the primary site or the metastatic site was found to be the only significant predictor of PFS after consideration of all other variables in an adjusted analysis. In conclusion, the Ki-67 index predicts PFS of patients with ileal wNETs.
authors.affiliation: Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. dhalld@cshs.org
authors.forename: Deepti
authors.initials: D
authors.lastname: Dhall
authors.forename: Richard
authors.initials: R
authors.lastname: Mertens
authors.forename: Catherine
authors.initials: C
authors.lastname: Bresee
authors.forename: Rugvedita
authors.initials: R
authors.lastname: Parakh
authors.forename: Hanlin L
authors.initials: HL
authors.lastname: Wang
authors.forename: Marissa
authors.initials: M
authors.lastname: Li
authors.forename: Girish
authors.initials: G
authors.lastname: Dhall
authors.forename: Steven D
authors.initials: SD
authors.lastname: Colquhoun
authors.forename: Delma
authors.initials: D
authors.lastname: Ines
authors.forename: Fai
authors.initials: F
authors.lastname: Chung
authors.forename: Run
authors.initials: R
authors.lastname: Yu
authors.forename: Nicholas N
authors.initials: NN
authors.lastname: Nissen
authors.forename: Edward
authors.initials: E
authors.lastname: Wolin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D002276:Carcinoid Tumor / Q000378:metabolism / Q000473:pathology* / Q000556:secondary / Q000628:therapy; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007078:Ileal Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D007091:Image Processing, Computer-Assisted / Q000379:methods; D019394:Ki-67 Antigen / Q000378:metabolism*; D008113:Liver Neoplasms / Q000473:pathology / Q000556:secondary / Q000628:therapy; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D008940:Mitotic Index; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen