title: Evaluation of diagnostic and prognostic significance of Ki-67 index in pulmonary carcinoid tumours.
abstract: BACKGROUND
  Pulmonary carcinoid (PC) tumours are classified as either typical (TC) or atypical (AC) according to mitotic index (MI) and presence of necrosis. The aim of this study was to analyse the diagnostic and prognostic values of the Ki-67 index in PC.
  
  
  METHODS
  Between January 2001 and March 2015, we evaluated 94 consecutive patients with a confirmed diagnosis of TC (n = 75) or AC (n = 19) at our institution. Diagnostic histology was centrally reviewed by a local expert neuroendocrine pathologist, with assessment of Ki-67, MI, and necrosis.
  
  
  RESULTS
  Median patient follow-up was 35 months. Eighty-four patients who underwent curative surgical resection were included in the survival analysis for identification of prognostic factors. Ki-67 index showed high diagnostic accuracy to predict histological subtype when assessed by receiver operator characteristic curves with an area under the curve of 0.923 (95% CI 0.852-0.995, p < 0.001). Multivariate analysis showed that MI, Ki-67 index, and the presence or absence of necrosis were independent prognostic factors for relapse-free survival. Combination of MI, Ki-67, and necrosis led to the classification of patients into four different prognostic groups (very low, low, intermediate, and high risks of relapse).
  
  
  CONCLUSIONS
  The current study proposes the incorporation of Ki-67 index in the prognostic classification of PC tumours. Due to the limited number of patients and length of follow-up, the current model needs validation by larger cohort studies. Nevertheless, our results suggest that Ki-67 index and MI have continuous effect on prognosis. Prognostic models incorporating multiple cutoffs of Ki-67 and MI might better predict outcome and inform clinical decisions.
authors.affiliation: Department of Medical Oncology, The Christie NHS Foundation Trust, 550 Wilmslow Road, Manchester, M20 4BX, UK.|Institute of Cancer Studies, University of Manchester, Manchester, UK.
authors.forename: V
authors.initials: V
authors.lastname: Clay
authors.affiliation: Department of Medical Oncology, The Christie NHS Foundation Trust, 550 Wilmslow Road, Manchester, M20 4BX, UK.
authors.forename: G
authors.initials: G
authors.lastname: Papaxoinis
authors.affiliation: Department of Medical Oncology, The Christie NHS Foundation Trust, 550 Wilmslow Road, Manchester, M20 4BX, UK.
authors.forename: B
authors.initials: B
authors.lastname: Sanderson
authors.affiliation: Department of Medical Oncology, The Christie NHS Foundation Trust, 550 Wilmslow Road, Manchester, M20 4BX, UK.|Institute of Cancer Studies, University of Manchester, Manchester, UK.
authors.forename: J W
authors.initials: JW
authors.lastname: Valle
authors.affiliation: Department of Medical Oncology, The Christie NHS Foundation Trust, 550 Wilmslow Road, Manchester, M20 4BX, UK.
authors.forename: M
authors.initials: M
authors.lastname: Howell
authors.affiliation: Department of Medical Oncology, The Christie NHS Foundation Trust, 550 Wilmslow Road, Manchester, M20 4BX, UK.
authors.forename: A
authors.initials: A
authors.lastname: Lamarca
authors.affiliation: Department of Cardiothoracic Surgery, University Hospital of South Manchester, Manchester, M23 9LT, UK.
authors.forename: P
authors.initials: P
authors.lastname: Krysiak
authors.affiliation: Department of Thoracic Pathology, University Hospital of South Manchester, Manchester, M23 9LT, UK.
authors.forename: P
authors.initials: P
authors.lastname: Bishop
authors.affiliation: Institute of Cancer Studies, University of Manchester, Manchester, UK.|Department of Histopathology, The Christie NHS Foundation Trust, Manchester, M20 4BX, UK.
authors.forename: D
authors.initials: D
authors.lastname: Nonaka
authors.affiliation: Department of Medical Oncology, The Christie NHS Foundation Trust, 550 Wilmslow Road, Manchester, M20 4BX, UK. Was.Mansoor@christie.nhs.uk.|Institute of Cancer Studies, University of Manchester, Manchester, UK. Was.Mansoor@christie.nhs.uk.
authors.forename: W
authors.initials: W
authors.lastname: Mansoor
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000032:analysis*; D002276:Carcinoid Tumor / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000032:analysis*; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008940:Mitotic Index; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen
keywords: Atypical; Ki-67; Neuroendocrine tumours; Prognosis; Pulmonary carcinoids; Typical