title: Limited role of Ki-67 proliferative index in predicting overall short-term survival in patients with typical and atypical pulmonary carcinoid tumors.
abstract: Pulmonary carcinoid tumors are currently classified as typical or atypical based on the mitotic index (2 per 10 hpf) and/or the presence of necrosis. Following incorporation of the Ki-67 index into the classification of GI carcinoid tumors, our oncologists have also been requesting this test as part of the work-up of pulmonary carcinoid tumors although there are currently no established criteria for interpreting Ki-67 index in these neoplasms. We utilized the Ariol(®) SL50 Image Analyzer system to measure the Ki-67 index in 101 pulmonary carcinoid tumors (78 typical and 23 atypical) and then correlated the Ki-67 index and the histological diagnoses in univariate and multivariable analysis with overall survival. The mean Ki-67 indices for the typical carcinoids (3.7 s.d.± 4.0) and the atypical carcinoids (18.8 s.d.± 17.1) were significantly different (P<0.001) although the frequency distributions of Ki-67 indices in the two groups overlapped considerably. Receiver operating characteristic curve analysis showed that a Ki-67 index cutoff value of 5% provided the best fit for specificity and sensitivity in predicting overall survival. Histological diagnosis and the Ki-67 index cutoff of 5% were each independently strong predictors of survival (P<0.001 and P=0.003, respectively). When considered together in multivariable analysis, histological diagnosis was the stronger predictor of overall survival and a Ki-67 index cutoff of 5% did not provide additional significant predictive survival information within either the typical carcinoid or the atypical carcinoid patient group. A few typical carcinoid patients with Ki-67 indices of 5% appeared to have worse survival after 5 years than those with Ki-67 indices <5%, but the data set was insufficiently powered to further analyze this. These findings do not provide best evidence for the routine use of Ki-67 index to prognosticate overall short-term survival in patients with pulmonary carcinoid tumors.
authors.affiliation: Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. walts@cshs.org
authors.forename: Ann E
authors.initials: AE
authors.lastname: Walts
authors.forename: Delma
authors.initials: D
authors.lastname: Ines
authors.forename: Alberto M
authors.initials: AM
authors.lastname: Marchevsky
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002140:California / Q000453:epidemiology; D002276:Carcinoid Tumor / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D049109:Cell Proliferation; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D012189:Retrospective Studies; D015996:Survival Rate; D013997:Time Factors; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen