title: Usefulness of Ki-67, Mitoses, and Tumor Size for Predicting Metastasis in Carcinoid Tumors of the Lung: A Study of 48 Cases at a Tertiary Care Centre in Canada.
abstract: Background. Evaluation of Ki-67 index in lung carcinoid tumors (LCTs) has been of interest in order to identify high risk subsets. Our objectives are (1) to evaluate the usefulness of Ki-67 index, mitoses, and tumor size in predicting metastasis and (2) to compare the Manual Conventional Method (MCM) and the Computer Assisted Image Analysis Method (CIAM) for Ki-67 calculation. Methods. We studied 48 patients with LCTs from two academic centres in Canada. For Ki-67 calculation, digital images of 5000 cells were counted using an image processing software and 2000 cells by MCM. Mitoses/10 HPF was counted. Results. We had 37 typical carcinoids (TCs) and 11 atypical carcinoids (ACs). 7/48 patients developed metastasis. There was a positive relationship between metastasis and carcinoid type (P = 0.039) and metastasis and mitoses (≥2) (P = 0.017). Although not statistically significant, the mean Ki-67 index for ACs was higher than for TCs (0.95% versus 0.72%, CIAM, P = 0.299). Similarly, although not statistically significant, the mean Ki-67 index for metastatic group (MG) was higher than for nonmetastatic group (NMG) (1.01% versus 0.71% by CIAM, P = 0.281). However when Ki-67 index data was categorized at various levels, there is suggestion of a useful cutoff (≥0.50%) to predict metastasis (P = 0.106, CIAM). A significantly higher proportion of patients with mitosis ≥2 and Ki-67 index ≥0.50% had metastasis (P = 0.033) compared to other patients. Similarly patients with tumor size ≥3 cm and Ki-67 ≥0.50% had a greater percentage of metastases than others (P = 0.039). Although there was a strong correlation between two (MCM versus CIAM) counting methods (r = 0.929, P = 0.001), overall the calculated Ki-67 index was slightly higher by MCM (range 0 to 6.4, mean 1.5) compared to CIAM (range 0 to 2.9, mean 0.75). Conclusion. This study confirms that mitoses ≥2 is a powerful predictor of metastasis in LCTs. Although this is a small sample size, there is suggestion that analysis of Ki-67 index along with mitoses and tumor size may be a useful adjunct for predicting metastasis in LCTs.
authors.affiliation: Department of Pathology, London Health Sciences Centre, Western University, London, ON, Canada; Department of Pathology, University Hospital, 339 Windermere Road, London, ON, Canada N6A 5A5.
authors.forename: M G
authors.initials: MG
authors.lastname: Joseph
authors.affiliation: Department of Pathology, London Health Sciences Centre, Western University, London, ON, Canada; Brantford General Hospital, ON, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Shibani
authors.affiliation: Pathologist assistant program, London Health Sciences Centre, Western University, Canada; University of Calgary, Canada.
authors.forename: N
authors.initials: N
authors.lastname: Panjwani
authors.affiliation: Division of Respirology, University of Ottawa, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Arab
authors.affiliation: Department of Pathology, London Health Sciences Centre, Western University, London, ON, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Shepherd
authors.affiliation: Division of Respirology, University of Ottawa, Canada.
authors.forename: L W
authors.initials: LW
authors.lastname: Stitt
authors.affiliation: Department of Thoracic Surgery, London Health Sciences Centre, Western University, London, ON, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Inculet