Usefulness of Ki-67 for Predicting Metastatic Potential of Carcinoid Tumour of the Lung: A Study of 48 Cases
A Shibani, N Panjawani, A Arab, R Inculet, LW Stitt, JG Shepherd, MG Joseph. London Health Sciences Centre, London, ON, Canada
Background: Ki-67 is an emerging proliferation marker for the evaluation of high risk subsets of Lung Carcinoid Tumors (LCTs). The objectives of this study are 1) to evaluate the usefulness of Ki-67 index as well as mitoses and tumor size in predicting metastasis 2) to compare the Manual Conventional Method (MCM) and the Computer Assisted Image Analysis Method (CAIAM) for its calculation.
Design: Forty-eight patients with LCTs were studied from 1982-2007. For Ki-67 immunostudy two sections of tumor were stained (Vector laboratories; clone MM1). Digital images of 5000 cells were counted using a image processing software (Northern Eclipse version 7.0) and 2000 cells by MCM (Zeiss microscope, 40 x objective). Mitoses/10HPF were counted.
Results: The age of the patients ranged from 17-81 (mean 52, 18 M, 30 F). Of the 48 patients, 7 developed metastasis in lymph node (6), liver (1) or both (2). Median follow up for metastatic (MG) and non-metastatic groups (NMG) were 45 and 35 months respectively. The mean tumor size was 2.7 cm (range 0.5-9.5). 37 were typical carcinoids (TCs) and 11 atypical carcinoids (ACs) (Travis criteria). There was a strong correlation between Ki-67 index by MCM (1.5) and CIAM (0.75) (r = 0.929, P= .001). There were positive relationships between metastasis and carcinoid type (P=.039) and mitoses (≥2) (P=.017). Although not statistically significant, the mean Ki-67 index for ACs was higher than for TCs by both counting methods (0.95% vs. 0.72% by CIAM, P=.299; 2.32% vs.1.37% by MCM, P=.71). Similarly although not statistically significant, the mean Ki-67 index for MG was higher than for NMG (1.01% vs. 0.71% by CIAM, P=.281; 2.10% vs. 1.39% by MCM, P=.239). However when Ki-67 index data was categorized at various levels, there is suggestion of a useful cutoff (≥0.50%) to predict metastasis (P= .106 by CIAM, .166 by MCM). A significantly higher proportion of patients with mitosis ≥2 and Ki-67 index ≥0.50% had metastasis (P=.033) than other patients. Similarly patients with tumor size ≥3cm and Ki-67≥0.50% had a greater percentage of metastases than others (P=.039).
Conclusions: This study confirms that mitoses ≥2 is a powerful predictor of metastasis in LCTs. Analysis of Ki-67 index along with mitoses may be a useful adjunct for predicting metastasis in LCTs for which adjuvant therapy may be considered.
Wednesday, March 24, 2010 9:30 AM
Poster Session V # 238, Wednesday Morning