Comparison of Three Ki-67 Index Quantification Methods and Clinical Significance in Pancreatic Neuroendocrine Tumors
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Comparison of Three Ki-67 Index Quantification Methods and Clinical Significance in Pancreatic Neuroendocrine Tumors Trynda N. Kroneman 1 & Jesse S. Voss 1 & Christine M. Lohse 2 & Tsung-Teh Wu 1 & Thomas C. Smyrk 1 & Lizhi Zhang 1
# Springer Science+Business Media New York 2015
Abstract The Ki-67 index is essential in the pathological reports for pancreatic neuroendocrine tumors. There are three methods to determine the Ki-67 index including eyeball estimation, manual counting, or automated digital imaging analysis. The goal of this study was to compare the three quantification methods with the clinical outcome to determine the best method for clinical practice. Ki-67 immunostaining was performed on 97 resected pancreatic neuroendocrine tumors. The three methods of quantification were employed: (1) an average of eyeball estimation by three pathologists; (2) manual counting of at least 500 tumor cells; and (3) digital imaging analysis quantitation by selecting 8–10 hot spot regions. All tumors were graded according to the 2010 WHO grading system. The three quantification methods for the Ki-67 index had almost perfect agreement. The concordance between manual counting and digital imaging analysis and between manual counting and average eyeball estimation were 0.97 and 0.88, respectively. The concordance among the three pathologists’ eyeball estimation was 0.86. All three methods correlated with patients’ survival using the 2010 WHO grading system. Eyeball estimation scores were significantly less than those of the other two methods and tended to downgrade more tumors to grade 1, but they had higher predictive ability for survival and recurrence. The WHO system using the mitotic rate could also separate patients with different survival
* Lizhi Zhang [email protected] 1
Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
2
Division of Biomedical Statistics and Informatics, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
and even downgraded more tumors to grade 1. The results suggest the necessity of a consensus among pathologists for the method to determine the Ki-67 index and proper cutoff of the Ki-67 index for better clinical correlation. Keywords Pancreatic neuroendocrine tumor . Ki-67 . Mitosis . Digital imaging analysis . Prognosis
Introduction The biologic behavior of a pancreatic neuroendocrine tumor (PNET) is often difficult to predict. Tumor cell proliferation probably is the most important prognostic factor for PNET [1–5]. Essentially all grading systems for PNET have included either mitoses and/or the Ki-67 index [5–10]. Indeed, the latest 2010 WHO classification system for gastrointestinal and pancreatic neuroendocrine tumors is purely based on either mitoses and/or the Ki-67 index [11, 12]. The Ki-67 index is becoming a mandatory component of pathology reports for all neuroendocrine tumors [13]. Particularly, the Ki-67 index is very useful in small biopsy specimens or for metastases in which a la
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