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Grading Using Ki-67 Index and Mitotic Rate Increases the Prognostic Accuracy of Pancreatic Neuroendocrine Tumors

Philips, Prejesh, MD*; Kooby, David, A., MD; Maithel, Shishir, MD; Merchant, Nipun, B., MD; Weber, Sharon, M., MD§; Winslow, Emily, R., MD§; Ahmad, Syed, MD; Kim, Hong, J., MD; Scoggins, Charles, R., MD, MBA*; McMasters, Kelly, M., MD, PhD*; Martin, Robert, C.G., II, MD, PhD, FACS*

doi: 10.1097/MPA.0000000000000990
Original Articles

Objectives To measure the usefulness of Ki-67 proliferative index (Ki-67 index) as a prognostic variable for grading pancreatic neuroendocrine tumors.

Methods A multi-institutional prospective database comprising 350 patients. Grading based on mitotic activity (<2 mitoses/10 high-power fields, 2–20 and >20) and Ki-67 index (<3% per 10 high-power fields, 3%-20% and >20%). Final grade selected based on higher grade of either variable.

Results Most patients were in the less than 3% (n = 158) and 3% to 20% Ki-67 category (n = 107), with a minority being high-grade (Ki-67 > 20%, n = 27). Discordance between Ki-67 and mitotic rate was noted in 58 patients. On multivariate analysis, final-grade (grade 2: P = 0.010, hazard ratio [HR], 1.2; grade 3: P = 0.002; HR, 2.8), Ki-67, mitotic rate, and lymph node status were significant prognostic markers for overall survival (OS). For disease-free survival (DFS), only final-grade (grade 2: P = 0.05; HR, 1.4; grade 3: P = 0.009; HR, 2.3), Ki-67, mitotic rate, and margin status significantly predicted DFS. Ki-67 was a better model for OS and mitotic rate for DFS. Overall combined final grade was the best model based on HR.

Conclusion Ki-67 is a strong prognostic factor for OS and DFS and should be included in all pancreatic neuroendocrine tumor pathology.

From the *Department of Surgery, University of Louisville, Louisville, KY; †Department of Surgery, Emory University, Atlanta, GA; ‡Department of Surgery, University of Miami, Miami, FL; §Department of Surgery, University of Wisconsin, Madison, WI; ∥Department of Surgery, University of Cincinnati, Cincinnati, OH; and ¶Department of Surgery, University of North Carolina, Chapel Hill, NC.

Received for publication July 17, 2017; accepted December 11, 2017.

Address correspondence to: Robert C.G. Martin, II, MD, PhD, FACS, Division of Surgical Oncology, University of Louisville, 315 E Broadway – M10, Room 312, Louisville, KY 40202 (e-mail:

The authors declare no conflict of interest.

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