Increased (>20%) Ki67 Proliferation Index in Morphologically Well Differentiated Pancreatic Neuroendocrine Tumors (PanNETs) Correlates with Decreased Overall Survival
Olca Basturk, Zhaohai Yang, Laura H Tang, Ralph Hruban, Chad McCall, Volkan Adsay, Alyssa Krasinskas, Kee-Taek Jang, Andrew Bellizzi, Chanjuan Shi, David S Klimstra. Memorial Sloan-Kettering Cancer Center, New York, NY; Penn State Hershey MC, Hershey, PA; Johns Hopkins University, Baltimore, MD; Emory University, Atlanta, GA; University of Pittsburgh, Pittsburgh, PA; Samsung MC, Seoul, Korea; Brigham and Women's Hospital, Boston, MA; Vanderbilt University, Nashville, TN
Background: By WHO classification, PanNETs should be graded by mitotic rate and Ki67 proliferation index, with grade (G)2 defined as a mitotic rate of 2-20 mitoses/10 HPF or a Ki67 index of 3-20%. G3 is defined as a >20 mitoses/10 HPF or a Ki67 index of >20%. Given the fact that some PanNETs show discordance between mitotic rate and Ki67 index, we performed Ki-67 immunohistochemical labeling on well differentiated (WD) mitotic G2 PanNETs in our institutional databases and examined clinicopathologic features and survival outcomes.
Design: Morphologically WD PanNETs biopsied or surgically resected at our institutions from 1999-2012 were reviewed. The percentage of Ki67 positive cells was quantified either using image analysis or manual counting on camera-captured/printed images of Ki67 hot spots. Survival outcome was determined using the Social Security Death Index. For comparison, 39 morphologically poorly differentiated (either small cell or large cell type) neuroendocrine carcinomas (NECs) were retrieved, and similarly assessed for proliferation and survival.
Results: Of 65 mitotic G2 PanNETs, 23 were G3 based on Ki67 index (median=30%, 21%-65%). Overall, patients with grade-discordant PanNETs had a survival time shorter than grade-concordant G2 PanNETs (p=0.01) but longer than patients with poorly differentiated NECs (p=0.017), with grade-discordant tumors showing median survival of 32.3 mos and 5-yr survival of 22.1% (vs 62.7 mos and 60.5% for grade-concordant G2 PanNET, and 15.1 mos and 16.8% for NEC).
Conclusions: Our data support the notion that the mitotic rate and Ki67 index-based grades of PanNETs can be discordant, and when the Ki67 index is greater, the clinical outcome is significantly worse. We further demonstrate that WD PanNETs that are G3 by Ki-67 are still different from bona fide NECs, suggesting the current G3 can be further separated into G3 (WD PanNET with increased proliferation index) and poorly differentiated NEC.
Tuesday, March 5, 2013 1:30 PM
Proffered Papers: Section F, Tuesday Afternoon