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Redefining the Ki-67 Index Stratification for Low-Grade Pancreatic Neuroendocrine Tumors: Improving Its Prognostic Value for Recurrence of Disease

  • Pancreatic Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

The Ki-67 index is an established prognostic marker for recurrence after resection of pancreatic neuroendocrine tumors (PanNETs) that groups tumors into three categories: low grade (< 3%), intermediate grade (3–20%), and high grade (> 20%). Given that the majority of resected PanNETs have a Ki-67 less than 3%, this study aimed to stratify this group further to predict disease recurrence more accurately.

Methods

The Ki-67 index was pathologically re-reviewed and scored by a pathologist blinded to all other clinicopathologic variables using tissue microarray blocks made in triplicate. All patients who underwent curative-intent resection of non-metastatic PanNETs at a single institution from 2000 to 2013 were included in the study. The primary outcome was recurrence-free survival (RFS).

Results

Of 113 patients with well-differentiated PanNETs resected, 83 had tissue available for pathologic re-review. The Ki-67 index was lower than 3% for 72 tumors (87%) and between 3 and 20% for 11 tumors (13%). Considering only Ki-67 less than 3%, the tumors were further stratified by Ki-67 into three groups: group A (< 1%, n = 43), group B (1–1.99%, n = 23), and group C (2–2.99%, n = 6). Compared with group A, groups B and C more frequently had advanced T stage (T3: 44% and 67% vs 12%; p = 0.003) and lymphovascular invasion (50% and 83% vs 23%; p = 0.007). Groups B and C had similar 1- and 3-year RFS, both less than group A. After combining groups B and C, a Ki-67 of 1–2.99% was associated with decreased RFS compared with group A (< 1%). This persisted in the multivariable analysis (hazard ratio [HR] 8.6; 95% confidence interval [CI] 1.0–70.7; p = 0.045), with control used for tumor size, margin-positivity, lymph node involvement, and advanced T stage.

Conclusions

PanNETs with a Ki-67 of 1–2.99% exhibit distinct biologic behavior and earlier disease recurrence than those with a Ki-67 lower than 1%. This new stratification scheme, if externally validated, should be incorporated into future grading systems to guide both surveillance protocols and treatment strategies.

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Acknowledgements

Funding in part was provided by the Katz Foundation.

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Authors and Affiliations

  1. Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA

    Alexandra G. Lopez-Aguiar MD, Cecilia G. Ethun MD, Lauren M. Postlewait MD, Maria C. Russell MD, David A. Kooby MD, Charles A. Staley MD, Shishir K. Maithel MD & Kenneth Cardona MD, FACS

  2. Department of Pathology, Winship Cancer Institute, Emory University, Atlanta, GA, USA

    Kristen Zhelnin MD & Alyssa Krasinskas MD

  3. Department of Hematology Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA

    Bassel F. El-Rayes MD

  4. Department of General Surgery, Emory University, Atlanta, GA, USA

    Juan M. Sarmiento MD

Authors
  1. Alexandra G. Lopez-Aguiar MD
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  2. Cecilia G. Ethun MD
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  3. Lauren M. Postlewait MD
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  4. Kristen Zhelnin MD
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  5. Alyssa Krasinskas MD
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  6. Bassel F. El-Rayes MD
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  11. Shishir K. Maithel MD
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  12. Kenneth Cardona MD, FACS
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Correspondence to Kenneth Cardona MD, FACS.

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Lopez-Aguiar, A.G., Ethun, C.G., Postlewait, L.M. et al. Redefining the Ki-67 Index Stratification for Low-Grade Pancreatic Neuroendocrine Tumors: Improving Its Prognostic Value for Recurrence of Disease. Ann Surg Oncol 25, 290–298 (2018). https://doi.org/10.1245/s10434-017-6140-8

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  • DOI: https://doi.org/10.1245/s10434-017-6140-8

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