Skip to main content

Grading of well-differentiated pancreatic neuroendocrine tumors is improved by the inclusion of both Ki67 proliferative index and mitotic rate.

Publication ,  Journal Article
McCall, CM; Shi, C; Cornish, TC; Klimstra, DS; Tang, LH; Basturk, O; Mun, LJ; Ellison, TA; Wolfgang, CL; Choti, MA; Schulick, RD; Edil, BH; Hruban, RH
Published in: Am J Surg Pathol
November 2013

The grading system for pancreatic neuroendocrine tumors (PanNETs) adopted in 2010 by the World Health Organization (WHO) mandates the use of both mitotic rate and Ki67/MIB-1 index in defining the proliferative rate and assigning the grade. In cases when these measures are not concordant for grade, it is recommended to assign the higher grade, but specific data justifying this approach do not exist. Thus, we counted mitotic figures and immunolabeled, using the Ki67 antibody, 297 WHO mitotic grade 1 and 2 PanNETs surgically resected at a single institution. We quantified the Ki67 proliferative index by marking at least 500 cells in "hot spots" and by using digital image analysis software to count each marked positive/negative cell and then compared the results with histologic features and overall survival. Of 264 WHO mitotic grade 1 PanNETs, 33% were WHO grade 2 by Ki67 proliferative index. Compared with concordant grade 1 tumors, grade-discordant tumors were more likely to have metastases to lymph node (56% vs. 34%) (P<0.01) and to distant sites (46% vs. 12%) (P<0.01). Discordant mitotic grade 1 PanNETs also showed statistically significantly more infiltrative growth patterns, perineural invasion, and small vessel invasion. Overall survival was significantly different (P<0.01), with discordant mitotic grade 1 tumors showing a median survival of 12 years compared with 16.7 years for concordant grade 1 tumors. Conversely, mitotic grade 1/Ki67 grade 2 PanNETs showed few significant differences from tumors that were mitotic grade 2 and either Ki67 grade 1 or 2. Our data demonstrate that mitotic rate and Ki67-based grades of PanNETs are often discordant, and when the Ki67 grade is greater than the mitotic grade, clinical outcomes and histopathologic features are significantly worse than concordant grade 1 tumors. Patients with discordant mitotic grade 1/Ki67 grade 2 tumors have shorter overall survival and larger tumors with more metastases and more aggressive histologic features. These data strongly suggest that Ki67 labeling be performed on all PanNETs in addition to mitotic rate determination to define more accurately tumor grade and prognosis.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Am J Surg Pathol

DOI

EISSN

1532-0979

Publication Date

November 2013

Volume

37

Issue

11

Start / End Page

1671 / 1677

Location

United States

Related Subject Headings

  • Young Adult
  • Proportional Hazards Models
  • Prognosis
  • Predictive Value of Tests
  • Pathology
  • Pancreatic Neoplasms
  • Neuroendocrine Tumors
  • Neoplasm Invasiveness
  • Neoplasm Grading
  • Mitotic Index
 

Citation

APA
Chicago
ICMJE
MLA
NLM
McCall, C. M., Shi, C., Cornish, T. C., Klimstra, D. S., Tang, L. H., Basturk, O., … Hruban, R. H. (2013). Grading of well-differentiated pancreatic neuroendocrine tumors is improved by the inclusion of both Ki67 proliferative index and mitotic rate. Am J Surg Pathol, 37(11), 1671–1677. https://doi.org/10.1097/PAS.0000000000000089
McCall, Chad M., Chanjuan Shi, Toby C. Cornish, David S. Klimstra, Laura H. Tang, Olca Basturk, Liew Jun Mun, et al. “Grading of well-differentiated pancreatic neuroendocrine tumors is improved by the inclusion of both Ki67 proliferative index and mitotic rate.Am J Surg Pathol 37, no. 11 (November 2013): 1671–77. https://doi.org/10.1097/PAS.0000000000000089.
McCall CM, Shi C, Cornish TC, Klimstra DS, Tang LH, Basturk O, et al. Grading of well-differentiated pancreatic neuroendocrine tumors is improved by the inclusion of both Ki67 proliferative index and mitotic rate. Am J Surg Pathol. 2013 Nov;37(11):1671–7.
McCall, Chad M., et al. “Grading of well-differentiated pancreatic neuroendocrine tumors is improved by the inclusion of both Ki67 proliferative index and mitotic rate.Am J Surg Pathol, vol. 37, no. 11, Nov. 2013, pp. 1671–77. Pubmed, doi:10.1097/PAS.0000000000000089.
McCall CM, Shi C, Cornish TC, Klimstra DS, Tang LH, Basturk O, Mun LJ, Ellison TA, Wolfgang CL, Choti MA, Schulick RD, Edil BH, Hruban RH. Grading of well-differentiated pancreatic neuroendocrine tumors is improved by the inclusion of both Ki67 proliferative index and mitotic rate. Am J Surg Pathol. 2013 Nov;37(11):1671–1677.

Published In

Am J Surg Pathol

DOI

EISSN

1532-0979

Publication Date

November 2013

Volume

37

Issue

11

Start / End Page

1671 / 1677

Location

United States

Related Subject Headings

  • Young Adult
  • Proportional Hazards Models
  • Prognosis
  • Predictive Value of Tests
  • Pathology
  • Pancreatic Neoplasms
  • Neuroendocrine Tumors
  • Neoplasm Invasiveness
  • Neoplasm Grading
  • Mitotic Index