Tumor-Infiltrating Lymphocytes Do Not Affect Ki-67 Labeling Index in a Series of Pancreatic Neuroendocrine Tumors (PanNETs)
Sabrina C Wentz, Chanjuan Shi, Chad M McCall, Rajni Sharma, Ralph H Hruban. Johns Hopkins Hospital, Baltimore, MD; Vanderbilt University Medical Center, Nashville, TN
Background: Pancreatic neuroendocrine tumors (PanNETs) show poor clinical outcomes, with 10-year overall survival of 45%. The World Health Organization (WHO) 2010 grading system for PanNETs permits the use of either mitotic rate or Ki-67/MIB-1 proliferative index (Grade 1: < 2 mitoses/10HPF or < 3% Ki-67 index; Grade 2: 2-20 mitoses/HPF or 3-20% Ki-67 index), which may lead to discordant grading by method used. We postulated that the presence of tumor-infiltrating lymphocytes, which may label for Ki-67, falsely elevates the Ki-67 labeling index in PanNETs with discordant grading.
Design: A dual immunohistochemical stain protocol was employed using the Ki-67 anti-CD45 antibodies (mouse monoclonal, anti-human CD45 Leucocyte Common Antigen (clone 2B11+PD7/27) and rabbit monoclonal anti-Ki67 (clone 30-9)) on 17 PanNETs with discordant grading resected at a single institution (1989-2009) with available histologic material. Ki-67+, CD45+, and Ki-67+/CD45+ labeling indices were obtained by averaging 10 high-powered fields per tumor and expressed as a percentage of total tumoral cells. Statistical analysis was performed using a paired T-test at 95% certainty.
Results: The average patient age was 54.2 years at diagnosis (58.8% female, 41.2% male), all with unifocal PanNETs (average size 4.3 cm) arising in the pancreatic head (47%, 8/17), uncinate (5.9%, 1/17), body (11.8%, 2/17), and tail (35.3%, 6/17). Using the Ki-67 labeling index cutoff of 3%, 35.3% (6/17) were Grade 1 and 64.7% (11/17) were Grade 2. The CD45 labeling indices for Grade 1 and 2 tumors were 7.4 ± 19.7% and 4.7 ± 11.1% (p=0.47). The Ki-67+/CD45+ labeling indices for Grade 1 and 2 tumors were 0.0029 ± 0.10% and 0.60 ± 3.6% (p=0.45).
Conclusions: These results suggest that tumor-infiltrating lymphocytes did not affect the Ki-67 labeling index in this series of PanNETs, and will require validation with a larger patient population.
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 205, Tuesday Morning