Evaluation of Ki-67 index in EUS–FNA specimens for the assessment of malignancy risk in pancreatic neuroendocrine tumors

Background and study aim: Malignancy in pancreatic neuroendocrine tumors (PNETs) is graded by assessing the resected specimens according to the World Health Organization (WHO) 2010 criteria. The feasibility of such grading using endoscopic ultrasound-guided fine-needle aspiration (EUS–FNA) specimens remains unclear. The aim of this study was to ascertain the optimal method of measuring the Ki-67 index in EUS–FNA specimens, using resected specimens as the criterion standard.

Patients and methods: A total of 58 consecutive patients diagnosed with PNETs between March 1998 and May 2011 were included. The study measured intratumoral Ki-67 index heterogeneity, concordance rates of PNET grading by EUS–FNA with grade of the resected tumor, optimal method of measuring the Ki-67 index in EUS–FNA specimens, and survival analysis based on EUS–FNA specimen grading.

Results: Intratumoral dispersion of Ki-67 index in resected specimens was 0.033 for Grade 1 and 0.782 for Grade 2 tumors (P < 0.001). Concordance rates for WHO classification between EUS–FNA and resected specimens were 74.0 % using the mean Ki-67 index in EUS–FNA specimens and 77.8 % using the highest Ki-67 index. The concordance rate rose to 90 % when EUS–FNA samples with less than 2000 tumor cells were excluded (26 % of EUS–FNA cases). The Kaplan–Meier survival curves were significantly stratified by the EUS–FNA grading of PNETs with 5-year survival rates of 100 %, 58.3 %, and 0 %, for Grade 1, Grade 2, and neuroendocrine carcinoma (NEC) tumors, respectively.

Conclusions: Grading of PNETs by the highest Ki-67 index in EUS–FNA specimens with adequate cellularity has a high concordance with grading of resected specimens, and can predict long term patient survival with high accuracy.

• References

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