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


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.
Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan.
Toshiyuki
T
Hasegawa
Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan.
Kenji
K
Yamao
Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan.
Susumu
S
Hijioka
Department of Medical Hepatology, Institute of Liver and Biliary Sciences, Delhi, India.
Vikram
V
Bhatia
Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan.
Nobumasa
N
Mizuno
Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan.
Kazuo
K
Hara
Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan.
Hiroshi
H
Imaoka
Department of Endoscopy, Aichi Cancer Center Hospital, Nagoya, Japan.
Yasumasa
Y
Niwa
Department of Endoscopy, Aichi Cancer Center Hospital, Nagoya, Japan.
Masahiro
M
Tajika
Department of Endoscopy, Aichi Cancer Center Hospital, Nagoya, Japan.
Shinya
S
Kondo
Department of Endoscopy, Aichi Cancer Center Hospital, Nagoya, Japan.
Tutomu
T
Tanaka
Department of Gastrointestinal Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.
Yasuhiro
Y
Shimizu
Department of Gastrointestinal Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.
Taira
T
Kinoshita
Department of Gastroenterology and Hepatology, Kochi Medical School, Kochi, Japan.
Takuhiro
T
Kohsaki
Department of Gastroenterology and Hepatology, Kochi Medical School, Kochi, Japan.
Isao
I
Nishimori
Department of Gastroenterology and Hepatology, Kochi Medical School, Kochi, Japan.
Shinji
S
Iwasaki
Department of Gastroenterology and Hepatology, Kochi Medical School, Kochi, Japan.
Toshiji
T
Saibara
Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Japan.
Waki
W
Hosoda
Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Japan.
Yasushi
Y
Yatabe
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D061765:Endoscopic Ultrasound-Guided Fine Needle Aspiration; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D018358:Neuroendocrine Tumors / Q000737:chemistry* / Q000473:pathology*; D010179:Pancreas / Q000737:chemistry* / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000737:chemistry* / Q000473:pathology*; D011237:Predictive Value of Tests; D012372:ROC Curve; D012189:Retrospective Studies; D015996:Survival Rate; D055815:Young Adult
D019394:Ki-67 Antigen