Tumor-associated macrophages are a useful biomarker to predict recurrence after surgical resection of nonfunctional pancreatic neuroendocrine tumors.
OBJECTIVE
Patients with nonfunctional pancreatic neuroendocrine tumors (NF-PNETs) have poorer survival than those with functional PNETs. Our objective was to identify risk factors for recurrence after resection to better define surveillance parameters to improve long-term outcomes.


METHODS
A retrospective analysis was performed for NF-PNET patients who underwent resection at the University of Michigan from 1995 to 2012. Immunohistochemical staining of tissues from patients with and without disease recurrence was performed for Ki-67 and the macrophage marker CD68, as tumor-associated macrophages are important for PNET development and progression. Clinicopathological factors and patient outcomes were measured.


RESULTS
Ninety-seven NF-PNET patients underwent surgical resection. There was a recurrence rate of 14.4% (14/97). The median time to recurrence was 0.61 years, with 10 (71%) patients recurring within the first 2 years. Six of 7 patients (86%) monitored at 6-month surveillance intervals were diagnosed with recurrence on their first computed tomographic scan or during the intervening intervals. By Cox proportional hazards analysis, the most significant independent risk factors for recurrence were higher grade, stage, and intraoperative blood loss. High CD68 score and Ki-67 index correlated with recurrence risk, and Ki-67 index inversely correlated with time to recurrence. In patients who otherwise had few risk factors, a high CD68 score was a significant prognostic factor for recurrence.


CONCLUSIONS
In patients with NF-PNETs, risk factors associated with recurrence were high EBL, grade, stage, CD68 score, and Ki-67 index. The CD68 score was an important prognostic factor in patients who otherwise had few clinicopathological risk factors; therefore, the CD68 score should be considered when planning surveillance strategies. We recommend that NF-PNET patients at high risk of recurrence undergo initial surveillance every 3 months for 2 years after surgery.
Departments of *Surgery †Pathology ‡Molecular and Integrative Physiology §Translational Oncology Program, University of Michigan Medical Center, Ann Arbor, MI.
Iris H
IH
Wei
Charles M
CM
Harmon
Massimo
M
Arcerito
Debbie F
DF
Cheng
Rebecca M
RM
Minter
Diane M
DM
Simeone
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002760:Cholangiopancreatography, Endoscopic Retrograde; D019160:Endosonography; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D015994:Incidence; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000453:epidemiology / Q000378:metabolism; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000601:surgery; D011379:Prognosis; D012189:Retrospective Studies; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D014481:United States / Q000453:epidemiology; D055815:Young Adult
D014408:Biomarkers, Tumor