The Ki-67 labeling index and lymphatic/venous permeation predict the metastatic potential of rectal neuroendocrine tumors

Endoscopic resection has been used to treat small rectal neuroendocrine tumors (NETs). However, the indication for additional surgery after endoscopic resection is unclear. The aim of this study was to identify risk factors for rectal NET metastasis and to determine the indication for additional surgery. Fifty-five patients with a total of 57 rectal NETs, treated between October 2003 and January 2013, were retrospectively divided into metastatic (11 lesions) and non-metastatic (46 lesions) groups. Tumor size, central depression, invasion depth, lymphatic and venous permeation, mitotic activity, nuclear abnormality, Ki-67 labeling index, and World Health Organization grading classification (G1 or G2) were compared between the groups. Patients underwent endoscopic submucosal resection with a ligation device, transanal full-thickness surgical resection, or radical surgery. By univariate analysis, the odds ratios (OR) for a Ki-67 labeling index > 3.0 %, positive lymphatic or venous permeation, World Health Organization grading classification G2, tumor size > 10 mm, submucosal invasion > 4000 mu m, and central depression were 120 (P < 0.001), 67.6 (P < 0.001), 58.7 (P < 0.001), 9.8 (P = 0.0037), 6.8 (P = 0.012), and 5.7 (P = 0.018), respectively. Multivariate logistic regression analyses showed that vascular permeation (OR 111; P = 0.006) and a Ki-67 labeling index > 3.0 % (OR 88; P = 0.012) were independent risk factors for metastasis. The Ki-67 labeling index and lymphatic/venous permeation were reliable predictors of rectal NET metastases.