title: Liver metastases of small intestine neuroendocrine tumors: Ki-67 heterogeneity and World Health Organization grade discordance with primary tumors.
abstract: OBJECTIVE
  We examined Ki-67 heterogeneity within single and between synchronous liver metastases of small intestine neuroendocrine tumors.
  
  
  METHODS
  There were 27 patients (10 men and 17 women) with two or more liver metastases. The Ki-67 index was used to classify the tumors into World Health Organization grade 1, 2, or 3. The association between Ki-67 heterogeneity and tumor size of liver metastases was analyzed. Correlation of tumor grade with patient survival was also evaluated.
  
  
  RESULTS
  Primary tumors from 20 patients were graded, including 17 grade 1 and three grade 2. A total of 188 liver metastases were resected, including 122 (65%) grade 1, 47 (25%) grade 2, and 19 (10%) grade 3. The highest tumor grade was grade 1 in 10 (37%), grade 2 in nine (33%), and grade 3 in eight (30%) patients. Patients with one or more grade 3 liver lesions had a shorter progression-free survival compared with those with grade 1/2 tumors (P < .001). A positive association was found between tumor size and Ki-67 index (P = .04), as well as between tumor size and intratumoral Ki-67 heterogeneity (P < .001).
  
  
  CONCLUSIONS
  Intratumoral and intertumoral Ki-67 heterogeneity is common and positively correlated with tumor size. The presence of one or more grade 3 liver lesions predicts a worse prognosis.
authors.affiliation: From the Departments of Pathology, Microbiology and Immunology, Chanjuan.Shi@vanderbilt.edu.
authors.forename: Chanjuan
authors.initials: C
authors.lastname: Shi
authors.affiliation: From the Departments of Pathology, Microbiology and Immunology.
authors.forename: Raul S
authors.initials: RS
authors.lastname: Gonzalez
authors.affiliation: Biostatistics.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Biostatistics.
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Koyama
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore, MD; and.
authors.forename: Toby C
authors.initials: TC
authors.lastname: Cornish
authors.affiliation: Hematology/Oncology, and.
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Hande
authors.affiliation: Clinical Radiology and Radiological Sciences, and VA Tennessee Valley Healthcare System, Nashville.
authors.forename: Ronald
authors.initials: R
authors.lastname: Walker
authors.affiliation: Clinical Radiology and Radiological Sciences, and.
authors.forename: Martin
authors.initials: M
authors.lastname: Sandler
authors.affiliation: Hematology/Oncology, and.
authors.forename: Jordan
authors.initials: J
authors.lastname: Berlin
authors.affiliation: Neuroendocrine Surgery, Surgical Oncology, Vanderbilt University Medical Center, Nashville, TN;
authors.forename: Eric H
authors.initials: EH
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D003710:Demography; D018450:Disease Progression; D018572:Disease-Free Survival; D004502:Education, Medical, Continuing; D005260:Female; D006801:Humans; D007414:Intestinal Neoplasms / Q000145:classification / Q000401:mortality / Q000473:pathology*; D007421:Intestine, Small / Q000473:pathology; D019394:Ki-67 Antigen / Q000378:metabolism*; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000145:classification / Q000401:mortality / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D018358:Neuroendocrine Tumors / Q000145:classification / Q000401:mortality / Q000556:secondary*; D011379:Prognosis; D014944:World Health Organization; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen
keywords: Liver metastasis; Small intestine; Tumor heterogeneity; Well-differentiated neuroendocrine tumor