Journal
AMERICAN JOURNAL OF CLINICAL PATHOLOGY
Volume 143, Issue 3, Pages 398-404Publisher
OXFORD UNIV PRESS INC
DOI: 10.1309/AJCPQ55SKOCYFZHN
Keywords
Tumor heterogeneity; Small intestine; Well-differentiated neuroendocrine tumor; Liver metastasis
Categories
Funding
- National Institutes of Health (NIH)/National Institute of Diabetes and Digestive and Kidney Diseases [P30DK058404]
- NIH [NCIP50CA095103]
- NIH/National Cancer Institute [K12 CA90625]
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Objectives: 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 class in, 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 I 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.
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