1158P - Ki-67 index variability in neuroendocrine tumors

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Neuroendocrine Tumours
Pathology/Molecular Biology
Basic Scientific Principles
Presenter Jeffrey Craig
Authors J. Craig1, M. Cheung2, C. Law3, S. Singh4
  • 1Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto/CA
  • 2Hematology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto/CA
  • 3Surgical Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto/CA
  • 4Medical Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto/CA



The Ki-67 labeling index is now well recognized as an integral factor in the identification and treatment of neuroendocrine tumors (NETs) from both a prognosis and treatment perspective. In 2010, the WHO endorsed a grading system of NETs dividing tumors into G1 (Ki-67 <3%), G2 (Ki-67 3-20%), and G3 (Ki-67 > 20%) classes. Previous studies have associated higher Ki-67 scores with greater morbidity, with G3 tumors behaving particularly aggressively, often requiring cytotoxic chemotherapy. Currently Ki-67 is determined from a single biopsy in a majority of cases. Little is known about the variability of the Ki-67 labeling index during the disease course or between primary and metastatic deposits, and there are no consensus guidelines on taking multiple biopsy specimens throughout the disease course. AIMS: To compare Ki-67 labeling among multiple biopsy samples in individual patients to examine for variability.


The Sunnybrook Odette NETs database (n = 327) was retrospectively reviewed for patients with a confirmed diagnosis of NET and multiple ( > = 2) biopsy or surgical pathologic specimens, either at variable times in their disease course or biopsies of both the primary and metastasis. All but 2 cases were reviewed by our expert local neuroendocrine pathologist. Changes in WHO classification between multiple specimens in individual patients were determined.


43 patients were identified for inclusion in the analysis. 39 patients had pathology on their primary tumor as well as a metastatic focus, while 4 had pathology on multiple metastatic foci only. 16/43 patients (37.2%) were identified who had enough variability between Ki-67 indices resulting in differing WHO classification grades. Twelve cases of 43 (27.9%) resulted in a second sample that increased the WHO grade by at least one level. Seven of 43 (16.3%) resulted in a new WHO classification of G3.


The Ki67 labeling index in neuroendocrine tumors may change throughout the disease course, may differ between primary tumor and metastases, and may behave more aggressively later in the disease. Given the reliance on this index for management decisions, multiple biopsies of both the primary and metastatic tumor as well as through the disease course may be required to effectively treat these heterogeneous malignancies.


All authors have declared no conflicts of interest.