Variability of Ki67 labeling index in multiple neuroendocrine tumor specimens over the course of the disease

Ki67- is a valid surrogate for biologic behavior of neuroendocrine tumors (NETs), with higher levels associated with aggressive behavior. The World Health Organization (WHO) classifies NETs according to Ki67 (G1: <3%; G2 : 3–20%; G3: >20%). Little is known about the evolution of NETs histologic characteristics over the disease course. This study examines variations in Ki67 throughout NETs disease course.

This was a retrospective single centre study reviewing cases from the Sunnybrook Odette Cancer Center NET database for patients with multiple pathology specimens. Primary outcome was the WHO NET class based on Ki67 for each specimen. We assessed change in WHO class between specimens.

Forty-three patients were retrieved, of which 39 had specimens from the primary tumor and a metastatic focus, and 4 had specimens from multiple metastatic foci. Sixteen (37.0%) were identified with Ki-67 falling in different WHO classes on distinct biopsies. For 12 (75.0%) of those 16 patients, Ki67 showed enough variability for WHO class to be upstaged: 5 (31%) from G1 to G2, 2 (13%) from G2 to G3, and 5 (31%) from G1 to G3.

This study demonstrates when multiple pathology specimens were available, Ki67 varied throughout NETs disease course, with a majority of cases upgraded to a higher WHO class. If confirmed, this finding may have implications in how neuroendocrine tumors are monitored and treated. Further research is warranted to confirm these findings, understand better the underlying mechanisms of Ki67 variability, and define its relationship to prognosis.

Source: Science Direct