WHO's classification is based on Ki-67%, which is an immunohistochemical test of tumor tissue. The MIB-1 (Mindbomb homologue 1) antigen binds to the Ki-67% protein, which is expressed in cells undergoing division. This antigen stains the cell nucleus. Thus, dividing cell nuclei can be differentiated from non-dividing nuclei. Ki-67% expresses the percent of cells in the tumor which are stained or in the division phase. If Ki-67% is 5%, this means that 5% of the cells are undergoing mitosis.
Ki-67% may be different in different areas of the tumor and is often higher in metastasis cells than the primary tumor. The area with the highest Ki-67 (”hot spots”) in the primary tumor provide the basis for classification.
|WHO classification (2010)
|Ki-67% < 3%
||Low gradeneuroendocrine tumor
||Intermediate grade neuroendocrine carcinoma
|Ki-67% > 20%
||High grade neuroendocrine carcinoma
In the American database SEERS (Surveillance, Epidemiology and End Results), there is metastasis at the time of diagnosis in 21% of patients with well differentiated tumor, 30% with a moderately differentiated carcinoma, and 50% with a poorly differentiated carcinoma.