Grades and the Ki-67 index

The grade of a large bowel or rectal neuroendocrine tumour (NET) tells you how much the cancer cells look like normal cells under a microscope. It gives your doctor an idea of how the tumour might behave and whether it is likely to spread. 

There are different ways to grade NETs. In the UK, doctors use a system created by the World Health Organisation (WHO). The WHO grading system divides NETs into 3 groups:

  • grade 1 (NET G1 or WHO 1)
  • grade 2 (NET G2 or WHO 2)
  • grade 3 (neuroendocrine carcinoma, NEC or WHO 3)

Grade 1

The cells look very like normal cells. Tumours are usually slow growing and less likely to spread. They are also called low grade or well differentiated tumours.

Grade 2

The cells look less like normal cells and are more likely to grow and spread. They are also called moderately differentiated tumours.

Grade 3

The cells look very abnormal. They tend to grow quickly and are more likely to spread.

Grade 3 is also called poorly differentiated neuroendocrine carcinoma (NEC).

Ki–67 index test

The Ki-67 or mitotic index are ways of describing how many cells are dividing. A specialist doctor (pathologist) counts the number of NEN cells that have started to divide into 2 new cells (mitoses) under a microscope. And a special stain measures the Ki-67 value.

Diagram of Ki 67

Your doctor might tell you the number of cells that are dividing (number of mitoses), or you may see this on your pathology report. This helps your doctor decide which treatment you need.

Ki-67 index of 2% or lower

A Ki-67 index of 2% or lower means that fewer than 2 in every 100 cells (2%) are dividing. This is a grade 1 NET (WD NET G1).

Ki-67 index between 3% and 20%

This means that between 3 and 20 cells in every 100 cells (3% and 20%) are dividing. This is a grade 2 NET (WD NET G2).

Ki-67 index higher than 20%

A Ki-67 index of more than 20% means that more than 2 in every 10 cells (20%) are dividing. This is either a grade 3 NET (WD NET G3) or a neuroendocrine carcinoma (PD NEC G3). 

Treatment

The grade of your cancer helps your doctor decide which treatment you need. Treatment also depends on:

  • where the cancer is and whether it has spread
  • other health conditions you may have
  • Gastroenteropancreatic neuroendocrine neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
    M. Pavel and others
    Annals of Oncology 2020, Vol 31, Issue 5 

  • Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs)
    J Ramage and others
    Gut, 2012. Vol 61, Pages 6-32

  • AJCC Cancer Staging Manual (8th edition)
    Mahul B. Amin and others
    Springer, 2017

  • ENETS consensus guidelines for the management of patients with digestive neuroendocrine neoplasms: colorectal neuroendocrine neoplasms
    M Caplin and others
    Neuroendocrinology, 2012. Vol. 95, Pages 88-97

Last reviewed: 
16 Jun 2021
Next review due: 
16 Jun 2024

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