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PubMed This is a summary of 22 peer-reviewed journal articles Updated
Oncology · Neuroendocrine Tumor

What is the Ki-67 Index in Neuroendocrine Tumors (NETs)?

At a Glance

The Ki-67 index measures how quickly neuroendocrine tumor (NET) cells are dividing, expressed as a percentage. A lower score (under 3%) indicates a slow-growing Grade 1 tumor, while a score over 20% indicates an aggressive Grade 3 tumor, directly guiding your treatment options.

In this answer

3 sections

01

How the Ki-67 Index is Calculated

02

Tumor Grades and the Ki-67 Cutoffs

03

How Your Ki-67 Index Guides Treatment Choices

The Ki-67 index is a measurement of how fast your tumor cells are dividing and multiplying. When you read your pathology report for a neuroendocrine tumor (NET), you will likely see this index listed as a percentage. This number is one of the most important pieces of information for determining your prognosis. A lower percentage indicates that the tumor is slow-growing, while a higher percentage means the tumor is growing quickly and behaving more aggressively [1][2].

How the Ki-67 Index is Calculated

To calculate this number, a pathologist takes a sample of your tumor tissue—gathered from a biopsy or surgery—and treats it with a special chemical stain [3]. This stain highlights the cells that are actively in the process of dividing. The pathologist then counts these dividing cells, either manually under a microscope or by using digital image analysis [4][5].

If your Ki-67 index is 5%, it means that out of 100 tumor cells, 5 of them are actively dividing [6]. Because cell division can vary across different areas of a tumor, pathologists specifically search the tissue sample for hotspots—the areas with the highest amount of cell division—to calculate your final, most accurate percentage [3].

Tumor Grades and the Ki-67 Cutoffs

The World Health Organization (WHO) uses the Ki-67 index, along with your tumor’s mitotic count, to assign a grade to your tumor [7][8]. The mitotic count is another way of measuring cell division, often written on your report as a specific number of dividing cells in a small area (like “per 2mm²”) [7]. If your Ki-67 index and mitotic count point to two different grades, doctors will typically assign the higher of the two grades to ensure you receive adequate treatment [8].

For the most common types of NETs—gastroenteropancreatic tumors found in the stomach, intestine, and pancreas—the grades are divided as follows:

  • Grade 1 (G1): Very slow-growing tumors. The Ki-67 index is less than 3% [7][9].
  • Grade 2 (G2): Intermediate-grade tumors that grow slightly faster. The Ki-67 index is from exactly 3% up to 20% [7][10].
  • Grade 3 (G3): Fast-growing, aggressive tumors with a Ki-67 index greater than 20% [10][11].

(Note: If your tumor is in your lung, you may instead see terms like “typical carcinoid” or “atypical carcinoid.” Lung NETs use a slightly different grading system, though the Ki-67 index is still used to help distinguish them from more aggressive cancers [12].)

When looking at the cells, pathologists also evaluate if the tumor is well-differentiated (the cells look somewhat like healthy, normal cells) or poorly differentiated (the cells look highly abnormal and disorganized) [13][14].

Poorly differentiated tumors are medically classified as neuroendocrine carcinomas (NECs) [13]. It is important to know this distinction because you can have a Grade 3 well-differentiated neuroendocrine tumor, which behaves differently and requires completely different treatments than a Grade 3 poorly differentiated neuroendocrine carcinoma [10][15].

How Your Ki-67 Index Guides Treatment Choices

Because the Ki-67 percentage reveals the speed of tumor growth, it heavily influences your treatment options [16][17].

  • Lower Ki-67 (G1 and some G2 tumors): Because these tumor cells divide very slowly, traditional chemotherapy is often less effective. Instead, your care team may recommend active surveillance, surgical removal, or medications called somatostatin analogs (SSAs), which are drugs that help control hormone symptoms and slow down tumor growth [16][18].
  • Higher Ki-67 (G3 tumors): Fast-growing tumors require more intensive approaches. If you have a well-differentiated G3 tumor, treatments might include targeted therapies or peptide receptor radionuclide therapy (PRRT, a type of targeted radiation) [10][19]. However, if your report indicates a poorly differentiated neuroendocrine carcinoma (NEC), platinum-based chemotherapy is typically the standard treatment [19][13].

The Ki-67 index is not always permanent. It can sometimes change over time or vary between the original tumor and areas where the tumor has spread [20][21]. If your tumor begins to behave differently or grow in new areas, your doctor might recommend a new biopsy to recheck the Ki-67 index and adjust your care plan accordingly [22].

Common questions in this guide

What does the Ki-67 index measure in neuroendocrine tumors?
The Ki-67 index is a percentage that shows how fast your tumor cells are actively dividing and multiplying. A lower percentage indicates a slow-growing tumor, while a higher percentage means the tumor is growing quickly and behaving more aggressively.
What is the difference between a Grade 1, Grade 2, and Grade 3 NET?
Tumors are graded based on the Ki-67 index and mitotic count. Grade 1 tumors are slow-growing with a Ki-67 under 3%. Grade 2 tumors have a score between 3% and 20%, while Grade 3 tumors are fast-growing with a Ki-67 higher than 20%.
What does it mean if my pathology report says poorly differentiated?
A poorly differentiated tumor means the cells look highly abnormal and disorganized under a microscope. These are classified as neuroendocrine carcinomas (NECs) and usually require different, more aggressive treatments than well-differentiated tumors.
How does my Ki-67 score impact my treatment plan?
Slower-growing tumors with a low Ki-67 are often managed with surgery, surveillance, or somatostatin analogs. Faster-growing tumors with a high Ki-67 typically require targeted therapies, peptide receptor radionuclide therapy (PRRT), or chemotherapy.
Can my Ki-67 index change over time?
Yes, the Ki-67 percentage can change as a tumor evolves or if it spreads to new areas. If your tumor begins to behave differently, your doctor may recommend a new biopsy to recheck the index and adjust your treatment plan.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.What is the exact Ki-67 percentage and mitotic count listed on my pathology report?
  2. 2.Does my report indicate that my tumor is well-differentiated or poorly differentiated?
  3. 3.Are there any mentions of 'hotspots' in my biopsy, and did the pathologist take samples from multiple areas?
  4. 4.Based on my Ki-67 index and tumor grade, am I a better candidate for targeted therapies like PRRT, or traditional chemotherapy?
  5. 5.Will my Ki-67 index need to be retested if my tumor grows or if new metastases appear?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

Related questions

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References

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This page explains the Ki-67 index and neuroendocrine tumor pathology terminology for educational purposes. Your oncologist and pathologist are the best sources for interpreting your specific pathology report.

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