Grading neuroendocrine tumours (NETs) is crucial in understanding the behaviour and prognosis of these complex cancers. Among the various factors used for grading, the Ki-67 proliferation index stands out as a significant marker.
This article explains:
Neuroendocrine Cancer Australia (NECA), is dedicated to supporting individuals diagnosed with NETs, and their families. NECA offers a wealth of resources, educational programs, and advocacy efforts aimed at deepening the understanding of NETs, improving patient care, and encouraging research advancements. Patients diagnosed with NETs can engage with NECA’s comprehensive support and information by calling the NET nurse line.
Grading plays a fundamental role in the management of neuroendocrine tumours. It helps classify NETs based on how quickly the tumour cells are dividing and growing. This classification is essential for predicting tumour aggressiveness and guiding treatment strategies. The higher the grade, the more aggressive the tumour is likely to be, and the more intense the treatment may need to be.
NET grading provides valuable insights into how a tumour is likely to behave. By assessing how rapidly cancer cells are proliferating, doctors can predict the likely course of the disease and decide on the most appropriate interventions.
While both grading and staging are used to describe cancer, they refer to different aspects.
Both grading and staging are important for a comprehensive understanding of NETs, but they serve distinct purposes in diagnosis and treatment planning.
The Ki-67 protein is a cellular marker used to assess the rate of cell proliferation. It is present in cells that are actively dividing but absent in resting (non-dividing) cells.
The Ki-67 index reflects how many cells in a tumour sample are in the process of dividing, providing a snapshot of the tumour’s growth rate.
To determine the Ki-67 index, pathologists use immunohistochemistry techniques to stain tumour tissue samples. This staining highlights the cells that express the Ki-67 protein, allowing for an accurate count of proliferating cells. The result is expressed as a percentage, representing the proportion of tumour cells that are actively dividing.
The Ki-67 index is a key factor in grading NETs, which are classified into three grades based on their proliferation rates:
The grade influences treatment decisions, with higher-grade tumours often requiring more aggressive therapies.
There is a clear relationship between Ki-67 levels and the aggressiveness of a neuroendocrine tumour. Higher Ki-67 percentages are associated with a greater likelihood of rapid disease progression and metastasis.
As a result, understanding the Ki-67 index is essential for predicting patient outcomes and planning the appropriate level of intervention.
In addition to the Ki-67 index, the mitotic index is another factor used to assess tumour proliferation. The mitotic index measures the number of cells undergoing division in a specific area of the tumour.
While both factors are important for grading, the Ki-67 index is often more reliable for predicting tumour behaviour, especially when used alongside other indicators.
The process of measuring the Ki-67 index begins with a biopsy of the tumour tissue. Immunohistochemistry techniques are used to stain the sample.
The stained cells are then examined under a microscope and categorised for calculation, ready to provide an estimate of the tumour’s proliferation rate..
Pathologists calculate the Ki-67 index by counting the number of Ki-67 positive cells in a representative area of the tumour.
The percentage is determined by dividing the number of stained cells by the total number of cells observed.
One of the main challenges with the Ki-67 index is the lack of standardisation in how it is measured. Differences in staining techniques, counting methods, and interpretation can lead to variability in results.
The Ki-67 index has a significant impact on treatment decisions for NET patients. It has a range of prognostic implications, and can be used to more effectively understand the mysterious nature of high-grade NETs.
The Ki-67 can guide which treatments and therapies a patient receives.
The Ki-67 index helps tailor the treatment approach to the tumour’s aggressiveness, maximising effectiveness while minimising unnecessary side effects.
Aggressive, high-grade neuroendocrine carcinomas often have Ki-67 levels above 20%, indicating a high proliferation rate.
For these patients, the index helps guide the choice of aggressive treatments and plays a role in monitoring treatment response.
Like many diagnostic tools in the field of NET, the Ki-67 index has a range of limitations and challenges.
One limitation of the Ki-67 index is tumour heterogeneity. Different areas of the same tumour may have varying proliferation rates, which can complicate the assessment. A single biopsy may not capture the full extent of this variability, leading to potential inaccuracies in grading.
Variability in how the Ki-67 index is measured and interpreted can also lead to inconsistent results. Differences in staining protocols, equipment, and pathologist experience contribute to this issue. These inconsistencies can be overcome with more standardised methods to deliver accurate and reliable grading.
Despite its limitations, the Ki-67 index remains a valuable prognostic tool when used alongside other indicators, such as the mitotic index and imaging findings. Together, these factors provide a more complete picture of the tumour’s behaviour and help refine treatment strategies.
Efforts to standardise Ki-67 testing are underway, with researchers and organisations working to establish consistent guidelines for measurement and interpretation. These advancements aim to reduce variability and improve the reliability of the index as a prognostic tool.
New technologies are being developed to improve the accuracy of proliferation measurements. Digital pathology and artificial intelligence are being explored as ways to automate the counting of Ki-67 positive cells, potentially reducing human error and increasing consistency. Liquid biopsy techniques that detect tumour DNA in the bloodstream are also showing promise, offering a less invasive way to monitor tumour proliferation.
While it has limitations, ongoing advancements in standardisation and technology continue to enhance the usefulness of Ki-67.
Further information and support for people diagnosed with NETs is available by calling the NECA NET nurse line.
