Ki-67 Antigen, as a core marker of cell proliferation, has a direct positive correlation with the proliferation activity of tumor cells in terms of its expression level. In clinicopathological assessment, the Ki-67 labeling index (i.e., the percentage of positive tumor cells) is usually detected by immunohistochemical techniques. For every 10% increase in this index, it often indicates that the tumor proliferation rate rises by approximately 1.5 times. For instance, in invasive ductal carcinoma of the breast, A Ki-67 index lower than 15% is usually classified as Luminal A type, with a five-year survival rate of up to 92%. However, for patients with triple-negative breast cancer whose index exceeds 30%, the five-year survival rate may drop below 76%. According to the statistical analysis of more than 10,000 samples by the International Breast Cancer Research Group (IBCSG) in 2019, for every 20% increase in the Ki-67 index, the risk of tumor recurrence increases by 33% (HR=1.33, 95% CI: 1.25-1.41).
In the grading of neuroendocrine tumors, the quantitative analysis of Ki-67 Antigen directly determines the WHO grading criteria. The Ki-67 index of grade G1 tumors is ≤2%, that of grade G2 is 3%-20%, and that of grade G3 is > 20%. Studies have shown that the median survival period for patients with grade G1 pancreatic neuroendocrine tumors exceeds 10 years, while for those with grade G3 tumors, it is only slightly above 14 months. A multicenter study in The Lancet Oncology in 2020 showed that the classification system based on the Ki-67 index was highly correlated with the treatment response rate: the treatment response rate of G2 grade patients to everolimus was approximately 35%, while that of G3 grade patients dropped sharply to 12%.
The standardization of the detection of this antigen is crucial for clinical consistency. When using the RP215 monoclonal antibody developed by Roche Biotech for detection, the thickness of the tissue section should be controlled at 4μm, the pH value of the antigen retrieval solution should be maintained at 9.0±0.5, and the incubation time should be strictly controlled at 60±5 minutes. If the operational deviation exceeds this range, it may lead to a 15% to 20% increase in the false positive rate. According to the inter-laboratory quality assessment data of the American College of Pathologists (CAP), the standardized process can reduce the coefficient of variation of inter-laboratory Ki-67 test results from 25% to within 8%.
With the development of digital pathology, quantitative analysis of Ki-67 assisted by artificial intelligence is becoming a new trend. The AIScanner system developed by Deep Thinking Medical has an accuracy rate of 97.3% in identifying Ki-67 positive cells, with an analysis speed 50 times faster than manual counting and a processing time of only 120 seconds for a single slice. In 2022, a multi-center trial led by Peking Union Medical College Hospital confirmed that the AI system reduced the inter-observer variance assessed by Ki-67 from 18.7% in traditional methods to 3.5%, significantly improving the accuracy of risk stratification for gastrointestinal stromal tumors.
Current international guidelines strongly recommend incorporating Ki-67 Antigen testing into the routine diagnostic pathways for various tumors. The NCCN guidelines clearly state that for well-differentiated pancreatic neuroendocrine tumors, adjuvant chemotherapy should be considered when the Ki-67 index is > 10%. Data from Memorial Sloan Kettering Cancer Center indicated that the adjustment of treatment strategies based on the Ki-67 index extended the median progression-free survival of patients with grade G3 neuroendocrine tumors from 5.2 months to 11.7 months. With the development of liquid biopsy technology, the detection sensitivity of Ki-67 expression level in circulating tumor cells in peripheral blood has reached 0.01%, providing a new solution for dynamic monitoring of treatment response.