Low Ki-67 linked to shorter disease-free survival in non-metastatic colorectal cancer

Patients with non-metastatic colorectal adenocarcinoma whose tumours show low Ki-67 expression may face a significantly shorter disease-free survival than those with high expression, according to a retrospective cohort study published in the journal Diagnostic Pathology. The finding, based on 207 cases, adds to a long-running debate over whether this widely used proliferation marker carries prognostic weight in colorectal cancer, where its significance has remained uncertain despite an established role in several other tumour types.

Ki-67 is a cellular proliferation marker that pathologists use to gauge how actively tumour cells are dividing. In the new study, a team led by Ángel Romo-Navarro and Juan Ruiz-Martín assessed its prognostic value in an independent retrospective cohort of patients with non-metastatic colorectal adenocarcinoma, analysing both overall survival and disease-free survival.

The researchers divided the cohort according to the proportion of tumour cells staining positive for Ki-67, using a cut-off of 50 percent. Of the 207 cases, 132, or 63.8 percent, showed high Ki-67 expression of 50 percent or more, while 75 cases, or 36.2 percent, showed low expression below that threshold.

Using Kaplan–Meier survival analysis, the team found no significant difference in overall survival according to Ki-67 status, with a p-value of 0.158. Disease-free survival, however, did differ significantly between the two groups, with a p-value of 0.032.

The magnitude of the disease-free survival difference was substantial over long-term follow-up. Fifteen-year disease-free survival was 59 percent in the high Ki-67 group compared with 46 percent in the low Ki-67 group, meaning that patients whose tumours expressed the marker at lower levels fared worse over that period.

The association was examined further using Cox proportional hazards regression, both in the overall cohort and stratified according to adjuvant therapy. In the stratified multivariable analysis, higher Ki-67 was significantly associated with a lower hazard of a disease-free survival event among patients who received adjuvant therapy. Each one-percentage-point increase in Ki-67 corresponded to a hazard ratio of 0.954, with a 95 percent confidence interval of 0.925 to 0.984 and a p-value of 0.003.

On the basis of these results, the authors conclude that in patients with non-metastatic colorectal adenocarcinoma receiving conventional adjuvant therapy, low Ki-67, defined as below 50 percent, may identify a subgroup with significantly shorter disease-free survival. The association was reported specifically for the adjuvant-treated stratum in the multivariable model, and no significant overall survival difference was observed in the Kaplan–Meier analysis.

The study is a retrospective cohort analysis, and its conclusions are framed accordingly. The published version notes that the article is being shared early to provide faster access to peer-reviewed, accepted research; it is citable and carries a permanent DOI, but this version is subject to further edits and will be replaced by the final Version of Record.

Because the prognostic significance of Ki-67 in colorectal cancer has remained uncertain, the authors describe their work as an assessment in an independent retrospective cohort. The results suggest that, at least among patients receiving conventional adjuvant therapy, proliferation status as measured by Ki-67 may help distinguish patients at higher risk of disease recurrence, while its role in overall survival in this cohort was not statistically significant.

Subject of Research: The prognostic value of Ki-67 expression for survival outcomes in non-metastatic colorectal adenocarcinoma.

Article Title: Prognostic value of Ki-67 in non-metastatic colorectal adenocarcinoma: a retrospective study

Article References: Romo-Navarro, Á., Gutiérrez, I. G.-C., Amo-Salas, M., Parra-Tercero, A. R., Recuero-Pradillo, M., Sánchez-Muñoz, C., Lázaro, C. M. M., López, E. C., Simón, R. S., Quimbayo-Arcila, C., Martín, Y. H., Ruiz, L. H., Campos-Martín, Y., & Ruiz-Martín, J. (2026). Prognostic value of Ki-67 in non-metastatic colorectal adenocarcinoma: a retrospective study. Diagnostic Pathology. https://doi.org/10.1186/s13000-026-01863-y

Image Credits: AI Generated

DOI: 10.1186/s13000-026-01863-y

Keywords: Ki-67, colorectal adenocarcinoma, disease-free survival, overall survival, prognostic marker, retrospective study, adjuvant therapy, Cox regression, Kaplan-Meier analysis, proliferation marker, Diagnostic Pathology, Prognostic