Role of Ki67 expression as a prognostic marker in advanced colorectal cancer

Colorectal cancer (CRC) is one of the most frequent malignancies and the third cause of death from cancer globally. To increase prognosis prediction in patients with CRC, understanding prognostic marker is crucial, especially in patient with advanced stages. Several studies have reported the prognostic value of the Ki67 expression in patient with cancer. However, only few studies on the prognostic role of Ki67 in CRC exist, and have partially shown contradictory results. The aim of this study is to compare Ki67 expression with clinicopathological and molecular parameters and to correlate Ki67 expression with CRC patients’ outcome.

52 formalin-fixed and paraffin-embedded colorectal tumor specimens and their corresponding reports and fellow-up were studied. Clinical and histological data were collected from the reports. The immunohistochemical study was performed using the anti-Ki-67 antibody. KRAS status was performed using the fully automated IdyllaTM KRAS Mutation Test. For statistical analyses, the staining results were categorized into two groups (weak & high) according to the percentage of Ki67-positive tumor cells as follows: low Ki67, 0%–25% & high Ki67, 25% and more. Statistical calculations were performed with SPSS software.

Ki67 was considered low in 48% and high in 52% of 52 interpretable CRCs. Using Ki67 expression as a continuous variable (ANOVA test), Ki67 expression was associated with nodal status (p=0.007), and with mutated KRAS status (p=0.029) but not with tumor grade, histological tumor type or tumor localization. Multivariable analysis by Cox regression showed that Ki67 high expression together with the histological grade, tumor stage and the number of chemotherapy lines were all independently prognosis predictors of patients with CRC (p=0.05).

In summary, our data show that high Ki67 expression in CRCs is associated with good clinical outcome. High Ki67 seems to be linked to CRC clinicopathological parameters and to the proliferation molecular pathway RAS/MAPK and indicates a cellular state of high proliferative activity. Finally, our findings argue for a clinical utility of Ki67 immunostaining as an independent prognostic biomarker in CRC and as a prediction marker for response to chemotherapy.

The authors.

Has not received any funding.

All authors have declared no conflicts of interest.