Magnetic resonance imaging R2* mapping for evaluating Ki-67 proliferation index and cytokeratin 19 expression in...

Iron may be involved in the occurrence and development of hepatocellular carcinoma (HCC), and R2* relaxometry is the preferred noninvasive method for iron quantification. However, whether hepatic and intratumoral R2* values are associated with Ki-67 proliferation index (PI) and cytokeratin 19 (CK19) expression in iron-sparing HCC remains unclear. This study aimed to determine the associations of preoperative hepatic and intratumoral R2* values with Ki-67 PI and CK19 expression in patients with solitary iron-sparing HCC.

Consecutive adult patients with solitary HCC who underwent surgery at a single center between May 2018 and May 2025 were retrospectively enrolled. All patients had intratumoral iron-sparing as indicated on preoperative 3.0-T magnetic resonance imaging (MRI) R2* imaging and had complete postoperative pathological data for Ki-67 and CK19 expression. Hepatic and intratumoral R2* values were measured via region of interest (ROI) analysis. According to the cohort median, a high Ki-67 PI was defined as Ki-67 positivity in >20% of tumor cells, and CK19 positivity was defined membranous/cytoplasmic staining in ≥5% of tumor cells. Meanwhile, hepatic R2* was categorized at a cutoff of 136 s^-1 and alpha-fetoprotein (AFP) at a cutoff of 400 ng/mL. Exact logistic regression identified predictors of a high Ki-67 PI and positive CK19 expression, and model performance was evaluated via the area under the receiver operating characteristic curve (AUC).

Eighty patients were enrolled (mean age 55.11±9.69 years; 93.75% male). A high Ki-67 PI was present in 43 (53.75%) patients, and positive CK19 expression was present in 16 (20.00%) patients. The high Ki-67 PI group, as compared to the low Ki-67 PI group, had higher AFP levels (P=0.035) and lower hepatic R2* values (P=0.038). According to multivariate exact logistic analysis, the independent predictors of a high Ki-67 PI were AFP >400 ng/mL [odds ratio (OR) =19.04; 95% confidence interval (CI): 2.98-121.46, P=0.002] and a hepatic R2* value ≥136 s^-1 (OR =0.27; 95% CI: 0.10-0.75; P=0.012); the model including both of these factors yielded an AUC of 0.771 (95% CI: 0.664-0.858). The only independent predictor of positive CK19 expression was AFP >400 ng/mL (OR =8.50; 95% CI: 2.38-30.34; P=0.001), while an R2* value ≥136 s^-1 was not significantly associated with positive CK19 expression (P=0.124).

In this retrospective single-center study of patients with solitary iron-sparing HCC, it was found that a combination of hepatic R2* (≥136 s^-1) and AFP (>400 ng/mL) values may serve as a biomarker for predicting a high Ki-67 PI, whereas they had limited value for predicting positive CK19 expression.