Comparative Analysis of Amide Proton Transfer MRI and Diffusion-Weighted Imaging in Assessing p53 and Ki-67 Expression of Rectal Adenocarcinoma

Background: The evaluation of prognostic factors in rectal carcinoma patients has important clinical significance. P53 status and the Ki-67 index have served as prognostic factors in rectal carcinoma. Amide proton transfer (APT) imaging has shown great potential in tumor diagnosis. However, few studies reported the value of APT imaging in evaluating p53 and Ki-67 status of rectal carcinoma.

Purpose: To investigate the feasibility of amide proton transfer MRI in assessing p53 and Ki-67 expression of rectal adenocarcinoma, and compare it with conventional diffusion-weighted imaging (DWI).

Study type: Retrospective.

Population: Forty-three patients with rectal adenocarcinoma (age: 34-85 years).

Field strength/sequence: 3T/APT imaging using a 3D turbo spin echo (TSE)-Dixon pulse sequence with chemical shift-selective fat suppression, 2D DWI, and 2D T₂ -weighted TSE.

Assessment: Mean tumor APT signal intensity (SI_mean ) and apparent diffusion coefficient (ADC_mean ) were measured. Traditional tumor pathological analysis included WHO grades, pT (pathologic tumor) stages, and pN (pathologic node) stages. Expression levels of p53 and Ki-67 were determined by immunohistochemical assay.

Statistical tests: One-way analysis of variance (ANOVA); Student's t-test; Spearman's correlation coefficient; receiver operating characteristic (ROC) curve analysis.

Results: High-grade tumors, more advanced stage tumors, and tumors with lymph node involvement had higher APT SI_mean values: high grade (n = 15) vs. low-grade (n = 28), P < 0.001; pT2 (n = 10) vs. pT3 (n = 20) vs. pT4 (N = 13), P = 0.021; pN0 (n = 24) vs. pN1-2 (n = 19), P = 0.019. ADC_mean differences were found in tumors with different pT stage: pT2 (n = 10) vs. pT3 (n = 20) vs. pT4 (N = 13), P = 0.013, but not in tumors with different histologic grade: high grade (n = 15) vs. low-grade (n = 28), P = 0.3536; or pN stage: pN0 (n = 24) vs. pN1-2 (n = 19), P = 0.624. Tumor with p53 positive status had higher APT SI_mean than tumor with negative p53 status (2.363 ± 0.457 vs. 2.0150 ± 0.3552, P = 0.014). There was no difference in ADC_mean with p53 status (1.058 ± 0.1163 10^-3 mm² /s vs. 1.055 ± 0.128 10^-3 mm² /s, P = 0.935). APT SI_mean and ADC_mean were significantly different in tumors with low and high Ki-67 status (1.7882 ± 0.11386 vs. 2.3975 ± 0.41586, P < 0.001; 1.1741 ± 0.093 10^-3 mm² /s vs. 1.0157 ± 0.10459 10^-3 mm² /s, P < 0.001, respectively). APT SI_mean exhibited a positive correlation with p53 labeling index and Ki-67 labeling index (r = 0.3741, P = 0.0135; r = 0.7048; P < 0.001, respectively). ADC_mean showed no correlation with p53 labeling index, but a negative correlation with Ki-67 labeling index (r = -0.5543, P < 0.0001). ROC curves demonstrated that APT SI_mean had significantly higher diagnostic ability for differentiation of high Ki-67 expression of rectal adenocarcinoma than ADC_mean (81.2% vs. 78.12%, 90.91% vs. 63.64; P < 0.001 vs. P = 0.017), while no difference was found in predicting p53 status (92.86% vs. 71.4%, 53.33% vs. 66.7%; P < 0.001 vs. P = 0.0471).

Data conclusion: APT SI_mean was related to p53 and Ki-67 expression levels in rectal adenocarcinoma. APT imaging may serve as a noninvasive biomarker for assessing genetic prognostic factors of rectal adenocarcinoma.

Level of evidence: 3 TECHNICAL EFFICACY STAGE: 2.