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

Abstract

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 (SImean) and apparent diffusion coefficient (ADCmean) 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 SImean 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. ADCmean 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 SImean than tumor with negative p53 status (2.363 ± 0.457 vs. 2.0150 ± 0.3552, P = 0.014). There was no difference in ADCmean with p53 status (1.058 ± 0.1163 10−3 mm2/s vs. 1.055 ± 0.128 10−3 mm2/s, P = 0.935). APT SImean and ADCmean 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 SImean 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). ADCmean 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 SImean had significantly higher diagnostic ability for differentiation of high Ki‐67 expression of rectal adenocarcinoma than ADCmean (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...

Investigation of Breast Cancer Microstructure and Microvasculature from Time-Dependent DWI and CEST in Correlation with Histological Biomarkers

“…Second, Ki-67 LI was calculated as the mean positive cell count in the cellular area, and it therefore could not be directly compared with the mean APT SI value, which was calculated from the ROI covering the whole tumor including necrosis. Although several previous studies have reported positive correlations between APT SI and Ki-67 LI in gliomas 29 , meningiomas 30 , and rectal carcinomas 31 , no correlation was found in rectal adenocarcinomas 51 . There have been few studies on the utility of APT imaging in the differential diagnosis of different breast tumors 26,28 , and further investigation will be required to determine whether there is an association between APT SI and Ki-67 LI.…”

“…We found that the combined ADC change using different T d values had a signi cant positive correlation with APT SI. Previous studies have reported that time-dependent DWI or CEST imaging might provide information about tumor microstructure indicating tumor proliferation in oncologic imaging [28][29][30][31][32] . Comparisons of APT SI and IVIM parameters in cervical cancers 33 , gliomas 34 , and hepatocellular carcinomas 35 , as well as comparisons of APT SI and diffusion kurtosis imaging in rectal carcinomas 36 , have been reported.…”

“…Amide protons from mobile proteins and peptides are typical endogenous CEST agents. Several investigations have reported that amide proton transfer (APT) imaging might be useful to predict tumor proliferation indices such as the Ki-67 index [28][29][30][31] .…”

Amide proton transfer imaging in differentiation of type II and type I endometrial carcinoma: a pilot study

“…Mobile proteins and peptides are thought to have a close relationship with tumor growth activity. The clinical utility of APT imaging has already been demonstrated in glioma, lung cancer, prostate cancer, and rectal cancers [15][16][17][18]. In gynecology, APT signals have demonstrated a correlation with the histologic grades of endometrioid endometrial carcinoma [19] and the efficacy in differentiating cervical cancer from normal cervical tissue [20].…”

Editorial for “Comparative Analysis of Amide Proton Transfer MRI and Diffusion‐Weighted Imaging in Assessing p53 and Ki‐67 Expression of Rectal Adenocarcinoma”

“…In this issue of JMRI, the article by Li et al 10 fits into this scenario, and advances our understanding of rectal cancer by exploiting the application of APT MRI for the detection of diagnostic and prognostic noninvasive MRI markers. In this well‐designed study the authors found significantly higher APT signal intensity in high‐grade tumors, more advanced‐stage tumors, and in tumors with lymph node metastases.…”