Abstract
PurposeTo investigate the significance of collagen in predicting the aggressiveness of rectal tumors in patients, examined in vivo based on tomoelastography quantified stiffness and ex vivo by histologically measured collagen volume fraction (CVF).Experimental Design170 patients with suspected rectal cancer were prospectively enrolled and underwent preoperative magnetic resonance imaging (MRI) and rectal tomoelastography, a technique based on multifrequency magnetic resonance elastography. Histopathologic analysis identified eighty patients with rectal cancer who were divided into subgroups by tumor-node (TN) stage, prognostic stage, and risk level. Rectal tumor stiffness was correlated with histopathologic CVF. Area-under-the-curve (AUC) and contingency analysis were used to evaluate the performance of rectal stiffness in distinguishing tumor stages which was compared to standard clinical MRIResultsIn vivo tomoelastography revealed that rectal tumor stiffened significantly with increased TN stage (p<0.05). Tumors with poorly differentiated status, perineural and lymphovascular invasion also displayed higher stiffness than well-to-moderately differentiated, noninvasive tumors (all p<0.05). Similar to in vivo stiffness, CVF indicated an abnormally high collagen content in tumors with perineural invasion and poor differentiation status. CVF was also positively correlated with stiffness (p<0.05). Most importantly, both stiffness (AUROC: 0.82) and CVF (AUROC: 0.89) demonstrated very good diagnostic accuracy in detecting rectal tumors that have high risk for progressing to an aggressive state with poorer prognosis.ConclusionIn human rectal carcinomas, overexpression of collagen is correlated with increased tissue stiffness and high risk for tumor advancing more aggressively. In vivo tomoelastography quantifies rectal tumor stiffness which improves the diagnostic performance of standard MRI in the assessment of lymph nodes metastasis. Therefore, in vivo stiffness mapping by tomoelastography can predict rectal tumor aggressiveness and add diagnostic value to MRI.
Highlights
Colorectal cancer (CRC) is the third most common cancer in men and the second most common cancer in women [1]
Based on histopathological analysis of surgically resected specimens, 32 patients whose tumors did not extend beyond the rectal muscularis propria were grouped and assigned to pT1– 2 stages (16 pT1 cases and 16 pT2 cases), while the remaining 48 patients with confirmed tumor infiltration beyond the muscularis propria were pooled into pT3–4 stages (41 pT3 cases and 7 pT4 cases)
Our study addresses this need by rectal tomoelastography which, for the first time, allowed us to quantify in vivo stiffness in patients with rectal cancer as a new imaging marker for extracellular matrix (ECM) protein deposition
Summary
Colorectal cancer (CRC) is the third most common cancer in men and the second most common cancer in women [1]. The Union for International Cancer Control and American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system is widely used for the clinical assessment of patients with colorectal cancer [2]. As recommended by the National Comprehensive Cancer Network (NCCN), histopathologic features such as number of positive nodes, lymphovascular invasion (LVI), perineural invasion (PNI), and poor differentiation have been recognized as high-risk factors for local recurrence and distant metastasis [4]. Morphological features provided by routine MRI are limited in assessing lymph nodes status [31,32,33], histopathologic risk factors such as PNI, LVI, as well as the degree of tumor differentiation. MRE could be of complementary value to current MRI by providing stiffness as a quantitative imaging marker for ECM remodeling during tumor progression for improved preoperative staging, risk stratification, and prediction of therapeutic efficiency in rectal cancer
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