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Dynamic Contrast Enhanced MRI and Intravoxel Incoherent Motion to Identify Molecular Subtypes of Breast Cancer with Different Vascular Normalization Gene Expression

  • Wan-Chen Tsai (Department of Radiology, Koo Foundation Sun Yat-Sen Cancer Center) ;
  • Kai-Ming Chang (Department of Research, Koo Foundation Sun Yat-Sen Cancer Center) ;
  • Kuo-Jang Kao (Department of Research, Koo Foundation Sun Yat-Sen Cancer Center)
  • 투고 : 2020.06.11
  • 심사 : 2021.02.04
  • 발행 : 2021.07.01

초록

Objective: To assess the expression of vascular normalization genes in different molecular subtypes of breast cancer and to determine whether molecular subtypes with a higher vascular normalization gene expression can be identified using dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI). Materials and Methods: This prospective study evaluated 306 female (mean age ± standard deviation, 50 ± 10 years), recruited between January 2014 and August 2017, who had de novo breast cancer larger than 1 cm in diameter (308 tumors). DCE MRI followed by IVIM DWI studies using 11 different b-values (0 to 1200 s/mm2) were performed on a 1.5T MRI system. The Tofts model and segmented biexponential IVIM analysis were used. For each tumor, the molecular subtype (according to six [I-VI] subtypes and PAM50 subtypes), expression profile of genes for vascular normalization, pericytes, and normal vascular signatures were determined using freshly frozen tissue. Statistical associations between imaging parameters and molecular subtypes were examined using logistic regression or linear regression with a significance level of p = 0.05. Results: Breast cancer subtypes III and VI and PAM50 subtypes luminal A and normal-like exhibited a higher expression of genes for vascular normalization, pericyte markers, and normal vessel function signature (p < 0.001 for all) compared to other subtypes. Subtypes III and VI and PAM50 subtypes luminal A and normal-like, versus the remaining subtypes, showed significant associations with Ktrans, kep, vp, and IAUGCBN90 on DEC MRI, with relatively smaller values in the former. The subtype grouping was significantly associated with D, with relatively less restricted diffusion in subtypes III and VI and PAM50 subtypes luminal A and normal-like. Conclusion: DCE MRI and IVIM parameters may identify molecular subtypes of breast cancers with a different vascular normalization gene expression.

키워드

과제정보

Special thanks to Leighanne Jamie Chen for her English editing efforts, to Chen-Fang Hung and I-Ting Chen for assistance in data management; to Chien-Yuan Lin PhD. for MRI technique and set up assistance, and to the following members of Surgical Oncology for their care and treatment of patients: Chii-Ming Chen, Tsung-Yen Cheng, Benlong Yu, Tzu-Jung Tsai, Chih-Chun Lee, and Hung-Kuang Wei.

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