Evaluation of Lymphatic Vessel Invasion Determined by D2-40 Using Preoperative MRI-Based Radiomics for Invasive Breast Cancer

Published:December 29, 2022DOI:

      Rationale and Objectives

      Preoperative prediction of LVI status can facilitate personalized therapeutic planning. This study aims to investigate the efficacy of preoperative MRI-based radiomics for predicting lymphatic vessel invasion (LVI) determined by D2-40 in patients with invasive breast cancer.

      Materials and Methods

      A total of 203 patients with pathologically confirmed invasive breast cancer, who underwent preoperative breast MRI, were retrospectively enrolled and randomly assigned to the following cohorts: training cohort (n=141) and test cohort (n=62). Then, univariate and multivariate logistic regression were performed to select independent risk factors and build a clinical model. Afterwards, least absolute shrinkage and selection operator (LASSO) logistic regression was performed to select predictive features extracted from the early and delay enhancement dynamic contrast-enhanced (DCE)-MRI images, and a radiomics signature was established. Subsequently, a nomogram model was constructed by incorporating the radiomics score and risk factors. Receiver operating characteristic curves were performed to determine the performance of various models. The efficacy of the various models was evaluated using calibration and decision curves.


      Fourteen radiomics features were selected to construct the radiomics model. The size of the lymph node was identified as an independent risk factor of the clinical model. The nomogram model demonstrated the best calibration and discrimination performance in both the training and test cohorts, with an area under the curve of 0.873 (95% confidence interval [CI]: 0.807-0.923) and 0.902 (95% CI: 0.800-0.963), respectively. The decision curve illustrated that the nomogram model added more net benefits, when compared to the radiomics signature and clinical model.


      The nomogram model based on preoperative DCE-MRI images exhibits satisfactory efficacy for the noninvasive prediction of LVI determined by D2-40 in invasive breast cancer.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Academic Radiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • David Nathanson S
        • Leonard-Murali S
        • Burmeister C
        • et al.
        Clinicopathological evaluation of the potential anatomic pathways of systemic metastasis from primary breast cancer suggests an orderly spread through the regional lymph nodes.
        Ann Surg Oncol. 2020; 27: 4810-4818
        • Gujam FJ
        • Going JJ
        • Mohammed ZM
        • et al.
        Immunohistochemical detection improves the prognostic value of lymphatic and blood vessel invasion in primary ductal breast cancer.
        BMC Cancer. 2014; 14: 676
        • Braun M
        • Flucke U
        • Debald M
        • et al.
        Detection of lymphovascular invasion in early breast cancer by D2-40 (podoplanin): a clinically useful predictor for axillary lymph node metastases.
        Breast Cancer Res Treat. 2008; 112: 503-511
        • Zhong YM
        • Tong F
        • Shen J.
        Lympho-vascular invasion impacts the prognosis in breast-conserving surgery: a systematic review and meta-analysis.
        BMC Cancer. 2022; 22: 102
        • Gujam FJ
        • Going JJ
        • Edwards J
        • et al.
        The role of lymphatic and blood vessel invasion in predicting survival and methods of detection in patients with primary operable breast cancer.
        Crit Rev Oncol Hematol. 2014; 89: 231-241
        • Vosough Z
        • Golbini S
        • Sharbatdaran M
        • et al.
        D2-40 A helpful marker in assessment of lymphatic vessel invasion in carcinoma of breast.
        Iran J Pathol. 2021; 16: 96-102
        • Hoda SA
        • Hoda RS
        • Merlin S
        • et al.
        Issues relating to lymphovascular invasion in breast carcinoma.
        Adv Anat Pathol. 2006; 13: 308-315
        • Mohammed RA
        • Martin SG
        • Mahmmod AM
        • et al.
        Objective assessment of lymphatic and blood vascular invasion in lymph node-negative breast carcinoma: findings from a large case series with long-term follow-up.
        J Pathol. 2011; 223: 358-365
        • Van den Eynden GG
        • Van der Auwera I
        • Van Laere SJ
        • et al.
        Distinguishing blood and lymph vessel invasion in breast cancer: a prospective immunohistochemical study.
        Br J Cancer. 2006; 94: 1643-1649
        • Schacht V
        • Dadras SS
        • Johnson LA
        • et al.
        Up-regulation of the lymphatic marker podoplanin, a mucin-type transmembrane glycoprotein, in human squamous cell carcinomas and germ cell tumors.
        Am J Pathol. 2005; 166: 913-921
        • Evangelou E
        • Kyzas PA
        • Trikalinos TA.
        Comparison of the diagnostic accuracy of lymphatic endothelium markers: Bayesian approach.
        Mod Pathol. 2005; 18: 1490-1497
        • de Mascarel I
        • MacGrogan G
        • Debled M
        • et al.
        D2-40 in breast cancer: should we detect more vascular emboli?.
        Mod Pathol. 2009; 22: 216-222
        • Uematsu T
        • Kasami M
        • Watanabe J
        • et al.
        Is lymphovascular invasion degree one of the important factors to predict neoadjuvant chemotherapy efficacy in breast cancer?.
        Breast Cancer. 2011; 18: 309-313
        • Cheung SM
        • Husain E
        • Mallikourti V
        • et al.
        Intra-tumoural lipid composition and lymphovascular invasion in breast cancer via non-invasive magnetic resonance spectroscopy.
        Eur Radiol. 2021; 31: 3703-3711
        • Peters NH
        • Borel Rinkes IH
        • Zuithoff NP
        • et al.
        Meta-analysis of MR imaging in the diagnosis of breast lesions.
        Radiology. 2008; 246: 116-124
        • Mann RM
        • Cho N
        • Moy L.
        Breast MRI: State of the Art.
        Radiology. 2019; 292: 520-536
        • Choi BB.
        Dynamic contrast enhanced-MRI and diffusion-weighted image as predictors of lymphovascular invasion in node-negative invasive breast cancer.
        World J Surg Oncol. 2021; 19: 76
        • Igarashi T
        • Furube H
        • Ashida H
        • et al.
        Breast MRI for prediction of lymphovascular invasion in breast cancer patients with clinically negative axillary lymph nodes.
        Eur J Radiol. 2018; 107: 111-118
        • Cheon H
        • Kim HJ
        • Lee SM
        • et al.
        Preoperative MRI features associated with lymphovascular invasion in node-negative invasive breast cancer: a propensity-matched analysis.
        J Magn Reson Imaging. 2017; 46: 1037-1044
        • Ni-Jia-Ti MY
        • Ai-Hai-Ti DL
        • Huo-Jia AS
        • et al.
        Development of a risk-stratification scoring system for predicting lymphovascular invasion in breast cancer.
        BMC Cancer. 2020; 20: 94
        • Kayadibi Y
        • Kocak B
        • Ucar N
        • et al.
        MRI Radiomics of breast cancer: machine learning-based prediction of lymphovascular invasion status.
        Acad Radiol. 2022; 29: S126-S134
        • Zhang J
        • Wang G
        • Ren J
        • et al.
        Multiparametric MRI-based radiomics nomogram for preoperative prediction of lymphovascular invasion and clinical outcomes in patients with breast invasive ductal carcinoma.
        Eur Radiol. 2022; 32: 4079-4089
        • Liu Z
        • Feng B
        • Li C
        • et al.
        Preoperative prediction of lymphovascular invasion in invasive breast cancer with dynamic contrast-enhanced-MRI-based radiomics.
        J Magn Reson Imaging. 2019; 50: 847-857
        • Li C
        • Song L
        • Yin J.
        Intratumoral and peritumoral radiomics based on functional parametric maps from breast DCE-MRI for prediction of HER-2 and Ki-67 status.
        J Magn Reson Imaging. 2021; 54: 703-714
        • Hyun SJ
        • Kim EK
        • Moon HJ
        • et al.
        Preoperative axillary lymph node evaluation in breast cancer patients by breast magnetic resonance imaging (MRI): can breast MRI exclude advanced nodal disease?.
        Eur Radiol. 2016; 26: 386-3873
        • Giuliano AE
        • Connolly JL
        • Edge SB
        • et al.
        Breast cancer-major changes in the American joint committee on cancer eighth edition cancer staging manual [.
        CA Cancer J Clin. 2017; 67: 290-303
        • Lee AH
        • Pinder SE
        • Macmillan RD
        • et al.
        Prognostic value of lymphovascular invasion in women with lymph node negative invasive breast carcinoma.
        Eur J Cancer. 2006; 42: 357-362
        • de Mascarel I
        • Bonichon F
        • Durand M
        • et al.
        Obvious peritumoral emboli: an elusive prognostic factor reappraised. Multivariate analysis of 1320 node-negative breast cancers.
        Eur J Cancer. 1998; 34: 5-65
        • Mori N
        • Mugikura S
        • Takasawa C
        • et al.
        Peritumoral apparent diffusion coefficients for prediction of lymphovascular invasion in clinically node-negative invasive breast cancer [published correction appears in Eur Radiol. 2016 Feb;26(2):340-1].
        Eur Radiol. 2016; 26: 331-339
        • Park NJ
        • Jeong JY
        • Park JY
        • et al.
        Peritumoral edema in breast cancer at preoperative MRI: an interpretative study with histopathological review toward understanding tumor microenvironment.
        Sci Rep. 2021; 11: 12992
        • Liu S
        • Sun W
        • Yang S
        • et al.
        Deep learning radiomic nomogram to predict recurrence in soft tissue sarcoma: a multi-institutional study.
        Eur Radiol. 2022; 32: 793-805
        • Chetan MR
        • Gleeson FV.
        Radiomics in predicting treatment response in non-small-cell lung cancer: current status, challenges and future perspectives.
        Eur Radiol. 2021; 31: 1049-1058
        • Fiz F
        • Viganò L
        • Gennaro N
        • et al.
        Radiomics of liver metastases: a systematic review.
        Cancers (Basel). 2020; 12: 2881
        • Yang L
        • Gu D
        • Wei J
        • et al.
        A Radiomics nomogram for preoperative prediction of microvascular invasion in hepatocellular carcinoma.
        Liver Cancer. 2019; 8: 373-386