TY - JOUR

T1 - Intratumor heterogeneity is biomarker specific and challenges the association with heterogeneity in multimodal functional imaging in head and neck squamous cell carcinoma

AU - Rasmussen, Jacob H

AU - Olin, Anders B

AU - Lelkaitis, Giedrius

AU - Hansen, Adam E

AU - Andersen, Flemming L

AU - Johannesen, Helle H

AU - Kjaer, Andreas

AU - Fischer, Barbara M

AU - Specht, Lena

AU - Bentzen, Søren M

AU - von Buchwald, Christian

AU - Wessel, Irene

AU - Vogelius, Ivan R

N1 - Copyright © 2021 Elsevier B.V. All rights reserved.

PY - 2021/6

Y1 - 2021/6

N2 - RATIONALE: Tumor biopsy cannot detect heterogeneity and an association between heterogeneity in functional imaging and molecular biology will have an impact on both diagnostics and treatment possibilities.PURPOSE: Multiparametric imaging can provide 3D information on functional aspects of a tumor and may be suitable for predicting intratumor heterogeneity. Here, we investigate the correlation between intratumor heterogeneity assessed with multiparametric imaging and multiple-biopsy immunohistochemistry.METHODS: In this prospective study, patients with primary or recurrent head and neck squamous cell carcinoma (HNSCC) underwent PET/MRI scanning prior to surgery. Tumors were removed en bloc and six core biopsies were used for immunohistochemical (IHC) staining with a predefined list of biomarkers: p40, p53, EGFR, Ki-67, GLUT1, VEGF, Bcl-2, CAIX, PD-L1. Intratumor heterogeneity of each IHC biomarker was quantified by calculating the coefficient of variation (CV) in tumor proportion score among the six core biopsies within each tumor lesion. The heterogeneity in the imaging biomarkers was assessed by calculating CV in 18F-fluorodeoxyglucose (FDG)-uptake, diffusion and perfusion. Concordance of the two variance measures was quantified using Spearman's rank correlation RESULTS: Twenty-eight patients with a total of 33 lesions were included. There was considerable heterogeneity in most of the IHC biomarkers especially in GLUT1, PD-L1, Ki-67, CAIX and p53, however we only observed a correlation between the heterogeneity in GLUT1 and p53 and between Ki-67 and EGFR. Heterogeneity in FDG uptake and diffusion correlated with heterogeneity in cell density.CONCLUSION: Considerable heterogeneity of IHC biomarkers was found, however, only few and weak correlations between the studied IHC markers were observed. The studied functional imaging biomarkers showed weak associations with heterogeneity in some of the IHC biomarkers. Thus, biological heterogeneity is not a general tumor characteristic but depends on the specific biomarker or imaging modality.

AB - RATIONALE: Tumor biopsy cannot detect heterogeneity and an association between heterogeneity in functional imaging and molecular biology will have an impact on both diagnostics and treatment possibilities.PURPOSE: Multiparametric imaging can provide 3D information on functional aspects of a tumor and may be suitable for predicting intratumor heterogeneity. Here, we investigate the correlation between intratumor heterogeneity assessed with multiparametric imaging and multiple-biopsy immunohistochemistry.METHODS: In this prospective study, patients with primary or recurrent head and neck squamous cell carcinoma (HNSCC) underwent PET/MRI scanning prior to surgery. Tumors were removed en bloc and six core biopsies were used for immunohistochemical (IHC) staining with a predefined list of biomarkers: p40, p53, EGFR, Ki-67, GLUT1, VEGF, Bcl-2, CAIX, PD-L1. Intratumor heterogeneity of each IHC biomarker was quantified by calculating the coefficient of variation (CV) in tumor proportion score among the six core biopsies within each tumor lesion. The heterogeneity in the imaging biomarkers was assessed by calculating CV in 18F-fluorodeoxyglucose (FDG)-uptake, diffusion and perfusion. Concordance of the two variance measures was quantified using Spearman's rank correlation RESULTS: Twenty-eight patients with a total of 33 lesions were included. There was considerable heterogeneity in most of the IHC biomarkers especially in GLUT1, PD-L1, Ki-67, CAIX and p53, however we only observed a correlation between the heterogeneity in GLUT1 and p53 and between Ki-67 and EGFR. Heterogeneity in FDG uptake and diffusion correlated with heterogeneity in cell density.CONCLUSION: Considerable heterogeneity of IHC biomarkers was found, however, only few and weak correlations between the studied IHC markers were observed. The studied functional imaging biomarkers showed weak associations with heterogeneity in some of the IHC biomarkers. Thus, biological heterogeneity is not a general tumor characteristic but depends on the specific biomarker or imaging modality.

KW - Biomarkers

KW - Biomarkers, Tumor

KW - Fluorodeoxyglucose F18

KW - Head and Neck Neoplasms/diagnostic imaging

KW - Humans

KW - Neoplasm Recurrence, Local

KW - Positron-Emission Tomography

KW - Prospective Studies

KW - Squamous Cell Carcinoma of Head and Neck

U2 - 10.1016/j.ejrad.2021.109668

DO - 10.1016/j.ejrad.2021.109668

M3 - Journal article

C2 - 33848777

VL - 139

JO - European Journal of Radiology

JF - European Journal of Radiology

SN - 0720-048X

M1 - 109668

ER -