Standardized Pathology Screening of Mature Tertiary Lymphoid Structures in Cancers

Lucile Vanhersecke; Antoine Bougouin; Amandine Crombé; Maxime Brunet; Casimir Sofeu; Marie Parrens; Hugo Pierron; Benjamin Bonhomme; Nicolas Lembege; Christophe Rey; Valérie Velasco; Isabelle Soubeyran; Hugues Begueret; Alban Bessede; Carine Bellera; Jean Yves Scoazec; Antoine Italiano; Catherine Sautès Fridman; Wolf H. Fridman; François Le Loarer

doi:10.1016/j.labinv.2023.100063

Standardized Pathology Screening of Mature Tertiary Lymphoid Structures in Cancers

Lucile Vanhersecke, Antoine Bougouin, Amandine Crombé, Maxime Brunet, Casimir Sofeu, Marie Parrens, Hugo Pierron, Benjamin Bonhomme, Nicolas Lembege, Christophe Rey, Valérie Velasco, Isabelle Soubeyran, Hugues Begueret, Alban Bessede, Carine Bellera, Jean Yves Scoazec, Antoine Italiano, Catherine Sautès Fridman, Wolf H. Fridman, François Le Loarer

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Résumé

Mature tertiary lymphoid structures (mTLSs) are organized lymphoid structures containing B lymphocytes admixed to CD23+ follicular dendritic cells. Their presence has been linked to improved survival and sensitivity to immune checkpoint inhibitors in several cancers, emerging as a promising pancancer biomarker. However, the requirements for any biomarker are clear methodology, proven feasibility, and reliability. In 357 patients’ samples, we studied tertiary lymphoid structures (TLSs) parameters using multiplex immunofluorescence (mIF), hematoxylin-eosin-saffron (HES) staining, double CD20/CD23 staining, and single CD23 immunohistochemistry. The cohort included carcinomas (n = 211) and sarcomas (n = 146), gathering biopsies (n = 170), and surgical specimens (n = 187). mTLSs were defined as TLSs containing either a visible germinal center on HES staining or CD23+ follicular dendritic cells. Focusing on 40 TLSs assessed using mIF, double CD20/CD23 staining was less sensitive than mIF to assess maturity in 27.5% (n = 11/40) but was rescued by single CD23 staining in 90.9% (n = 10/11). In 97 patients, several samples (n = 240) were reviewed to characterize TLS distribution. The likelihood of finding TLSs in surgical material was 6.1 higher than in biopsy and 2.0 higher in primary samples than in metastasis after adjustment with a type of sample. Interrater agreement rates over 4 examiners were 0.65 (Fleiss kappa, 95% CI [0.46, 0.90]) for the presence of TLS and 0.90 for maturity (95% CI [0.83, 0.99]). In this study, we propose a standardized method to screen mTLSs in cancer samples using HES staining and immunohistochemistry that can be applied to all specimens.

langue originale	Anglais
Numéro d'article	100063
journal	Laboratory Investigation
Volume	103
Numéro de publication	5
Les DOIs	https://doi.org/10.1016/j.labinv.2023.100063
état	Publié - 1 mai 2023

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10.1016/j.labinv.2023.100063

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Vanhersecke, L., Bougouin, A., Crombé, A., Brunet, M., Sofeu, C., Parrens, M., Pierron, H., Bonhomme, B., Lembege, N., Rey, C., Velasco, V., Soubeyran, I., Begueret, H., Bessede, A., Bellera, C., Scoazec, J. Y., Italiano, A., Fridman, C. S., Fridman, W. H., & Le Loarer, F. (2023). Standardized Pathology Screening of Mature Tertiary Lymphoid Structures in Cancers. Laboratory Investigation, 103(5), Article 100063. https://doi.org/10.1016/j.labinv.2023.100063

@article{11c85e2955f3412bb3c261e5f4a6ed89,

title = "Standardized Pathology Screening of Mature Tertiary Lymphoid Structures in Cancers",

abstract = "Mature tertiary lymphoid structures (mTLSs) are organized lymphoid structures containing B lymphocytes admixed to CD23+ follicular dendritic cells. Their presence has been linked to improved survival and sensitivity to immune checkpoint inhibitors in several cancers, emerging as a promising pancancer biomarker. However, the requirements for any biomarker are clear methodology, proven feasibility, and reliability. In 357 patients{\textquoteright} samples, we studied tertiary lymphoid structures (TLSs) parameters using multiplex immunofluorescence (mIF), hematoxylin-eosin-saffron (HES) staining, double CD20/CD23 staining, and single CD23 immunohistochemistry. The cohort included carcinomas (n = 211) and sarcomas (n = 146), gathering biopsies (n = 170), and surgical specimens (n = 187). mTLSs were defined as TLSs containing either a visible germinal center on HES staining or CD23+ follicular dendritic cells. Focusing on 40 TLSs assessed using mIF, double CD20/CD23 staining was less sensitive than mIF to assess maturity in 27.5% (n = 11/40) but was rescued by single CD23 staining in 90.9% (n = 10/11). In 97 patients, several samples (n = 240) were reviewed to characterize TLS distribution. The likelihood of finding TLSs in surgical material was 6.1 higher than in biopsy and 2.0 higher in primary samples than in metastasis after adjustment with a type of sample. Interrater agreement rates over 4 examiners were 0.65 (Fleiss kappa, 95% CI [0.46, 0.90]) for the presence of TLS and 0.90 for maturity (95% CI [0.83, 0.99]). In this study, we propose a standardized method to screen mTLSs in cancer samples using HES staining and immunohistochemistry that can be applied to all specimens.",

keywords = "immune checkpoint inhibitors, immunotherapy, tertiary lymphoid structures (TLSs), tumor microenvironment",

author = "Lucile Vanhersecke and Antoine Bougouin and Amandine Cromb{\'e} and Maxime Brunet and Casimir Sofeu and Marie Parrens and Hugo Pierron and Benjamin Bonhomme and Nicolas Lembege and Christophe Rey and Val{\'e}rie Velasco and Isabelle Soubeyran and Hugues Begueret and Alban Bessede and Carine Bellera and Scoazec, {Jean Yves} and Antoine Italiano and Fridman, {Catherine Saut{\`e}s} and Fridman, {Wolf H.} and {Le Loarer}, Fran{\c c}ois",

note = "Publisher Copyright: {\textcopyright} 2023 United States & Canadian Academy of Pathology",

year = "2023",

month = may,

day = "1",

doi = "10.1016/j.labinv.2023.100063",

language = "English",

volume = "103",

journal = "Laboratory Investigation",

issn = "0023-6837",

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Vanhersecke, L, Bougouin, A, Crombé, A, Brunet, M, Sofeu, C, Parrens, M, Pierron, H, Bonhomme, B, Lembege, N, Rey, C, Velasco, V, Soubeyran, I, Begueret, H, Bessede, A, Bellera, C, Scoazec, JY, Italiano, A, Fridman, CS, Fridman, WH & Le Loarer, F 2023, 'Standardized Pathology Screening of Mature Tertiary Lymphoid Structures in Cancers', Laboratory Investigation, VOL. 103, Numéro 5, 100063. https://doi.org/10.1016/j.labinv.2023.100063

TY - JOUR

T1 - Standardized Pathology Screening of Mature Tertiary Lymphoid Structures in Cancers

AU - Vanhersecke, Lucile

AU - Bougouin, Antoine

AU - Crombé, Amandine

AU - Brunet, Maxime

AU - Sofeu, Casimir

AU - Parrens, Marie

AU - Pierron, Hugo

AU - Bonhomme, Benjamin

AU - Lembege, Nicolas

AU - Rey, Christophe

AU - Velasco, Valérie

AU - Soubeyran, Isabelle

AU - Begueret, Hugues

AU - Bessede, Alban

AU - Bellera, Carine

AU - Scoazec, Jean Yves

AU - Italiano, Antoine

AU - Fridman, Catherine Sautès

AU - Fridman, Wolf H.

AU - Le Loarer, François

PY - 2023/5/1

Y1 - 2023/5/1

N2 - Mature tertiary lymphoid structures (mTLSs) are organized lymphoid structures containing B lymphocytes admixed to CD23+ follicular dendritic cells. Their presence has been linked to improved survival and sensitivity to immune checkpoint inhibitors in several cancers, emerging as a promising pancancer biomarker. However, the requirements for any biomarker are clear methodology, proven feasibility, and reliability. In 357 patients’ samples, we studied tertiary lymphoid structures (TLSs) parameters using multiplex immunofluorescence (mIF), hematoxylin-eosin-saffron (HES) staining, double CD20/CD23 staining, and single CD23 immunohistochemistry. The cohort included carcinomas (n = 211) and sarcomas (n = 146), gathering biopsies (n = 170), and surgical specimens (n = 187). mTLSs were defined as TLSs containing either a visible germinal center on HES staining or CD23+ follicular dendritic cells. Focusing on 40 TLSs assessed using mIF, double CD20/CD23 staining was less sensitive than mIF to assess maturity in 27.5% (n = 11/40) but was rescued by single CD23 staining in 90.9% (n = 10/11). In 97 patients, several samples (n = 240) were reviewed to characterize TLS distribution. The likelihood of finding TLSs in surgical material was 6.1 higher than in biopsy and 2.0 higher in primary samples than in metastasis after adjustment with a type of sample. Interrater agreement rates over 4 examiners were 0.65 (Fleiss kappa, 95% CI [0.46, 0.90]) for the presence of TLS and 0.90 for maturity (95% CI [0.83, 0.99]). In this study, we propose a standardized method to screen mTLSs in cancer samples using HES staining and immunohistochemistry that can be applied to all specimens.

AB - Mature tertiary lymphoid structures (mTLSs) are organized lymphoid structures containing B lymphocytes admixed to CD23+ follicular dendritic cells. Their presence has been linked to improved survival and sensitivity to immune checkpoint inhibitors in several cancers, emerging as a promising pancancer biomarker. However, the requirements for any biomarker are clear methodology, proven feasibility, and reliability. In 357 patients’ samples, we studied tertiary lymphoid structures (TLSs) parameters using multiplex immunofluorescence (mIF), hematoxylin-eosin-saffron (HES) staining, double CD20/CD23 staining, and single CD23 immunohistochemistry. The cohort included carcinomas (n = 211) and sarcomas (n = 146), gathering biopsies (n = 170), and surgical specimens (n = 187). mTLSs were defined as TLSs containing either a visible germinal center on HES staining or CD23+ follicular dendritic cells. Focusing on 40 TLSs assessed using mIF, double CD20/CD23 staining was less sensitive than mIF to assess maturity in 27.5% (n = 11/40) but was rescued by single CD23 staining in 90.9% (n = 10/11). In 97 patients, several samples (n = 240) were reviewed to characterize TLS distribution. The likelihood of finding TLSs in surgical material was 6.1 higher than in biopsy and 2.0 higher in primary samples than in metastasis after adjustment with a type of sample. Interrater agreement rates over 4 examiners were 0.65 (Fleiss kappa, 95% CI [0.46, 0.90]) for the presence of TLS and 0.90 for maturity (95% CI [0.83, 0.99]). In this study, we propose a standardized method to screen mTLSs in cancer samples using HES staining and immunohistochemistry that can be applied to all specimens.

KW - immune checkpoint inhibitors

KW - immunotherapy

KW - tertiary lymphoid structures (TLSs)

KW - tumor microenvironment

UR - http://www.scopus.com/inward/record.url?scp=85157986242&partnerID=8YFLogxK

U2 - 10.1016/j.labinv.2023.100063

DO - 10.1016/j.labinv.2023.100063

M3 - Article

C2 - 36801637

AN - SCOPUS:85157986242

SN - 0023-6837

VL - 103

JO - Laboratory Investigation

JF - Laboratory Investigation

IS - 5

M1 - 100063

ER -