Characterizing the Invasive Tumor Front of Aggressive Uterine Adenocarcinoma and Leiomyosarcoma
Sanegre, Sabina (Department of Pathology, School of Medical, University of Valencia-INCLIVA)
Eritja, Núria (Institut d'Investigació Biomèdica de Bellvitge)
de Andrea, Carlos (Clínica Universidad de Navarra)
Diaz-Martin, Juan (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Diaz-Lagares, Angel (Hospital Clínico Universitario (Santiago de Compostela, Galícia))
Jácome, María Amalia (Universidade da Coruña)
Salguero-Aranda, Carmen (Hopital Universitario Virgen del Rocío)
García-Ros, David (Clínica Universidad de Navarra)
Davidson, Ben (Norwegian Radium Hospital)
Lopez, Rafel (Instituto de Investigación Sanitaria de Santiago (IDIS))
Melero, Ignacio (Clínica Universidad de Navarra)
Navarro, Samuel (Universitat de València)
Ramon y Cajal, Santiago (Hospital Universitari Vall d'Hebron. Institut de Recerca)
De Álava, Enrique (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Matias-Guiu, Xavier (Institut d'Investigació Biomèdica de Bellvitge)
Noguera, Rosa (Universitat de València)
Universitat Autònoma de Barcelona

Date:	2021
Abstract:	The invasive tumor front (the tumor-host interface) is vitally important in malignant cell progression and metastasis. Tumor cell interactions with resident and infiltrating host cells and with the surrounding extracellular matrix and secreted factors ultimately determine the fate of the tumor. Herein we focus on the invasive tumor front, making an in-depth characterization of reticular fiber scaffolding, infiltrating immune cells, gene expression, and epigenetic profiles of classified aggressive primary uterine adenocarcinomas (24 patients) and leiomyosarcomas (11 patients). Sections of formalin-fixed samples before and after microdissection were scanned and studied. Reticular fiber architecture and immune cell infiltration were analyzed by automatized algorithms in colocalized regions of interest. Despite morphometric resemblance between reticular fibers and high presence of macrophages, we found some variance in other immune cell populations and distinctive gene expression and cell adhesion-related methylation signatures. Although no evident overall differences in immune response were detected at the gene expression and methylation level, impaired antimicrobial humoral response might be involved in uterine leiomyosarcoma spread. Similarities found at the invasive tumor front of uterine adenocarcinomas and leiomyosarcomas could facilitate the use of common biomarkers and therapies. Furthermore, molecular and architectural characterization of the invasive front of uterine malignancies may provide additional prognostic information beyond established prognostic factors.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Tumor-host interface ; Tumor microenvironment ; Extracellular matrix ; Reticular fibers ; Immune cells ; Gene expression ; Epigenetic profiles
Published in:	Frontiers in Cell and Developmental Biology, Vol. 9 (june 2021) , ISSN 2296-634X

DOI: 10.3389/fcell.2021.670185
PMID: 34150764

19 p, 6.7 MB

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