Sistema de Salut de Catalunya
Institut Català de la Salut
[Mondaza-Hernandez JL] Health Research Institute Fundacion Jimenez Diaz, Universidad Autonoma de Madrid, Madrid, Spain University Hospital General de Villalba, Madrid, Spain. [Hindi N] Health Research Institute Fundacion Jimenez Diaz, Universidad Autonoma de Madrid, Madrid, Spain. University Hospital General de Villalba, Madrid, Spain. Medical Oncology Department, Fundación Jimenez Diaz University Hospital, Madrid, Spain. [Fernandez-Serra A] Molecular Biology Department, Fundación Instituto Valenciano de Oncologia, Valencia, Spain. [Ramos R] Pathology Department, University Hospital Son Espases, Mallorca, Spain. [Gonzalez-Cámpora R] Pathology Department, Hospital Quironsalud, Cordoba, Cordoba, Spain. [Gómez-Mateo MC] Department of Pathology, Hospital Universitario Miguel Servet, Zaragoza, Spain. [Valverde C] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
2025-01-07T07:38:30Z
2025-01-07T07:38:30Z
2024-11-04
Alveolar soft-part sarcoma; Immunotherapy; Prognostic biomarker
Sarcoma alveolar de partes blandas; Inmunoterapia; Biomarcador pronóstico
Sarcoma alveolar de parts toves; Immunoteràpia; Biomarcador pronòstic
Background: Alveolar soft-part sarcoma (ASPS) is a rare tumor driven by the ASPSCR1-TFE3 fusion protein, with a propensity for metastasis. Prognostic factors remain poorly understood, and traditional chemotherapies are largely ineffective. Recent interest lies in immune checkpoint inhibitors (ICIs), yet predictive biomarkers for treatment response are lacking. Previous studies have shown promising results with ICIs in ASPS, indicating a need for further investigation into biomarkers associated with immune response. Objectives: To identify prognostic biomarkers in ASPS and to explore the role of immune-related markers, particularly L1CAM, in predicting patient outcomes. Design: A retrospective cohort study of 19 ASPS patients registered in the GEIS database. The study involved the collection of clinical and histopathological data, followed by an analysis of immune markers and gene expression profiles to identify potential prognostic indicators. Methods: Clinical and histopathological data were retrospectively collected from the GEIS-26 study cohort of 19 ASPS patients. Immunohistochemistry was performed to evaluate immune markers programmed death-1 ligand (PD-L1), programmed death-1, FAS, FASL, CD8, CD3, and CD4. An HTG ImmunOncology panel was conducted on formalin-fixed paraffin-embedded samples to explore gene expression. Effects of differentially expressed genes on survival were explored by Kaplan–Meier. Results: PD-L1 positivity was widely observed (63%) in tumors, and CD8+ lymphocytic infiltration was common. High CD8 density correlated with greater overall survival (OS) while not statistically significant. No associations were found for other immune markers. L1CAM was identified as differentially expressed in patients with low CD8 infiltration and correlated negatively with OS. Conclusion: High L1CAM expression correlated with poorer OS, highlighting its potential as a prognostic marker and therapeutic target in ASPS. Immunomodulatory interventions may hold promise, as evidenced by PD-L1 expression and CD8+ infiltration. Further research, including larger cohorts and international collaborations, is needed to validate these findings and explore therapeutic strategies targeting L1CAM in ASPS.
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: GEIS-26/GEIS.
Article
Published version
English
Càncer - Immunoteràpia; Tumors de parts toves - Immunoteràpia; Marcadors bioquímics; Càncer - Prognosi; DISEASES::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Connective and Soft Tissue::Neoplasms, Muscle Tissue::Sarcoma, Alveolar Soft Part; CHEMICALS AND DRUGS::Biological Factors::Biomarkers; CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents::Antineoplastic Agents, Immunological; DISEASES::Neoplasms::Neoplasms by Site::Soft Tissue Neoplasms; ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis; ENFERMEDADES::neoplasias::neoplasias por tipo histológico::neoplasias de tejido conjuntivo y de tejidos blandos::neoplasias de tejido muscular::sarcoma alveolar de partes blandas; COMPUESTOS QUÍMICOS Y DROGAS::factores biológicos::biomarcadores; COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos::inmunoterapia antineoplásica; ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de los tejidos blandos; TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico
SAGE Publications
Therapeutic Advances in Medical Oncology;16
https://doi.org/10.1177/17588359241293951
Attribution-NonCommercial 4.0 International
http://creativecommons.org/licenses/by-nc/4.0/
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