Fanconi Anemia: Matrix Remodeling and Oral Carcinogenesis

Fanconi anemia (FA) increases the risk of oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma; however, the stromal alterations associated with FA-related oral lesions remain poorly defined. We investigated whether extracellular matrix (ECM) remodeling represents a quantifiable feature of FA-associated OPMDs. A total of 119 participants were included: controls with normal mucosa or oral leukoplakia (OL) and individuals with FA. Histopathological and immunohistochemical analyses (p53, Ki-67, α-SMA, and elastin), picrosirius red staining, and multiphoton microscopy combining second-harmonic generation and 2-photon fluorescence were performed, complemented by salivary and transcriptomic profiling. Additionally, Fanca -deficient mice were used to assess stromal remodeling. Compared with sporadic OL, FA-OL exhibited reduced collagen density and elastin autofluorescence, a higher collagen-to-elastin ratio, and diminished p53 immunoreactivity. Salivary procollagen type I N-terminal propeptide showed exploratory associations with matrix-derived optical parameters. RNA sequencing of bulk biopsy tissue revealed an altered matrisome transcriptional signature, including enrichment of ECM structural gene sets and downregulation of selected ECM regulatory programs. In FA-related mouse models, collagen and elastin signals were similarly reduced. Collectively, these multimodal data identify ECM disruption as a reproducible feature associated with FA-OL. Matrix disorganization, together with altered epithelial p53 immunoreactivity, supports the hypothesis that epithelial and stromal alterations coexist across the FA-associated oral lesion spectrum.

Authors

Institutions

Publication Details

Journal
Journal of Dental Research
Published
2026-10-15
DOI
https://doi.org/10.1177/00220345261478636
Primary Topic
Oral Health Pathology and Treatment
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Fanconi Anemia: Matrix Remodeling and Oral Carcinogenesis

José Miguel Amenábar, Cassius Carvalho Torres‐Pereira, José Alcides Almeida de Arruda, Corina Lorz et al.
Journal of Dental Research
Oral Health Pathology and Treatment
article

Fanconi Anemia: Matrix Remodeling and Oral Carcinogenesis

José Miguel Amenábar, Cassius Carvalho Torres‐Pereira, José Alcides Almeida de Arruda, Corina Lorz, Victor Zanetti Drumond, Tarcı́lia Aparecida Silva, Ramón Garcı́a-Escudero, Leandro M. Malard, Nayara Conceição Marcos Santana, F. Ferré, Benjamin Fournier, Ariane Berdal, Nicolas Dupré, Paula Alves da Silva Rocha, S. Del Marro, R. Errazquin, W.C.S. Silva, S. Macari, A. Page, A. Pascual
article en

Abstract

Fanconi anemia (FA) increases the risk of oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma; however, the stromal alterations associated with FA-related oral lesions remain poorly defined. We investigated whether extracellular matrix (ECM) remodeling represents a quantifiable feature of FA-associated OPMDs. A total of 119 participants were included: controls with normal mucosa or oral leukoplakia (OL) and individuals with FA. Histopathological and immunohistochemical analyses (p53, Ki-67, α-SMA, and elastin), picrosirius red staining, and multiphoton microscopy combining second-harmonic generation and 2-photon fluorescence were performed, complemented by salivary and transcriptomic profiling. Additionally, Fanca -deficient mice were used to assess stromal remodeling. Compared with sporadic OL, FA-OL exhibited reduced collagen density and elastin autofluorescence, a higher collagen-to-elastin ratio, and diminished p53 immunoreactivity. Salivary procollagen type I N-terminal propeptide showed exploratory associations with matrix-derived optical parameters. RNA sequencing of bulk biopsy tissue revealed an altered matrisome transcriptional signature, including enrichment of ECM structural gene sets and downregulation of selected ECM regulatory programs. In FA-related mouse models, collagen and elastin signals were similarly reduced. Collectively, these multimodal data identify ECM disruption as a reproducible feature associated with FA-OL. Matrix disorganization, together with altered epithelial p53 immunoreactivity, supports the hypothesis that epithelial and stromal alterations coexist across the FA-associated oral lesion spectrum.

Journal of Dental Research
Universidade Federal de Minas Gerais (BR), Universidade Federal do Rio de Janeiro (BR), Inserm (FR), Université Paris Cité (FR), Instituto de Salud Carlos III (ES), Research Institute Hospital 12 de Octubre (ES), Hôpital Rothschild (FR), Assistance Publique – Hôpitaux de Paris (FR), Hospital Universitario 12 De Octubre (ES), Centro de Investigación Biomédica en Red de Cáncer (ES), Institut des Maladies Génétiques Imagine (FR), Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (ES), Santé Orale (FR), Universidade Federal do Paraná (BR)
Openalex Percentile: Top 10%
Oral Health Pathology and Treatment
DOISourceOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.