Dissecting and Reconstructing Matrix in Malignant Mesothelioma Through Histocell-Histochemistry Gradients for Clinical Applications.

Movat's pentachrome stain Picrosirius immunohistochemistry malignant mesothelioma prognosis

Journal

Frontiers in medicine
ISSN: 2296-858X
Titre abrégé: Front Med (Lausanne)
Pays: Switzerland
ID NLM: 101648047

Informations de publication

Date de publication:
2022
Historique:
received: 07 02 2022
accepted: 16 03 2022
entrez: 2 5 2022
pubmed: 3 5 2022
medline: 3 5 2022
Statut: epublish

Résumé

Malignant pleural mesotheliomas (MM) are known for their heterogenous histology and clinical behavior. MM histology reveals three major tumor cell populations: epithelioid, sarcomatoid, and biphasic. Using a dissecting approach, we showed that histochemical gradients help us better understand tumor heterogeneity and reconsider its histologic classifications. We also showed that this method to characterize MM tumor cell populations provides a better understanding of the underlying mechanisms for invasion and disease progression. In a cohort of 87 patients with surgically excised MM, we used hematoxylin and eosin to characterize tumor cell populations and Movat's pentachrome staining to dissect the ECM matrisome. Next, we developed a computerized semi-assisted protocol to quantify and reconstruct the ECM in 3D and examined the clinical association between the matricellular factors and patient outcome. Epithelioid cells had a higher matrix composition of elastin and fibrin, whereas, in the sarcomatoid type, hyaluronic acid and total collagen were most prevalent. The 3D reconstruction exposed the collagen I and III that form channels surrounding the neoplastic cell blocks. The estimated volume of the two collagen fractions was 14% of the total volume, consistent with the median estimated area of total collagen (12.05 mm Differential patterns in matricellular phenotypes in MM could be used in translational studies to improve patient outcome. More importantly, our data raise the possibility that cancer cells can use the matrisome for disease expansion and could be effectively targeted by anti-collagen, anti-elastin, and/or anti-hyaluronic acid therapies.

Sections du résumé

Background UNASSIGNED
Malignant pleural mesotheliomas (MM) are known for their heterogenous histology and clinical behavior. MM histology reveals three major tumor cell populations: epithelioid, sarcomatoid, and biphasic. Using a dissecting approach, we showed that histochemical gradients help us better understand tumor heterogeneity and reconsider its histologic classifications. We also showed that this method to characterize MM tumor cell populations provides a better understanding of the underlying mechanisms for invasion and disease progression.
Methods UNASSIGNED
In a cohort of 87 patients with surgically excised MM, we used hematoxylin and eosin to characterize tumor cell populations and Movat's pentachrome staining to dissect the ECM matrisome. Next, we developed a computerized semi-assisted protocol to quantify and reconstruct the ECM in 3D and examined the clinical association between the matricellular factors and patient outcome.
Results UNASSIGNED
Epithelioid cells had a higher matrix composition of elastin and fibrin, whereas, in the sarcomatoid type, hyaluronic acid and total collagen were most prevalent. The 3D reconstruction exposed the collagen I and III that form channels surrounding the neoplastic cell blocks. The estimated volume of the two collagen fractions was 14% of the total volume, consistent with the median estimated area of total collagen (12.05 mm
Conclusion UNASSIGNED
Differential patterns in matricellular phenotypes in MM could be used in translational studies to improve patient outcome. More importantly, our data raise the possibility that cancer cells can use the matrisome for disease expansion and could be effectively targeted by anti-collagen, anti-elastin, and/or anti-hyaluronic acid therapies.

Identifiants

pubmed: 35492318
doi: 10.3389/fmed.2022.871202
pmc: PMC9043486
doi:

Types de publication

Journal Article

Langues

eng

Pagination

871202

Informations de copyright

Copyright © 2022 Balancin, Baldavira, Prieto, Machado-Rugolo, Farhat, Assato, Velosa, Teodoro, Ab'Saber, Takagaki and Capelozzi.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Auteurs

Marcelo Luiz Balancin (ML)

Laboratory of Genomics and Histomorphometry, Department of Pathology, University of São Paulo Medical School (USP), São Paulo, Brazil.

Camila Machado Baldavira (CM)

Laboratory of Genomics and Histomorphometry, Department of Pathology, University of São Paulo Medical School (USP), São Paulo, Brazil.

Tabatha Gutierrez Prieto (TG)

Laboratory of Genomics and Histomorphometry, Department of Pathology, University of São Paulo Medical School (USP), São Paulo, Brazil.

Juliana Machado-Rugolo (J)

Laboratory of Genomics and Histomorphometry, Department of Pathology, University of São Paulo Medical School (USP), São Paulo, Brazil.
Health Technology Assessment Center (NATS), Clinical Hospital (HCFMB), Medical School of São Paulo State University (UNESP), Botucatu, Brazil.

Cecília Farhat (C)

Laboratory of Genomics and Histomorphometry, Department of Pathology, University of São Paulo Medical School (USP), São Paulo, Brazil.

Aline Kawassaki Assato (AK)

Laboratory of Genomics and Histomorphometry, Department of Pathology, University of São Paulo Medical School (USP), São Paulo, Brazil.

Ana Paula Pereira Velosa (APP)

Rheumatology Division of the Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo, FMUSP, São Paulo, Brazil.

Walcy Rosolia Teodoro (WR)

Rheumatology Division of the Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo, FMUSP, São Paulo, Brazil.

Alexandre Muxfeldt Ab'Saber (AM)

Laboratory of Genomics and Histomorphometry, Department of Pathology, University of São Paulo Medical School (USP), São Paulo, Brazil.

Teresa Yae Takagaki (TY)

Division of Pneumology, Instituto do Coração (Incor), University of São Paulo Medical School (USP), São Paulo, Brazil.

Vera Luiza Capelozzi (VL)

Laboratory of Genomics and Histomorphometry, Department of Pathology, University of São Paulo Medical School (USP), São Paulo, Brazil.

Classifications MeSH