University of Oulu

Marilena Vered, Anna Shnaiderman-Shapiro, Ayelet Zlotogorski-Hurvitz, Tuula Salo, Ran Yahalom, Cancer-associated fibroblasts in the tumor microenvironment of tongue carcinoma is a heterogeneous cell population, Acta Histochemica, Volume 121, Issue 8, 2019, 151446, ISSN 0065-1281,

Cancer-associated fibroblasts in the tumor microenvironment of tongue carcinoma is a heterogeneous cell population

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Author: Vered, Marilena1,2; Shnaiderman-Shapiro, Anna1; Zlotogorski-Hurvitz, Ayelet1,3;
Organizations: 1Dept. Oral Pathology, Oral Medicine and Oral Radiology, School of Dental Medicine, Tel Aviv University, Tel Aviv, Israel
2Institute of Pathology, The Chaim Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
3Dept. Oral and Maxillofacial Surgery, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel
4Cancer and Translational Research Unit, University of Oulu and MRC, Oulu University Hospital, Oulu, Finland
5Oral and Maxillofacial Diseases, Clinicum, University of Helsinki, Helsinki, and HUSLAB, Helsinki University Hospital, Helsinki, Finland
6Dept. Oral and Maxillofacial Surgery, The Chaim Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
Format: article
Version: accepted version
Access: open
Online Access: PDF Full Text (PDF, 0.2 MB)
Persistent link:
Language: English
Published: Elsevier, 2019
Publish Date: 2020-10-08


Objectives: To examine different immunophenotypes of cancer-associated fibroblasts (CAFs) in tongue squamous cell carcinoma (TSCC) and to investigate how they related to clinical outcomes.

Methods: Serial sections from 54 cases of TSCC were immunohistochemically stained with α-smooth muscle actin (αSMA, CAF marker) to determine CAF density, and double-immunostained with αSMA combined with CD80 and CD86 (myeloid/monocytic-derived cell markers), Nanog (mesenchymal stem cell marker) and CD133 (hematopoietic/endothelial stem cell marker). Density of cells co-expressing these marker combinations was semi-quantitatively assessed in 5 randomly selected high power fields within the tumor area and scored as 1 — one-to-five stained cells in each field, 2 — more than 5 stained cells in each field; any finding less than score 1, was allocated a score of 0.

Results: There were 26 CAF-poor, 16 CAF-rich and 12 CAF-intermediated cases. CD86⁺αSMA⁺ cells were the most frequent (80.4%) followed by CD80⁺αSMA⁺ (72%) and Nanog⁺αSMA⁺ cells (56%). The CD133⁺αSMA⁺ phenotype was found only in association with blood vessels. High density of αSMA⁺ CAFs was associated with disease recurrence and poor survival (p < 0.05). Increased density of CD86⁺αSMA⁺ cells was significantly associated with CAF-rich tumors and with poor survival (p < 0.05).

Conclusions: In TSCC, CAFs demonstrate heterogeneous and overlapping phenotypes with the myeloid/monocytic type being the most frequent and having an impact on the clinical outcomes. Further studies are needed in order to further characterize CAF phenotypes in carcinomas of various oral sites, as this may open new frontiers for personalized medicine.

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Series: Acta histochemica
ISSN: 0065-1281
ISSN-E: 1618-0372
ISSN-L: 0065-1281
Volume: 121
Issue: 8
Article number: 151446
DOI: 10.1016/j.acthis.2019.151446
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Funding: The study was supported in part by the Lefcoe Fund for Dental Research, Tel Aviv University. The funding source was not scientifically involved in the study.
Copyright information: © 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license