University of Oulu

Marilena Vered, Anna Shnaiderman-Shapiro, Ginette Schiby, Ayelet Zlotogorski-Hurvitz, Tuula Salo, Ran Yahalom, Markers of the pre-metastatic niche "knock on the door" of metastasis-free cervical lymph nodes in patients with oral cancer, Acta Histochemica, Volume 121, Issue 8, 2019, 151447, ISSN 0065-1281,

Markers of the pre-metastatic niche “knock on the door” of metastasis-free cervical lymph nodes in patients with oral cancer

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Author: Vered, Marilena1,2; Shnaiderman-Shapiro, Anna1; Schiby, Ginette2;
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, The 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, 0.3 MB)
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Language: English
Published: Elsevier, 2019
Publish Date: 2020-09-27


Aim: To assess expression of some markers of the pre-metastatic niche (PMN) in lymph nodes (LNs) of oral cancer patients.

Methods: LNs from metastatic-free neck dissections (LN0/N0, N = 43) and metastatic-free LNs in the vicinity of metastasis-containing LNs (LN0/N+, N = 30) were immuno-histochemically stained for lysyl oxidase (LOX), fibronectin (FN), vascular-endothelial growth factor receptor (VEGFR)-1 and matrix metalloproteinase (MMP)-9. Staining was assessed as 0 (no or weak staining), 1 (strong stain in 25% cells or extracellular area), 2 (same as 1 but in up to 50%) and 3 (same as 1 but in > than 50% of cells/area). Assessment was performed in the lymph node capsule (CAP), sub-capsular sinus (SCS) and medullary sinus (MS). In addition, sections were stained with picrosirius red and examined with polarized microscopy for assessing the distribution of polarization colors of the collagen fibers in the LN capsular area.

Results: All examined LNs were positive for markers of the PMN. In general, the distribution and intensity of the immunoreactivity was similar between the LN0/N0 and LN0/N+, with only a few differences regarding expression of LOX in the capsule (p = 0.002) and VEGFR1 and MMP9 in the SCS (p = 0.023 and p < 0.001, respectively). Picrosirius red stain and polarized microscopy revealed a disrupted arrangement and distribution of the collagen fibers in both LN0/N0 and LN0/N + .

Conclusion: Markers for PMN were shown for the first time to be expressed in cervical LN0/N0 from patients with oral cancer, suggesting the increased permissive pathway remotely paved by the primary oral tumor for the incoming metastatic cells.

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Series: Acta histochemica
ISSN: 0065-1281
ISSN-E: 1618-0372
ISSN-L: 0065-1281
Volume: 121
Issue: 8
Article number: 151447
DOI: 10.1016/j.acthis.2019.151447
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Funding: The study was supported by the Ernest and Tova Turnheim Clinical Research Fund in Dentistry, 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