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Special Issue "Pathogenesis and Therapy of Oral Carcinogenesis"

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 31 March 2023 | Viewed by 3297

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Special Issue Editors

Dr. Marko Tarle

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Guest Editor

1. Department of Maxillofacial Surgery, Dubrava University Hospital, 10 000 Zagreb, Croatia
2. School of Dental Medicine, University of Zagreb, 10 000 Zagreb, Croatia
Interests: oral cancer; head and neck cancer; cancer therapy; molecular biomarkers; maxillofacial surgery

Prof. Dr. Ivica Lukšić

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Guest Editor

1. Department of Maxillofacial Surgery, Dubrava University Hospital, 10 000 Zagreb, Croatia
2. School of Medicine, University of Zagreb, 10 000 Zagreb, Croatia
Interests: oral cancer; head and neck cancer; cancer therapy; molecular biomarkers; maxillofacial surgery; salivary gland tumors

Special Issue Information

Dear Colleagues,

Despite the development of diagnostic and therapeutic strategies in recent decades, oral squamous cell carcinoma (OSCC) has a high morbidity and mortality (less than 50%), and represents a major challenge for scientists and clinicians. Although the oral cavity is readily accessible for clinical examination, in 2020, 377,713 people worldwide were diagnosed with lip and oral cancer, while 177,757 people died from it, with a trend toward increasing numbers of patients younger than 50 years of age. Preventive oral screening for high-risk patients and the detection, monitoring and treatment of oral potentially malignant disorders (OPMD) such as oral leukoplakia (OL) and oral erythroplakia (OE) are essential for the prevention of OSCC. New biomarkers for OPMD that indicate a high risk of malignant transformation need to be identified, and the approach to the treatment and follow-up of these patients needs to be modified, as does the development of drugs that reduce the progression of genetic changes in apparently healthy mucosa.

The shortcomings of histopathologic classification systems in predicting the malignant transformation of OPMD and the survival prognosis of patients with OSCC motivate us to explore the complex molecular pathways involved in the development of oral cavity cancer and its spread to regional lymph nodes and distant organs.

In this Special Issue, we encourage the publication of research and review articles addressing the various molecular mechanisms involved in the different steps of oral carcinogenesis that could serve as diagnostic biomarkers and therapeutic targets.

Dr. Marko Tarle
Prof. Dr. Ivica Lukšić
Guest Editors

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Keywords

oral cancer
oral premalignant disorders
tumor microenvironment
molecular biomarkers
targeted therapy
oral tumorigenesis

Published Papers (4 papers)

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Research

Open AccessArticle

Nuclear Epidermal Growth Factor Receptor Overexpression as a Survival Predictor in Oral Squamous Cell Carcinoma

and

Int. J. Mol. Sci. 2023, 24(6), 5816; https://doi.org/10.3390/ijms24065816 - 18 Mar 2023

Viewed by 188

Abstract

The aim of this study was to determine, by immunohistochemical methods, the expression of nEGFR and markers of cell proliferation (Ki-67), cell cycle (mEGFR, p53, cyclin D1), and tumor stem cells (ABCG2) in 59 pathohistological samples of healthy oral mucosa, 50 oral premalignant changes (leukoplakia and erythroplakia), and 52 oral squamous cell carcinomas (OSCC). An increase in the expression of mEGFR and nEGFR was found with the development of the disease (p < 0.0001). In the group of patients with leukoplakia and erythroplakia, we found a positive correlation between nEGFR and Ki67, p53, cyclin D1, and mEGFR, whereas in the group of patients with OSCC, we found a positive correlation between nEGFR and Ki67, mEGFR (p < 0.05). Tumors without perineural (PNI) invasion had a higher expression of p53 protein than tumors with PNI (p = 0.02). Patients with OSCC and overexpression of nEGFR had shorter overall survival (p = 0.004). The results of this study suggest a potentially important independent role of nEGFR in oral carcinogenesis. Full article

(This article belongs to the Special Issue Pathogenesis and Therapy of Oral Carcinogenesis)

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Open AccessArticle

Potential of uPAR, αvβ6 Integrin, and Tissue Factor as Targets for Molecular Imaging of Oral Squamous Cell Carcinoma: Evaluation of Nine Targets in Primary Tumors and Metastases by Immunohistochemistry

, Kirstine Karnov,

Anne-Marie Kanstrup Fiehn

Andreas Kjaer

and

Christian von Buchwald

Int. J. Mol. Sci. 2023, 24(4), 3853; https://doi.org/10.3390/ijms24043853 - 14 Feb 2023

Viewed by 458

Abstract

No clinically approved tumor-specific imaging agents for head and neck cancer are currently available. The identification of biomarkers with a high and homogenous expression in tumor tissue and minimal expression in normal tissue is essential for the development of new molecular imaging targets in head and neck cancer. We investigated the expression of nine imaging targets in both primary tumor and matched metastatic tissue of 41 patients with oral squamous cell carcinoma (OSCC) to assess their potential as targets for molecular imaging. The intensity, proportion, and homogeneity in the tumor and the reaction in neighboring non-cancerous tissue was scored. The intensity and proportion were multiplied to obtain a total immunohistochemical (IHC) score ranging from 0–12. The mean intensity in the tumor tissue and normal epithelium were compared. The expression rate was high for the urokinase-type plasminogen activator receptor (uPAR) (97%), integrin αvβ6 (97%), and tissue factor (86%) with a median total immunostaining score (interquartile range) for primary tumors of 6 (6–9), 12 (12–12), and 6 (2.5–7.5), respectively. For the uPAR and tissue factor, the mean staining intensity score was significantly higher in tumors compared to normal epithelium. The uPAR, integrin αvβ6, and tissue factor are promising imaging targets for OSCC primary tumors, lymph node metastases, and recurrences. Full article

(This article belongs to the Special Issue Pathogenesis and Therapy of Oral Carcinogenesis)

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Open AccessCommunication

Is CCL2 an Important Mediator of Mast Cell–Tumor Cell Interactions in Oral Squamous Cell Carcinoma?

and

Int. J. Mol. Sci. 2023, 24(4), 3641; https://doi.org/10.3390/ijms24043641 - 11 Feb 2023

Viewed by 482

Abstract

In this study, we aimed to evaluate the influence of interactions between mast cells (MCs) and oral squamous cell carcinoma (OSCC) tumor cells on tumor proliferation and invasion rates and identify soluble factors mediating this crosstalk. To this end, MC/OSCC interactions were characterized using the human MC cell line LUVA and the human OSCC cell line PCI-13. The influence of an MC-conditioned (MCM) medium and MC/OSCC co-cultures on the proliferative and invasive properties of the tumor cells was investigated, and the most interesting soluble factors were identified by multiplex ELISA analysis. LUVA/PCI-13 co-cultures increased tumor cell proliferation significantly (p = 0.0164). MCM reduced PCI-13 cell invasion significantly (p = 0.0010). CC chemokine ligand 2 (CCL2) secretion could be detected in PCI-13 monocultures and be significantly (p = 0.0161) increased by LUVA/PCI-13 co-cultures. In summary, the MC/OSCC interaction influences tumor cell characteristics, and CCL2 could be identified as a possible mediator. Full article

(This article belongs to the Special Issue Pathogenesis and Therapy of Oral Carcinogenesis)

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Open AccessCommunication

Positive Linear Relationship between Nucleophosmin Protein Expression and the Viral Load in HPV-Associated Oropharyngeal Squamous Cell Carcinoma: A Possible Tool for Stratification of Patients

Marco D’Agostino

Marco Di Cecco

Carla Marani

Maurizio Giovanni Vigili

Sara Sileno

Chiara Costanza Volpi

and

Int. J. Mol. Sci. 2023, 24(4), 3482; https://doi.org/10.3390/ijms24043482 - 09 Feb 2023

Viewed by 465

Abstract

Most oropharyngeal squamous cell carcinomas (OPSCCs) are human papillomavirus (HPV)-associated, high-risk (HR) cancers that show a better response to chemoradiotherapy and are associated with improved survival. Nucleophosmin (NPM, also called NPM1/B23) is a nucleolar phosphoprotein that plays different roles within the cell, such as ribosomal synthesis, cell cycle regulation, DNA damage repair and centrosome duplication. NPM is also known as an activator of inflammatory pathways. An increase in NPM expression has been observed in vitro in E6/E7 overexpressing cells and is involved in HPV assembly. In this retrospective study, we investigated the relationship between the immunohistochemical (IHC) expression of NPM and HR-HPV viral load, assayed by RNAScope in situ hybridization (ISH), in ten patients with histologically confirmed p16-positive OPSCC. Our findings show that there is a positive correlation between NPM expression and HR-HPV mRNA (Rs = 0.70, p = 0.03), and a linear regression (r² = 0.55; p = 0.01). These data support the hypothesis that NPM IHC, together with HPV RNAScope, could be used as a predictor of transcriptionally active HPV presence and tumor progression, which is useful for therapy decisions. This study includes a small cohort of patients and, cannot report conclusive findings. Further studies with large series of patients are needed to support our hypothesis. Full article

(This article belongs to the Special Issue Pathogenesis and Therapy of Oral Carcinogenesis)

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Special Issue "Pathogenesis and Therapy of Oral Carcinogenesis"

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