scholarly journals MicroRNA ‐mediated extracellular matrix remodeling in squamous cell carcinoma of the oral cavity

Head & Neck ◽  
2021 ◽  
Author(s):  
Gilberto Mendes Menderico Junior ◽  
Thérèse Rachell Theodoro ◽  
Fatima Solange Pasini ◽  
Marina Menezes Ishikawa ◽  
Nayara Stephânie Sousa Santos ◽  
...  
2020 ◽  
Author(s):  
Gilberto Mendes Menderico ◽  
Thérèse Rachell Theodoro ◽  
Fatima Solange Pasini ◽  
Marina de Menezes Ishikawa ◽  
Nayara Stephânie Sousa Santos ◽  
...  

Abstract Background: It has been demonstrated that for oral cavity squamous cell carcinoma (SCC) as tumor thickness increases, there are lower rates of survival. Several molecular factors have been studied to determine this invasive behavior, including microRNAs, that play a role in the tumor microenvironment. Methods: The aim of this study is evaluate the role of extracellular matrix remodeling, as well as the involvement of microRNAs, in the process of oral cavity SCC carcinogenesis. This was a retrospective study with patients operated on for SCC of the oral cavity, in addition to a group of oral mucosa samples from paired patients. RNA extraction was performed, followed by complementary DNA amplification of microRNAs related to adhesion, migration, cell proliferation, apoptosis, and constituents of the extracellular matrix. We also performed immunohistochemical reactions for markers involved in the same biological processes. Results: High expression of miR-21-5p and miR-106-5p and low expression of miR-320a and miR-222-3p were predictors of malignancies and mir21-5p, individually, showed the best differentiation between the groups (AUC = 0.972). Regarding the immunohistochemical markers, there was greater expression of p53, EGFR, metalloproteinase-2 (MMP-2), laminin beta, Ki-67 and CD34 in the tumor cells than in the healthy mucosa. Furthermore, increased expression of MMP-2, metalloproteinase-9 (MMP-9), laminin alpha and laminin beta in tumor-related fibroblasts and lower continuity of type IV collagen in the basement membrane were observed. Conclusions: These results demonstrate the biological effects of microRNAs on the carcinogenesis of SCC of the oral cavity as well as the intense modification of the tumor microenvironment.


2018 ◽  
Author(s):  
Shun Yao ◽  
Xiangkun Han ◽  
Xinyuan Tong ◽  
Fuming Li ◽  
Zhen Qin ◽  
...  

AbstractLKB1 is frequently mutated in human non-small cell lung cancer (NSCLC) and Lkb1 deletion in mice triggered the lung adenocarcinoma (ADC) to squamous cell carcinoma (SCC) transdifferentiation (AST) through lysyl oxidase (LOX)-dependent extracellular matrix remodeling. Here we show that pharmacological inhibition of lysyl oxidase in KrasG12D/Trp53L/L mouse model, which is known to produce lung ADC only, triggers the ADC-to-SCC transdifferentiation independent of LKB1 status. Treatments of two different inhibitors of lysyl oxidase decrease collagen deposition and promote redox accumulation, and eventually trigger the AST. Importantly, these transited SCC show strong resistance to lysyl oxidase inhibition in stark contrast to ADC. Collectively, these findings establish a new AST mouse model independent of LKB1 inactivation status.


Author(s):  
Amrit Kaur Kaler, Shweta C, Smitha Chandra B.C, Rajeev Naik

Spindle cell carcinoma is a rare aggressive biphasic tumor, composed of neoplastic proliferation of both epithelial (squamous) and spindle cell population. It constitutes about 1% of all oral cavity tumors 2a and is almost rare on the tongue; only few cases have been reported so far. This variant of squamous cell carcinoma, comprises major diagnostic problems due to its varied histomorphology and resemblance to sarcomatous lesion; hence diligent screening and IHC markers are mandatory for its diagnosis.


2020 ◽  
Vol 25 (4) ◽  
pp. 287-294
Author(s):  
S. I. Kutukova ◽  
N. P. Beliak ◽  
G. A. Raskin ◽  
M. S. Mukhina ◽  
Yu. V. Ivaskova ◽  
...  

Relevance. Prognostic value of PD-L1 expression in oral cavity squamous cell carcinoma (OCSCC) and its effect on survival is still controversial. It should be to determine the prognostic role of PD-L1 expression on tumor and immune cells of OCSCC and assess their effect on overall survival (OS) and progression-free survival (PFS).Materials and methods. A prospective study included 145 patients, first diagnosed with OCSCC. PD-L1 expression on tumor and immune cells, infiltrating tumor and its microenvironment, was assessed in all tumor samples by IHC, CPS was calculated. Cut-off values were determined by ROC analysis for identification of PD-L1 expression effect on OS and PFS.Results. Most patients with oral mucosa squamous cell carcinoma showed positive expression of PD-L1 on tumor (77.2%) and immune cells (92.4%). The median PD-L1 expression on tumor cells was 13.5% [1.0-40.0], the median PD-L1 expression on immune cells was 5.0% [1.0-11.0], and the median CPS – 18.0 [3.0-7.8]. Univariate and multivariate analyses revealed a significant negative effect of PD-L1 expression on immune cells ≤ 7% on OS (HR 0.66; 95% CI 0.45-0.93; p = 0.0498); PD-L1 expression in tumor cells ≤ 15% (HR 0.65; 95% CI 0.43-0.98; p = 0.0416) and CPS ≤ 21 (HR 0.62; 95% CI 0.44-0.92; p = 0.0183) for PFS. PD-L1 expression in tumor cells ≤ 6% (HR 0.71; 95% CI 0.47-1.08; p = 0.1096) and CPS ≤ 7 (RR 0.67; 95% CI 0.44-1.01; p = 0.0575) had a confident tendency to negative impact on OS.Conclusion. Positive PD-L1 expression in tumor and immune cells as well as CPS are effective additional factors in the prognosis of the disease course, OS and PFS in patients with OCSCC.


Background: The objective of surgical management of oral squamous cell carcinoma (OSCC) is adequate resection with a clear margin. However, there is still a debate as to the optimal length for a mandibular resected margin. Objective: To examine the length of peri-neural spreading in T4 mandibular invaded oral cavity squamous cell carcinoma. Materials and Methods: Twenty-eight T4 pathological OSCC specimens that involved mandible and serial slices were studied and the length of tumor spreading along the inferior alveolar nerve (IAN) was determined. Tumor characteristics, risk factors, and survival were analyzed. Results: The incidence of peri-neural invasion was 11.11%, and IAN invasion was found in 14.29% of the tumor-invaded mandibular marrow. The length of tumor spreading along IAN was 3 to 12 mm. Poor prognostic factors of T4 OSCC were it being located on the tongue (HR 14.16), was pathological N2-3 (HR 31.05), and had high-risk features such as peri-neural invasion, lymphovascular invasion, and extra-nodal extension. Conclusion: A mandibular resected margin of at least 18 mm is recommended as a clear surgical margin in cases of T4 mandibular invasion OSCC. Keywords: Oral cancer, Perineural invasion, Inferior alveolar nerve, Squamous cell carcinoma, Mandibulectomy


2021 ◽  
Vol 41 (1) ◽  
pp. 163-167
Author(s):  
ARISTEIDIS CHRYSOVERGIS ◽  
VASILEIOS PAPANIKOLAOU ◽  
NICHOLAS MASTRONIKOLIS ◽  
DESPOINA SPYROPOULOU ◽  
MARIA ADAMOPOULOU ◽  
...  

1999 ◽  
Vol 23 (1) ◽  
pp. 45-56 ◽  
Author(s):  
Jozsef Piffko ◽  
Agnes Bankfalvi ◽  
Ulrich Joos ◽  
Dietmar Ofner ◽  
Melanie Krassort ◽  
...  

2021 ◽  
Vol 13 ◽  
pp. 175883592098406
Author(s):  
Vanesa Gutiérrez Calderón ◽  
Alexandra Cantero González ◽  
Laura Gálvez Carvajal ◽  
Yolanda Aguilar Lizarralde ◽  
Antonio Rueda Domínguez

Squamous cell carcinoma of oral cavity (OCSCC) accounts for approximately 25% of cases of head and neck squamous cell carcinoma (HNSCC). Tobacco and alcohol consumption are the main risk factors for both cancers. Surgical resection, combined with adjuvant radiotherapy or radiochemotherapy in patients with high risk of relapse, is the key element in management in the initial stages. However, despite the availability of aggressive multidisciplinary treatments, advanced resectable OCSCC carries poor prognosis; only half of the patients are disease-free 5 years after the surgery. Immunotherapy based on the use of immune checkpoint inhibitors has been proven to be effective in a wide variety of tumours, including recurrent and metastatic HNSCC. These positive results resulted in investigations into its effectiveness in earlier stages of the disease with OCSCC emerging as an interesting research model because of the accessible location of the tumours. This article reviews the potential advantages of emerging immunotherapeutic agents [mainly monoclonal antibodies against programmed cell death-1 ( PD-1) immune checkpoint inhibitors] as neoadjuvant treatment for OCSCC at locoregional stages as well as the ongoing clinical trials, challenges in evaluating tumour response, and possible predictive biomarkers of response with highlights regarding the role of oral microbiota as modulators of immune response. The efficacy and safety of anti- PD-1 drugs in these patients have been proven in preliminary trials. If there is a decrease in the relapse rate and an improvement in the overall survival after surgical resection in ongoing trials, preoperative immunotherapy may be established as a treatment option for patients with early stages of the disease.


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