Oral Tongue Squamous Cell Carcinoma Research Articles

Fluctuating role of antimicrobial peptide hCAP18/LL‑37 in oral tongue dysplasia and carcinoma.

Oral tongue squamous cell carcinoma (OTSCC), the most common cancer in the oral cavity, is aggressive and its incidence is increasing globally. Human host defense cationic antimicrobial peptide‑18/antimicrobial peptide leucine‑leucine‑37 (hCAP18/LL‑37) plays a complex role in various types of cancers. In the present study, we characterized the effects of exogenous LL‑37 on three OTSCC cell lines and determined the expression of hCAP18/LL‑37 in oral dysplastic and OTSCC patient samples. Our data revealed that LL‑37, especially in high doses, mostly reduced the proliferation of OTSCC cells, but the effect was fluctuating. However, LL‑37 stimulated the migration and invasion of OTSCC cells. The high dose of LL‑37 also increased the amount of total epidermal growth factor receptor (EGFR) probably due to stabilization of the receptor to the plasma membrane. However, activation of EGFR downstream pathways was mostly decreased. Our immunohistochemical analysis showed that the hCAP18/LL‑37 expression was higher in normal/mild dysplasia than in moderate/severe dysplasia and OTSCC. The hCAP18/LL‑37 expression did not correlate with clinicopathological features or outcome of OTSCC patients. Our data suggest that LL‑37 has a fluctuating effect on proliferation, migration and invasion of OTSCC cells, but it does not seem to play a role in the progression of OTSCC.

Characterization of the immune profile of oral tongue squamous cell carcinomas with advancing disease.

We investigated whether a unique immune response was instigated with the development of oral tongue squamous cell carcinomas (OTSCC), with/without nodal involvement, with/without recurrent metastatic disease, or within tumor involved nodes. One hundred and ten formalin‐fixed paraffin‐embedded samples were collected from a retrospective cohort of 67 OTSCC patients and 10 non‐cancerous tongue samples. Targets including CD4, CD8, FOXP3, PD‐L1, and PD‐1 were analyzed by immunohistochemistry. The Nanostring PanCancer Immune Profiling Panel was used for gene expression profiling. Data were externally validated in the The Cancer Genome Atlas (TCGA) head and neck (HNSCC), melanoma and lung squamous cell carcinoma (LSCC) cohorts. A 24‐immune gene signature was identified that discriminated more aggressive OTSCC cases, and although not prognostic in HNSCC was associated with survival in other TCGA cohorts (improved survival for melanoma, P < .001 and worse survival for LSCC, P = .038). OTSCC exhibited concordant gene and immunohistochemical (IHC) features characterized by a TH‐2 biased, proinflammatory profile with upregulated B cell and neutrophil gene activity and increased CD4, FOXP3, and PD‐L1 expression (P < .001 for all by IHC). Compared to less advanced disease, nodal involvement and recurrent OTSCC did not induce a different immune response although recurrent disease was characterized by significantly higher PD‐L1 expression (P = .004 by SP263, P = .013 by 22C3, P = .004 for gene expression). Identification of a gene signature associated with different prognostic effects in other cancers highlights common pathways of immune dysregulation that are impacted by the tumor origin. The significant immunosuppressive signaling in OTSCC indicates primary failure of immune system to control carcinogenesis emphasizing the need for early, combination therapeutic approaches.

Analyzing the factors that influence occult metastasis in oral tongue cancer.

ObjectivesWe accessed the various clinico-histopathological factors, and their association with occult metastasis (OM) in oral tongue squamous cell carcinoma (OTSCC).Materials and MethodsOne hundred-nine patients with OTSCC were divided into the elective neck dissection (END) group and the watchful waiting (WW) group. Age, sex, T-stage, depth of invasion and differentiation were evaluated to determine the correlation between clinico-histopathological factors and OM. For immunohistochemical analysis, paraffin-embedded blocks of 41 OTSCC specimens were examined with antibodies (VEGF-c, c-Met, and ROR1).ResultsThe group with tumor thickness of oral tongue cancer ≥3 mm had higher incidence of OM than those with a thickness of <3 mm. The depth of invasion was statistically correlated with OM (P=0.022). Immunohistochemical analysis showed that high expression of VEGF-c (P=0.043), c-Met (P=0.009), and ROR-1 (P=0.003) were statistically correlated with OM.ConclusionThe analysis of these clinico-histopathological and immunohistochemical factors can help to determine neck dissection in clinically negative (cN0) patients.

Squamous cell carcinoma of the oral tongue: Distinct epidemiological profile disease.

Oral squamous cell carcinoma (OSCC) occurs in different subsites within the oral cavity. Our goal was to investigate the epidemiological features of OSCC with relation to age and subsite. Retrospective review of all patients treated for OSCC in a tertiary care center between 2000 and 2018. A total of 360 patients were included. Five age groups were defined: 0 to 30, 31 to 45, 46 to 60, 61 to 75, and 76+. In the 0 to 30 and 31 to 45 groups, 94.6% of tumors originated in the oral tongue compared to 87%, 66%, and 61% in the 46 to 60, 61 to 75, and 76+ groups, respectively (P < .001). A higher proportion of oral tongue SCC (OTSCC) was found in nonsmokers (76% vs 62%, P = .02). In nonsmokers aged 0 to 60, 97.9% had OTSCC compared to 67.5% in the 61+ groups (P < .001). OSCC in young nonsmokers originates primarily in the tongue. The etiology of OTSCC in young patients may be different than other OSCC subsites and not related to smoking.

Tumor histologic grade as a risk factor for neck recurrence in patients with T1-2N0 early tongue cancer.

In current guidelines, early tongue cancer status post partial glossectomy without adverse risk features do not require adjuvant treatment. However, many of these patients developed recurrence with neck metastases soon. The objectives of this study were to investigate the potential risk factors in early tongue cancer that prophylactic management of neck may be considered. From January 2010 to September 2015, this retrospective study enrolled 102 patients with T1-2N0 primary oral tongue squamous cell carcinoma according to AJCC 8th edition Cancer Staging System. All patients underwent partial glossectomy with or without selective neck dissection, and did not receive any adjuvant treatment. Patients with any adverse risk features were excluded. We have studied the 4-year cancer-specific survival and neck recurrence rate, and analyzed the relevance between pathologic tumor classification, tumor depth, tumor histologic grade, and measured surgical margin of primary tumor. The median follow up duration was 47 months (range 6-93 months) with the median recurrence interval was 13 months. Histologic grade ≥2 of primary tumor was significantly associated with increased risk of neck recurrence and disease-specific mortality in both univariate and multivariate analysis. Histologic grade ≥2 was an adverse prognostic factor of neck recurrence and was significantly associated with poor cancer-specific survival in T1-2N0 early oral tongue cancer patients. Therefore, prophylactic neck dissection or prophylactic adjuvant radiation therapy to neck may be considered in T1-2N0 early oral tongue cancer with histologic grade ≥2 of primary tumor.

Sentinel lymph node biopsy for oral tongue squamous cell carcinoma cT1–2N0: prospective single-center study

The study objectiveis to evaluate the informativeness of the biopsy technique of the signal lymph node (LN) in squamous cell carcinoma of the tongue cT1–2N0.Materials and methods.A prospective, single-center study included 26 patients with morphologically verified squamous cell carcinoma of the tongue cT1–2 and the lack of clinical and radiological data for metastatic damage to the LNs of the neck. All patients underwent a radioisotope study of the lymphatic flow from the primary tumor and the topography of the signal LNs. The informativeness of the biopsy of the signal LNs was evaluated in accordance with 2 diagnostic models. When using the first diagnostic model, all LNs accumulating colloids labeled with the 99mTc isotope were considered signal LNs. In the second model, only nodes accumulating radiocolloids and located in the immediate vicinity of the primary tumor of the tongue and / or connected with the primary tumor by the “pathway” of the lymphatic vessels were considered as signal LNs.Results.The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy, according to the 1st diagnostic model, were 66.6 % (95 % confidence interval (CI) 9.43–99.16), 100 % (95 % CI 85.18–100 %), 100 %, 95.83 % (95 % CI 82.28–99.13 %), 96.15 % (95 % CI 80.36–99.90 %), and when all LNs located along with the signal LNs were removed at the same levels as regional LNs, the sensitivity increased to 100 %. In the second model, the diagnostic values were: 33.3 % (95 % CI 0.84–90.57), 100 % (95 % CI 85.18– 100.00), 100 %, 92 % (95 % CI 83.78–96.24), 92.31 % (95 % CI 74.87–99.05 %).Conclusion.Evaluation of lymphatic outflow from the primary tumor and assessment of sentinel lymph node location in patients with stage cT1–2N0M0 squamous cell carcinoma of the tongue allow a doctor to determine the volume of lymph node dissection for each patient individually. Unilateral lymph node dissection is acceptable in patients with unilateral lymphatic outflow, whereas in patients with bilateral lymphatic outflow, it is associated with a quite high (up to 10 %) risk of metastatic lesions in the lymph nodes on the opposite side of the neck. It is necessary to excise all lymph nodes accumulating radiocontrast agent and regional lymph nodes located at the same levels.

Analysis and classification of oral tongue squamous cell carcinoma based on Raman spectroscopy and convolutional neural networks

ABSTRACTTo detect oral tongue squamous cell carcinoma (OTSCC) using fibre optic Raman spectroscopy, we present a classification model based on convolutional neural networks (CNN) and support vector machines (SVM). 24 samples Raman spectra of OTSCC and para-carcinoma tissues from 12 patients were collected and analysed. In our proposed model, CNN is used as a feature extractor for forming a representative vector. Then the derived features are fed into an SVM classifier, which is used for OTSCC classification. Experimental results demonstrated that the area under the receiver operating characteristic curve was 99.96% and the classification error was zero (sensitivity: 99.54%, specificity: 99.54%). To show the superiority of this model, comparison results with the state-of-the-art methods showed it can obtain a competitive accuracy. These findings may pay a way to apply the proposed model in the fibre optic Raman instruments for intra-operative evaluation of OTSCC resection margins.

Assessment of TLR4 and TLR9 signaling and correlation with human papillomavirus status and histopathologic parameters in oral tongue squamous cell carcinoma

Toll-like receptors (TLRs) may promote or inhibit tumor progression. The aim of this study was to assess the expression of TLR4 and TLR9 and their downstream targets in oral tongue squamous cell carcinoma (OTSCC) in correlation with histopathologic parameters and human papillomavirus (HPV) status. OTSCC (fully or superficially invasive and in situ) were studied. Immunohistochemical expression of TLR4, TLR9, nuclear factor-κΒ (NF-κΒ/p65), and interferon-β (IFN-β) was evaluated in tumor and inflammatory cells and in adjacent morphologically normal mucosa. HPV status was also determined. TLR4 showed increased expression levels in tumor and infiltrating inflammatory cells compared with adjacent mucosa, especially in fully invasive cases; a negative correlation between TLR4 levels in inflammatory cells and tumor grade was observed. TLR9 was upregulated in tumor and infiltrating inflammatory cells compared with the adjacent mucosa; its expression in inflammatory cells was higher in well differentiated tumors. NF-κΒ and IFN-β were elevated in cancerous tissues, especially in fully invasive cases, and positively correlated with TLR4 and/or TLR9. HPV positivity (detected in 15.9% of the cases) demonstrated positive correlation with TLR9 and NF-κΒ levels. TLR4 and TLR9 are upregulated in OTSCC and its microenvironment and, by affecting important downstream molecules, such as NF-κB and IFN-β, may play a role in oral cancer development and progression.

Oral Tongue Squamous Cell Carcinoma in Young, Non-Smoking, and Non-Drinking Patients

Smoking, alcohol, and old age are known risk factors for oral tongue squamous cell carcinoma (OTSCC). While OTSCC in nonsmoking and nondrinking young patients has been described as having an aggressive phenotype, risk factors and oncological outcomes of this cancer are poorly understood. The purpose of this study was to characterize outcomes of OTSCC in young, non-smoking, non-drinking patients compared to older patients.

Expression of RAD51 and Its Clinical Impact in Oral Squamous Cell Carcinoma.

Purpose To examine the expression of RAD51 in oral squamous cell carcinoma (OSCC) and analyze its connection with pathological grade, clinical stage, and lymphatic metastasis potential. Methods For this study, 74 OSCC samples, 15 normal mucosa tissues, and 11 normal skin tissue samples were collected. RAD51 expression was investigated using immunohistochemistry. A follow-up visit was used to assess the prognosis of each patient. We compared RAD51 expression in oral mucosa epithelial cells (OMECs), keratinocytes, and tongue squamous cell carcinoma cells (TSCCs) by Western blot analysis. Results RAD51 expression was higher in tumor cells than in normal mucosal tissues. In addition, RAD51 expression was associated with higher tumor differentiation (P < 0.05). Also, RAD51 expression was higher (P < 0.05). Also, RAD51 expression was higher (P < 0.05). Also, RAD51 expression was higher (Conclusion A strong positive correlation was found between RAD51 expression and the degree of malignancy in OSCC patients, suggesting that RAD51 could be an excellent prognostic indicator for OSCC patients.

Usefulness of contrast-enhanced CT in the evaluation of depth of invasion in oral tongue squamous cell carcinoma: comparison with MRI.

There is currently no standardized approach for assessing the depth of invasion (DOI) of oral tongue squamous cell carcinoma via diagnostic imaging. We investigated the usefulness of contrast-enhanced computed tomography (CECT) for estimating the pathological DOI of oral tongue squamous cell carcinoma by evaluating the correlation of pathological DOI with the DOIs on CECT and magnetic resonance imaging (MRI). We retrospectively reviewed 21 of 139 patients who underwent radical surgery for primary oral tongue squamous cell carcinoma between 2009 and 2018. The 21 cases were evaluable, without dental artifacts on CECT. DOIs on CECT and MRI, and pathological DOI were measured. The median pathological DOI was 9mm, that on CECT was 10.9mm, that on T2-weighted MRI was 14.2mm, and that on contrast-enhanced T1-weighted MRI was 13.1mm. The DOIs on CECT and on MRI were larger than the pathological DOI (p = 0.003 to < 0.001). The absolute value of the difference between pathological DOI and DOI on CECT was smaller than that between pathological DOI and DOI on MRI (p = 0.01 and 0.003). DOIs on CECT and on MRI correlated with pathological DOI (r = 0.74-0.66, all p < 0.001). Spearman's correlation coefficient between DOI on CECT and pathological DOI was greater than that between DOI on MRI and pathological DOI. Compared to the DOI determined on an MRI scan, the DOI determined on a CECT scan correlated with and better approximated pathological DOI. Therefore, CECT can be useful for preoperative staging of patients with oral tongue squamous cell carcinoma.

The promise of immunotherapy in the treatment of young adults with oral tongue cancer.

Historically considered a disease of the older male resulting from cumulative tobacco and alcohol use, more recently we have witnessed a rise in the global incidence of oral tongue squamous cell carcinoma in younger adults, particularly those without any identifiable risk factor exposure. These patients appear to be at higher overall risk for locoregional treatment failure and often experience a more heterogeneous clinical course, with some afflicted with particularly aggressive, rapidly progressive disease. Recent research efforts have supported the idea that although this disease may be genomically similar in these groups, and molecular differences in the tumor immune microenvironment may account for biological differences between young and older patients, as well as patients with and without exposure to alcohol or tobacco. In this review, we seek to summarize current knowledge regarding pathogenesis of oral tongue carcinoma in the young adult patient and examine the potential role of the immune response in disease progression and as a target for novel immunotherapies.

Limonin suppresses the progression of oral tongue squamous cell carcinoma via inhibiting YAP transcriptional regulatory activity

The suppressive roles of limonin have been established in various tumors. However, its roles in oral tongue squamous cell carcinoma (OTSCC) progression are still confusing. This work aims to explore limonin-mediated effects on OTSCC progression. CCK8 analysis was performed to evaluate limonin-mediated effects on OTSCC cell viability. Wound healing and transwell invasion analysis were constructed to examine the effects of limonin on OTSCC cell migration and invasion capacity. RT-qPCR, western blot and luciferase reporter assays were used to explore the underlying mechanisms contributing to limonin-mediated effects on OTSCC progression. It was found that limonin significantly suppressed the viability of OTSCC cells. Additionally, limonin reduced the migration and invasion ability of OTSCC cells. Mechanistically, limonin suppresses OTSCC progression by promoting the nuclear to cytoplasm translocation of YAP, decreasing YAP protein expression and subsequently decreasing YAP transcriptional regulatory activity, this is responsible for limonin-mediated suppression on OTSCC progression. Thus, this work suggests that limonin suppresses OTSCC progression through inhibiting YAP transcriptional regulatory activity.

Homologous-targeting biomimetic nanoparticles for photothermal therapy and Nrf2-siRNA amplified photodynamic therapy against oral tongue squamous cell carcinoma

Photothermal therapy (PTT) and photodynamic therapy (PDT) have some advantages such as site selectivity, non- or little-invasive property and negligible drug resistance for treatment of oral tongue squamous cell carcinoma (OTSCC). However, the activation of intracellular antioxidant responses will partly counteract anticancer effects of PDT. As a well-known redox-regulated transcription factor, Nrf2 has been found to participate in the resistance of tumor cells against PDT. Hereon, a biomimetic nanoparticle system was designed for co-loading and targeted delivery of photosensitizer indocyanine green (ICG) and Nrf2-siRNA, thus hope to achieve synergistic effects of PTT and amplified PDT in OTSCC. Poly(β-amino ester) (PBAE)/poly lactic-co-glycolic acid (PLGA) blended nanoparticles co-loaded with ICG and Nrf2-siRNA were prepared and then encapsulated within the vesicles of cancer cell membrane (CCM) specifically derived from homologous OTSCC, thus obtained biomimetic nanoparticles named as M@PPI-siRNA. Both in vitro and in vivo, M@PPI-siRNA nanoparticles exhibited strong OTSCC-targeting ability due to tumor-homing effect of homologous CCM. Upon laser irradiation at 808 nm, M@PPI-siRNA nanoparticles significantly down-regulated the expressions of Nrf2 and its regulated genes, glutamate-cysteine ligase catalytic subunit (GCLC) and modifier subunit (GCLM) that play important roles in ROS detoxification, and subsequently indirectly enhanced PDT anticancer effects by maintaining the accumulation of intracellular ROS. Through cooperation of PTT and Nrf2-siRNA amplified PDT, M@PPI-siRNA nanoparticles significantly inhibited the proliferation and induced the apoptosis of OTSCC cells, and also notably suppressed tumor growth and angiogenesis in OTSCC tumor-bearing mice. In summary, this study provides a promising OTSCC-targeted delivery system for both photosensitizer and gene, and also confirms that Nrf2-siRNA is an efficient synergist for amplifying PDT.

Anatomically-based transoral surgical approach to early-stage oral tongue squamous cell carcinoma.

The mainstream of treatment of early-stage oral tongue squamous cell carcinoma (OTSCC) is represented by transoral resection with "adequate" free margins. Despite that, a precise and shared definition of "adequate margin" is lacking, and so is a standardized transoral surgical technique.The tongue is a symmetrically paired organ, consisting of intertwining intrinsic and extrinsic muscles, which can be distinguished during dissection. Routes of tumoral spread in oral tongue cancer are well-known and should be taken into account during resection. We propose herein a standardized and replicable surgical technique to resect early-stage OTSCC, based on rational anatomical considerations.

Intra-Operative Ultra-Sonography for Assessment of Adequate Resection Margin in Primary Squamous Cell Carcinoma of Tongue: A Feasible Study with Early Experience

Background: The completeness of surgical resection of oral tongue squamous cell carcinoma with a margin of microscopically 5-mm is the standard of care. Deep resection margin status and tumour thickness are important factors for loco-regional recurrence and survival. Adequacy of deep margins by palpation method is usually underestimated resulting in greater normal tissue loss which requires tongue reconstruction. Intra-operative intraoral ultrasound assessment of tumor thickness outlines the adequate resection margins which would minimize the risk of microscopic close margin as well as excessive normal tissue loss. We report our early experience of estimation of deep resection margins with help of ultrasound in oral tongue cancers.

Artesunate targets oral tongue squamous cell carcinoma via mitochondrial dysfunction-dependent oxidative damage and Akt/AMPK/mTOR inhibition.

Although mitochondrial metabolism has recently gained attention as a promising therapeutic strategy in cancer, little is known on the impact of mitochondrial respiration inhibition on oral tongue squamous cell carcinoma (OTSCC). Using in vitro and in vivo OTSCC models, our work demonstrates that inducing mitochondrial dysfunction by anti-malarial drug artesunate is effective in targeting OTSCC stem-cell like and bulk cells. Artesunate inhibits anchorage-independent colony formation, proliferation and survival in all tested OTSCC cell lines although with varying efficacy. Artesunate displays preferential anti-OTSCC activity by sparing normal cells. Mechanism analysis indicates that artesunate inhibits mitochondrial respiration via suppressing mitochondrial complex I and II but not IV or V, resulting in oxidative stress and damage. Interestingly, OTSCC cells that are more sensitive to artesunate have higher level of basal mitochondrial respiration and reversed respiratory capacity compared to those with less sensitivity to artesunate, suggesting the varying dependence on mitochondrial respiration among OTSCC cell lines. In addition, artesunate induces oxidative stress and damage in cells with low sensitivity to a less extent than in those with high sensitivity. We confirm that mitochondrial respiration inhibition is required for the action of artesunate in OTSCC. Mitochondrial dysfunction by artesunate further activates AMPK and suppresses Akt/mTOR. Importantly, the in vitro observations are reproducible in vivo OTSCC xenograft mouse model. Our findings provide pre-clinical evidence on the efficacy of artesunate and emphasize the therapeutic value of targeting mitochondrial respiration in OTSCC.

Downregulation of lncRNA HOTTIP Suppresses the Proliferation, Migration, and Invasion of Oral Tongue Squamous Cell Carcinoma by Regulation of HMGA2-Mediated Wnt/β-Catenin Pathway.

Background: Oral tongue squamous cell carcinoma (OTSCC) is a common type of oral tumor. LncRNAs (long noncoding RNAs) and miRNAs (microRNAs) were identified as regulators in many human cancers. This study aims to explore the molecular basis of HOXA transcript at the distal tip (HOTTIP) in regulating OTSCC progression. Materials and Methods: The expression of HOTTIP, miR-124-3p, and high-mobility group AT-hook 2 (HMGA2) was detected by quantitative real-time polymerase chain reaction. Next, the proliferation was evaluated by 3-(4,5-dimethylthiazole-2-y1)-2,5-biphenyl tetrazolium bromide (MTT) assay. The migration and invasion were assessed by transwell assay. Furthermore, dual-luciferase reporter assay was performed to confirm the combination between HOTTIP and miR-124-3p, miR-124-3p, and HMGA2. Protein levels of HMGA2, β-catenin, c-Myc, and E-cadherin were examined by Western blot. The nude mice model was employed to test the tumor growth in vivo. Results: HOTTIP was upregulated in OTSCC tissues and cells, and was highly expressed in positive lymph node metastasis and late-stage OTSCC patients. Silencing HOTTIP impeded proliferation, migration, and invasion of OTSCC cells. Moreover, HOTTIP knockdown inhibited proliferation, migration, and invasion of OTSCC cells by targeting miR-124-3p. Besides, miR-124-3p targeted HMGA2 to block proliferation, migration, and invasion. HMGA2 could rescue the inhibitory effects of HOTTIP interference on proliferation, migration, and invasion. In addition, HMGA2 overexpression reversed the downregulation of β-catenin and c-Myc protein levels and upregulation of E-cadherin level affected by HOTTIP silencing. Finally, HOTTIP silencing repressed tumor growth and resulted in a great rise on miR-124-3p and E-cadherin expression and a distinct fall on HMGA2, β-catenin, and c-Myc protein levels. Conclusions: HOTTIP knockdown restrained proliferation, migration, and invasion of OTSCC cells by miR-124-3p/HMGA2 axis through Wnt/β-catenin pathway.

Immunohistochemical expression of DNA repair proteins in oral tongue and lower lip squamous cell carcinoma

The DNA repair system involves genes and proteins that are essential for the maintenance of genome integrity and the consequent control of various cellular processes. Alterations in these genes and proteins play a role in tumor development and progression and might be associated with prognosis. The aims of this study were to analyze the immunoexpression of two DNA repair proteins, XPF and XRCC1, in lower lip squamous cell carcinoma (LLSCC) and oral tongue squamous cell carcinoma (OTSCC), and to investigate possible associations with clinical and histopathological parameters. The immunohistochemical expression of XPF and XRCC1 was analyzed semi-quantitatively in 40 cases each of LLSCC and OTSCC. The chi-squared test or Fisher's exact test, when appropriate, was used to investigate the association between expression of the proteins and clinicopathological characteristics. The cytoplasmic immunoexpression of XPF was high in OTSCC (95% of the cases analyzed) but low in LLSCC (52.5%). Among the clinicopathological parameters evaluated, a statistically significant association was observed between high nuclear expression of XRCC1 and the absence of regional lymph node metastasis in patients diagnosed with OTSCC (p=0.006). The high protein expression of XPF and XRCC1 in OTSCC and LLSCC suggests an important role in the development and progression of these tumors. Our study found an association between high nuclear expression of XRCC1 and the absence of loco-regional metastasis in cases diagnosed as OTSCC, suggesting a role of this protein in tumor progression.

FoxP3+ regulatory T cells in oral tongue squamous cell carcinoma in young and older patients.

Regulatory T (Treg) cells can suppress antitumor immune response, but little is known about possible age-related differences in the number of these cells in the microenvironment of oral tongue squamous cell carcinoma (OTSCC). The aim of this study was to determine the number of FoxP3+ Treg cells in the microenvironment of OTSCC in young (≤ 45 years) and older (≥ 60 years) patients, and to correlate the findings with clinicopathological parameters (sex, tumor size/extent, regional lymph node metastasis, clinical staging, and histopathological grade of malignancy). Forty-eight OTSCCs (24 diagnosed in young patients and 24 diagnosed in older patients) were selected. Lymphocytes exhibiting nuclear immunopositivity for FoxP3 were quantified at the tumor invasive front and the results were analyzed statistically using the non-parametric Mann-Whitney test. FoxP3+ lymphocytes were observed in all cases assessed. The number of FoxP3+ lymphocytes in OTSCC tended to be higher in older patients (p = 0.055). Analysis of OTSCC in males and in early clinical stages revealed a higher number of Treg cells in older patients than in young ones (p < 0.05). In older patients, the number of Treg cells tended to be higher in smaller tumors (p = 0.079). Tumors with intense inflammatory infiltrate exhibited a larger number of Treg cells, both in young (p = 0.099) and older patients (p = 0.005). The results suggest a greater participation of Treg cells in immunoinflammatory responses in the microenvironment of OTSCC in older patients, particularly in males and in early stages.