Oral Tongue Squamous Cell Carcinoma Research Articles

Intraoral Ultrasound versus MRI for Depth of Invasion Measurement in Oral Tongue Squamous Cell Carcinoma: A Prospective Diagnostic Accuracy Study

Oral squamous cell carcinoma (OSCC) of the tongue is the most common type of oral cavity cancer, and tumor depth of invasion (DOI) is an important prognostic factor. In this study, we investigated the accuracy of intraoral ultrasound and magnetic resonance imaging (MRI) for assessing DOI in patients with OSCC. Histopathological measurement of DOI was used as a reference standard. We conducted a prospective study including patients planned for surgical treatment of OSCC in the tongue. The DOI was measured in an outpatient setting by intraoral ultrasound and MRI, and was compared to the histopathological DOI measurements. Bland–Altman analysis compared the mean difference and 95% limits of agreement (LOA) for ultrasound and MRI, and the Wilcoxon signed-rank test was used to test for significance. The correlation was evaluated using Pearson’s correlation coefficient. We included 30 patients: 26 with T1 or T2 tumors, and 4 with T3 tumors. The mean difference from histopathology DOI was significantly lower for ultrasound compared to MRI (0.95 mm [95% LOA −4.15 mm to 6.06 mm] vs. 1.90 mm [95% LOA −9.02 mm and 12.81 mm], p = 0.023). Ultrasound also led to significantly more correct T-stage classifications in 86.7% (26) of patients compared to 56.7% (17) for MRI, p = 0.015. The Pearson correlation between MRI and histopathology was 0.57 (p < 0.001) and the correlation between ultrasound and histopathology was 0.86 (p < 0.001). This prospective study found that intraoral ultrasound is more accurate than MRI in assessing DOI and for the T-staging of oral tongue cancers. Clinical practice and guidelines should implement intraoral ultrasound accordingly.

Investigation of Roles of SLC38A1 in Proliferation and Differentiation of Mouse Tongue Epithelium and Expression in Human Oral Tongue Squamous Cell Carcinoma.

The aerobic glycolytic pathway, boosting lactate formation, and glutamine addiction are two hallmarks of cancer pathophysiology. Consistent with this, several cell membrane glutamine transporters, belonging to different solute carrier (SLC) families, have been shown to be upregulated in a cell-specific manner to furnish the cells with glutamine and glutamine-derived metabolic intermediates. Among them, the system A transporter Slc38a1 has a higher affinity for glutamine compared to other SLC transporters, and it undergoes highly multifaceted regulation at gene and protein levels. The current study aimed to investigate the functional role of Slc38a1 in the proliferation and maturation of the mouse tongue epithelium. Secondly, we aimed to examine the expression of SLC38A1 and its regulation in human tongue oral squamous cell carcinoma (OTSCC). Employing Slc38a1 wild-type and knockout mice, we showed that Slc38a1 was not directly linked to the regulation of the proliferation and differentiation of the mouse tongue epithelium. External transcriptomic datasets and Western blot analyses showed upregulation of SLC38A1 mRNA/protein in human OTSCC and oral cancer cell lines as compared to the corresponding controls. Further, an investigation of external datasets indicated that mechanisms other than the amplification of the SLC38A1 chromosomal locus or hypomethylation of the SLC38A1 promoter region might be important for the upregulation of SLC38A1 in OTSCC.

Single-cell RNA sequencing reveals the heterogeneity of epithelial cell and fibroblast cells from non- to metastatic lymph node OTSCC.

Lymph node metastasis (LNM) is one of the common features of oral tongue squamous cell carcinoma (OTSCC). LNM is also taken as a sign of advanced OTSCC and poor survival rate. Recently, single-cell RNA sequencing has been applied in investigating the heterogeneity of tumor microenvironment and discovering the potential biomarkers for helping the diagnosis and prognosticating. Pathogenesis of LNM in OTSCC remains unknown. Specifically, cancer-associated fibroblasts (CAFs) and epithelial tumor cells could foster the progression of tumors. Thus, in this study, we aimed to comprehensively analyze the roles of subpopulations of CAFs and epithelial tumor cells in lymph node metastatic OTSCC using the integration of OTSCC single-cell RNA sequencing datasets. Four distinct subtypes of CAFs, namely vascular CAFs, myofibroblast CAFs, inflammatory CAFs, and growth arrest CAFs were successfully discovered in LNM tumor and confirmed the roles of GAS and PTN pathways in the progression of tumor metastasis. In addition, NKAIN2+ epithelial cells and FN1+ epithelial cells specifically exhibited an upregulation of PTN, NRG, MIF, and SPP1 signaling pathways in the metastatic OTSCC. In doing so, we put forth some potential biomarkers that could be utilized for the purpose of diagnosing and prognosticating OTSCC during its metastatic phase and tried to confirm by immunofluorescence assays.

PDGF-BB accelerates TSCC via fibroblast lactates limiting miR-26a-5p and boosting mitophagy

The tumor microenvironment and cancer-associated fibroblasts (CAFs) play crucial roles in tumor development, and their metabolic coupling remains unclear. Clinical data showed a positive correlation between PDGF-BB, CAFs, and glycolysis in the tumor microenvironment of oral tongue squamous cell carcinoma patients. In vitro, CAFs are derived from hOMF cells treated with PDGF-BB, which induces their formation and promotes aerobic glycolysis. Mitophagy increased the PDGF-BB-induced formation of CAF phenotypes and aerobic glycolysis, while autophagy inhibition blocked PDGF-BB-induced effects. Downregulation of miR-26a-5p was observed in CAFs; upregulation of miR-26a-5p inhibited the expression of mitophagy-related proteins ULKI, Parkin, PINK1, and LC3 and aerobic glycolysis in PDGF-BB-induced CAFs. PDGF-BB-induced CAFs promoted tumor cell proliferation, invasion, metastasis, NF-κB signaling pathway activation, and PDGF-BB secretion. Thus, PDGF-BB is associated with lactate-induced CAF formation and glucose metabolism reprogramming. These findings indicate potential therapeutic targets in oral tongue squamous cell carcinoma.

Utility of Diffusion-weighted MR Imaging for Evaluating the Depth of Invasion in Oral Tongue Squamous Cell Carcinoma.

The 8th edition of the American Joint Committee on Cancer staging system included the depth of invasion (DOI) for the T classification of oral cancer. However, no standardized method has been established to clinically measure the DOI. This study aimed to investigate the accuracy of MRI-based DOI for oral tongue squamous cell carcinoma (OTSCC) in each MRI sequence. We enrolled 49 patients with histologically proven OTSCC, treated surgically between April 2017 and February 2021. We divided the DOI into three groups using 5 and 10 mm, the thresholds for determining the T stage, and retrospectively evaluated the agreement between MRI-based DOI and pathological DOI (pDOI) for each MRI sequence, axial T1-weighted imaging (T1WI), T2-weighted imaging with fat suppression (FS-T2WI), contrast-enhanced T1WI with fat suppression (CE-T1WI), diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC) maps. We also divided the DOI into two groups using 3 mm, the threshold for considering elective neck dissection, and evaluated the overestimation rate of MRI-based DOI in lesions with pDOI ≤ 3 mm. With 5-mm and 10-mm divisions, the accuracy of the DOI assessment was highest on DWI (0.82, weighted kappa = 0.85). With a 3-mm division, the accuracy was also highest on DWI (0.87, kappa = 0.73). The overestimation rate of the MRI-based DOI in lesions with pDOI ≤ 3 mm was lowest on DWI (27.8%). DOI on DWI exhibits a comparatively higher rate of concordance with pDOI. DWI may be more useful than other MRI sequences in evaluating the DOI of OTSCC.

Retraction: KIF18A is a potential prognostic factor and promotes tumor progression in oral tongue squamous cell carcinoma

Retraction: KIF18A is a potential prognostic factor and promotes tumor progression in oral tongue squamous cell carcinoma

Prognostic Value of Anteroposterior Extension in Oral Tongue and Floor Squamous Cell Carcinoma

The tongue and oral floor represent the most involved subsite by oral cancer, and there are no reported systems to classify anteroposterior tumor extension with prognostic effect. In other cancers, the anterior vs posterior tumor extension is a relevant prognostic factor. To establish whether anterior vs posterior tumor extension may represent a prognostic factor in oral tongue and floor squamous cell carcinoma (OTFSCC). This was a retrospective cohort study of patients who underwent surgery for OTFSCC from January 1, 2010, to December 31, 2021, at 2 tertiary-level academic institutions in Italy (University of Padua and University of Brescia). Patients eligible for the study had histologically proven primary OTFSCC; underwent surgery-based, curative treatment; and had available preoperative contrast-enhanced imaging. Four anatomical lines were designed to assess tumor extension: (1) chin-palate line (CPL), (2) chin-basion line, (3) Stensen duct line, and (4) lingual septum line. Preoperative imaging was re-evaluated, and tumor extension was classified as either anterior or posterior according to the lines. Overall survival and time to recurrence (TTR) were evaluated according to tumor extension. These outcomes were reported as 5-year survival rates with 95% CIs. Of the 133 patients included, 79 (59.4%) were male, and the mean (SD) age was 62.7 (15.4) years. The 5-year TTR difference was higher for posterior vs anterior OTFSCC classified according to CPL (21.0%; 95% CI, 8.3%-33.7%), Stensen duct line (15.5%; 95% CI, 1.0%-30.0%), and lingual septum line (17.2%; 95% CI, 2.2%-32.3%). Overall survival analysis showed similar results. At the multivariable analysis on TTR, N status (adjusted hazard ratio [HR], 3.0; 95% CI, 1.2-7.1) and anteroposterior classification according to CPL (adjusted HR, 7.1; 95% CI, 0.9-54.6) were the variables associated with the highest adjusted HRs. In this cohort study, OTFSCC with a posterior extension to the CPL was associated with a higher risk of recurrence and death. This analysis suggests that the poor prognosis conveyed by the posterior tumor extension is independent of other relevant prognosticators except for the burden of nodal disease. This estimate is not precise and does not allow for definitive clinically important conclusions; therefore, further prospective studies are necessary to confirm these data.

Machine learning based on magnetic resonance imaging and clinical parameters helps predict mesenchymal-epithelial transition factor expression in oral tongue squamous cell carcinoma: a pilot study

ObjectivesThis study aimed to develop machine learning models to predict phosphorylated mesenchymal-epithelial transition factor (p-MET) expression in oral tongue squamous cell carcinoma (OTSCC) using magnetic resonance imaging (MRI)-derived texture features and clinical features. MethodsThirty-four patients with OTSCC were retrospectively collected. Texture features were derived from preoperative MR images, including T2WI, apparent diffusion coefficient mapping, and contrast-enhanced (ce)-T1WI. Dimension reduction was performed consecutively with reproducibility analysis and an information gain algorithm. Five machine learning methods—AdaBoost, logistic regression (LR), naïve Bayes (NB), random forest (RF), and support vector machine (SVM)—were adopted to create models predicting p-MET expression. Their performance was assessed with fivefold cross-validation. ResultsIn total, 22 and 12 cases showed low and high p-MET expression, respectively. After dimension reduction, 3 texture features (ADC-Minimum, ce-T1WI-Imc2, and ce-T1WI-DependenceVariance) and 2 clinical features (depth of invasion [DOI] and T-stage) were selected with good reproducibility and best correlation with p-MET expression levels. The RF model yielded the best overall performance, correctly classifying p-MET expression status in 87.5% of OTSCCs with an area under the receiver operating characteristic curve of 0.875. ConclusionDifferences in p-MET expression in OTSCCs can be noninvasively reflected in MRI-based texture features and clinical parameters. Machine learning can potentially predict biomarker expression levels, such as MET, in patients with OTSCC.

The modified Polsby-Popper score, a novel quantitative histomorphological biomarker and its potential to predict lymph node positivity and cancer-specific survival in oral tongue squamous cell carcinoma.

The significance of different histological spreading patterns of tumor tissue in oral tongue squamous cell carcinoma (TSCC) is well known. Our aim was to construct a numeric parameter on a continuous scale, that is, the modified Polsby-Popper (MPP) score, to describe the aggressiveness of tumor growth and infiltration, with the potential to analyze hematoxylin and eosin-stained whole slide images (WSIs) in an automated manner. We investigated the application of the MPP score in predicting survival and cervical lymph node metastases as well as in determining patients at risk in the context of different surgical margin scenarios. We developed a semiautomated image analysis pipeline to detect areas belonging to the tumor tissue compartment. Perimeter and area measurements of all detected tissue regions were derived, and a specific mathematical formula was applied to reflect the perimeter/area ratio in a comparable, observer-independent manner across digitized WSIs. We demonstrated the plausibility of the MPP score by correlating it with well-established clinicopathologic parameters. We then performed survival analysis to assess the relevance of the MPP score, with an emphasis on different surgical margin scenarios. Machine learning models were developed to assess the relevance of the MPP score in predicting survival and occult cervical nodal metastases. The MPP score was associated with unfavorable tumor growth and infiltration patterns, the presence of lymph node metastases, the extracapsular spread of tumor cells, and higher tumor thickness. Higher MPP scores were associated with worse overall survival (OS) and tongue carcinoma-specific survival (TCSS), both when assessing all pT-categories and pT1-pT2 categories only; moreover, higher MPP scores were associated with a significantly worse TCSS in cases where a cancer-free surgical margin of <5 mm could be achieved on the main surgical specimen. This discriminatory capacity remained constant when examining pT1-pT2 categories only. Importantly, the MPP score could successfully define cases at risk in terms of metastatic disease in pT1-pT2 cancer where tumor thickness failed to exhibit a significant predictive value. Machine learning (ML) models incorporating the MPP score could predict the 5-year TCSS efficiently. Furthermore, we demonstrated that machine learning models that predict occult cervical lymph node involvement can benefit from including the MPP score. We introduced an objective, quantifiable, and observer-independent parameter, the MPP score, representing the aggressiveness of tumor growth and infiltration in TSCC. We showed its prognostic relevance especially in pT1-pT2 category TSCC, and its possible use in ML models predicting TCSS and occult lymph node metastases.

The application of radiomics machine learning models based on multimodal MRI with different sequence combinations in predicting cervical lymph node metastasis in oral tongue squamous cell carcinoma patients.

The purpose of this study was to explore preliminary the performance of radiomics machine learning models based on multimodal MRI to predict the risk of cervical lymph node metastasis (CLNM) for oral tongue squamous cell carcinoma (OTSCC) patients. A total of 400 patients were enrolled in this study and divided into six groups according to the different combinations of MRI sequences. Group I consisted of patients with T1-weighted images (T1WI) and FS-T2WI (fat-suppressed T2-weighted images), group II consisted of patients with T1WI, FS-T2WI, and contrast enhanced MRI (CE-MRI), group III consisted of patients with T1WI, FS-T2WI, and T2-weighted images (T2WI), group IV consisted of patients with T1WI, FS-T2WI, CE-MRI, and T2WI, group V consisted of patients with T1WI, FS-T2WI, T2WI, and apparent diffusion coefficient map (ADC), and group VI consisted of patients with T1WI, FS-T2WI, CE-MRI, T2WI, and ADC. Machine learning models were constructed. The performance of the models was compared in each group. The machine learning model in group IV including T1WI, FS-T2WI, T2WI, and CE-MRI presented best prediction performance, with AUCs of 0.881 and 0.868 in the two sets. The models with CE-MRI performed better than the models without CE-MRI(I vs. II, III vs. IV, V vs. VI). The radiomics machine learning models based on CE-MRI showed great accuracy and stability in predicting the risk of CLNM for OTSCC patients.

Evaluation of the presence of Th1 response through T-bet and IFN-gamma immunohistochemical expression in lower lip and oral tongue squamous cell carcinomas

IntroductionEvaluate the immunohistochemical expression of T-bet and IFN-γ in lower lip (LLSCC) and oral tongue squamous cell carcinoma (OTSCC), verifying the presence of Th1 responses in lesions with different clinical conditions. Methods and materialsThirty OTSCC and 30 LLSCC were analyzed by immunohistochemistry. T-bet was quantitatively assessed by parenchyma cell and stroma quantification, and IFN-γ was semi-quantitatively analyzed: 1:0–25%; 2:26–50%; 3:51–75%; 4:> 75% immunopositive cells. Histological differentiation degrees were categorized as well differentiated (WD), moderately differentiated (MD), or poorly differentiated (PD). ResultsOTSCC presented the highest number of T-bet+, parenchyma (p: 0.006), stroma (p: 0.156), parenchyma/stroma (p: 0.015), with no relationship to histological malignancy grade. IFN-γ higher concentrations in LLSCC were detected in parenchyma, stroma and in parenchyma/stroma (p: 0.000), as well as greater immunoreactivity in WD and MD (p: 0.001). In OTSCC, a positive and statistically significant correlation was observed between T-bet+ in parenchyma and IFN-γ in stroma(r: 0.388; p: 0.034), in addition to a statistically significant positive correlation between T-bet in parenchyma compared to stroma(r: 0.411; p: 0.024) and for IFN-γ in both parenchyma and stroma(r: 0.775; p: 0.000) in LLSCC. Higher T-bet+ was observed in OTSCCs, although higher IFN-γ was detected in LLSCCs. ConclusionThus, we suggest that, even though LLSCC presented lower T-bet+, the favorable microenvironment in these lesions led to an expressive activation of IFN-γ by T-bet+, considerably acting on Th1 differentiation and in antitumor activity, which, admittedly, present less aggressive behavior, reinforcing once again the important role of this cytokine and its use in strategy to fight cancer.

Detecting recurrent disease and surgical outcomes in patients with locally advanced tongue cancer after multimodal treatment using ¹⁸F-FDG-PET/CT

The purpose of this study was to evaluate the utility of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (FPCT) parameters for detecting recurrent disease and the outcomes of salvage surgery in patients with locally advanced oral tongue squamous cell carcinoma (TSCC) after multimodal treatment. In total, 69 patients with locally advanced TSCC were treated with multimodal therapy. All patients underwent whole-body FPCT scans 4–10 months after the initial surgery. The analysis included FPCT parameters, such as maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Histological examination was used as the reference standard. Patients with recurrent TSCC underwent salvage surgery or surgery plus systemic treatment. This study included 69 patients: 36 in the recurrent TSCC group and 33 in the non-recurrent TSCC group. The SUVmax, MTV, and TLG in the recurrent TSCC group were 11.3 ± 3.6, 28.3 ± 15.6 cm3, and 113.2 ± 46.8 g, respectively; these values were 5.9 ± 3.6, 5.1 ± 2.2 cm3, and 13.4 ± 4.8 g, in the non-recurrent TSCC group respectively. The two groups had significant differences in terms of SUVmax, MTV, and TLG. In the recurrent TSCC group, 91.6 % of patients presented with local, locoregional, and regional disease and underwent salvage surgery plus systemic therapy, whereas 8.4 % had locoregional recurrence with distant metastases alone and underwent surgery plus systemic therapy. The patients were followed up for 12–60 months; 19 and 20 patients in the recurrent and non-recurrent TSCC groups showed no evidence of disease, whereas 11 and 8 were alive with the disease. Local recurrence or distant metastases led to the deaths of six patients in the recurrent TSCC group and five in the non-recurrent TSCC group. No significant differences in survival were observed between the two groups. FPCT parameters can detect the recurrence of locally advanced TSCC after multimodal treatment. Early salvage surgery can improve the treatment outcomes for recurrent TSCC.

Evaluation of micrometastasis and isolated tumor cells in node-negative early-stage oral tongue squamous cell carcinoma: a cross-sectional study in tertiary-level hospitals in eastern India

The present study aimed to investigate the incidence of micrometastasis (MMs) and isolated tumor cells (ITCs) in node-negative early-stage oral tongue squamous cell carcinoma (T1-T2 N0). The secondary objective was to correlate the incidence with the clinicopathologic parameters of age, sex, depth of invasion, pattern of invasion, host lymphocytic response, and size and grade of primary tumor. Micrometastasis and ITCs in cervical nodes of 30 patients with early-stage oral tongue squamous cell carcinoma were detected and compared using 3 methods: routine hematoxylin and eosin staining, serial-sectioning at intervals of 150 microns employing hematoxylin and eosin, and serial sectioning pan-cytokeratin immunostaining. Associations with clinicopathological variables were analyzed. Metastatic tumor cells were detected in the cervical nodes of 2 patients using serial sectioning and immunohistochemistry, resulting in upstaging of 6.6% of all cases. Level I and II lymph nodes were primarily involved. Early-stage oral tongue squamous cell carcinoma has a significant potential for MMs that frequently go undetected in routine histopathologic examination. However, laborious and technique-sensitive, serial sectioning in combination with pan-cytokeratin staining (AE1/AE3) may aid in detecting MMs and ITCs in patients with early-stage OTSCC.

Depth of Invasion: Influence of the Latest TNM Classification on the Prognosis of Clinical Early Stages of Oral Tongue Squamous Cell Carcinoma and Its Association with Other Histological Risk Factors.

The American Joint Committee on Cancer (AJCC), in its 8th edition, introduces modifications to the previous TNM classification, incorporating tumour depth of invasion (DOI). The aim of this research is to analyse the prognosis (in terms of disease-free survival and overall survival) of clinical early stage (I and II) squamous cell carcinomas of the oral tongue according to the DOI levels established by the AJCC in its latest TNM classification to assess changes to the T category and global staging system and to evaluate the association between DOI and other histological risk factors. A retrospective longitudinal observational study of a series of cases was designed. All patients were treated with upfront surgery at our institution between 2010 and 2019. The variables of interest were defined and classified into four groups: demographic, clinical, histological and evolutive control. Univariate and multivariate analyses were carried out and survival functions were calculated using the Kaplan-Meier method. Statistical significance was established for p values below 0.05. Sixty-one patients were included. The average follow-up time was 47.42 months. Fifteen patients presented a loco-regional relapse (24.59%) and five developed distant disease (8.19%). Twelve patients died (19.67%). Statistically significant differences were observed, with respect to disease-free survival (p = 0.043), but not with respect to overall survival (p = 0.139). A total of 49.1% of the sample upstaged their T category and 29.5% underwent modifications of their global stage. The analysis of the relationship between DOI with other histological variables showed a significant association with the presence of pathological cervical nodes (p = 0.012), perineural invasion (p = 0.004) and tumour differentiation grade (p = 0.034). Multivariate analysis showed association between depth of invasion and perineural invasion. Depth of invasion is a histological risk factor in early clinical stages of oral tongue squamous cell carcinoma. Depth of invasion impacts negatively on patient prognosis, is capable per se of modifying the T category and the global tumour staging, and is associated with the presence of cervical metastatic disease, perineural invasion and tumoural differentiation grade.

Impact of dysplasia at resection margin on oncologic outcome after curative resection of oral tongue squamous cell carcinoma: significance of high-grade dysplastic resection margin.

This study aimed to compare the oncologic outcomes among negative, close, positive, and dysplasia resection margins (RMs) with oral tongue squamous cell carcinoma (OSCC) and to investigate the impact of dysplastic RMs. The 565 patients were retrospectively analyzed and divided into four groups according to RM. Dysplasia was classified into mild, moderate, and severe subgroups. RMs consisted of negative (62.1%), close (27.1%), positive (2.1%), and dysplastic (8.7%). In multivariate analysis, advanced T/N stages and positive RM were significant risk factors for overall survival, while dysplasia at the RM was not a significant risk factor for locoregional recurrence or overall survival. In subgroup analysis of patients with dysplastic margin, RM with severe dysplasia showed higher recurrence than mild and moderate dysplasia. Dysplastic RM was not a risk factor for recurrence and survival. Severe dysplasia RM should be carefully observed due to higher recurrence compared to other dysplasia RMs.

Silencing of heat shock factor 1 (HSF1) inhibits proliferation, invasion, and epithelial-mesenchymal transition in oral squamous cell carcinoma.

Oral squamous cell carcinoma is characterized by high rates of morbidity and mortality. Evidence obtained for different types of cancer shows that tumor initiation, progression, and therapeutic resistance are regulated by heat shock factor 1. This research aimed to analyze the effects of heat shock factor 1 on the biological behavior of oral squamous cell carcinoma. Clinicopathological and immunoexpression study of heat shock factor 1 in 70 cases of oral tongue SCC and functional assays by gene silencing of this factor in an oral tongue SCC cell line. Heat shock factor 1 was overexpressed in oral tongue SCC specimens compared to normal oral mucosa (p < 0.0001) and in the SCC15 line compared to immortalized keratinocytes (p < 0.005). No significant associations were observed between overexpression of heat shock factor 1 and clinicopathological parameters or survival rates of the oral tongue SCC cases in the present sample. In vitro experiments showed that heat shock factor 1 silencing inhibited cell proliferation (p < 0.005) and cell cycle progression, with the accumulation of cells in the G0/G1 phase (p < 0.01). In addition, heat shock factor 1 silencing reduced cell invasion capacity (p < 0.05) and epithelial-mesenchymal transition, characterized by a decrease in vimentin expression (p < 0.05) and an increase in E-cadherin expression (p < 0.001). Heat shock factor 1 may exert several functions that help maintain cell stability under the stressful conditions of the tumor microenvironment. Thus, strategies targeting the regulation of this protein may in the future be a useful therapeutic tool to control the progression of oral squamous cell carcinoma.

Immunoexpression of HSP27 does not seem to influence the prognosis of oral tongue squamous cell carcinoma.

New methods of early detection and risk assessment have been studied aiming to predict the prognosis of patients and directing a specialized treatment of the oral tongue squamous cell carcinoma (OTSCC). In this context, several molecular biomarkers have been investigated for this purpose, and, among them, the heat shock protein 27 (HSP27) can be named. The study aimed to analyze whether heat shock protein 27 (HSP27) exerts any influence on OTSCC, correlating its immunoexpression with clinicopathological parameters, and patient survival. The sample comprised 55 OTSCC cases and 20 normal oral mucosa specimens. The malignancy grading systems proposed by the WHO in 2005, Brandwein-Gensler et al., and Almangush et al. were applied in a histomorphological study. HSP27 expressions were evaluated through the Immunoreactivity Score System (IRS). Significant values were considered at p <0.05 for all statistical tests. Higher IRS results were observed for normal oral mucosa specimens when compared to OTSCC cases (p <0.001). No significant associations between HSP27 immunostaining, the analyzed clinicopathological parameters and patient survival were observed. The results of the present study indicate lower HSP27 expression in OTSCC cases compared to normal oral mucosa specimens. Thus, HSP27 expression does not seem to influence patient prognosis.

Impact of Age, Race, and Gender on the Association Between Marital Status and Treatment Outcomes in Oral Tongue Squamous Cell Carcinomas.

Background: The objective of this study is to assess whether the impact of marital status on oral tongue squamous cell carcinomas (OTSCC) prognosis varied by gender, age, and race. Methods: We examined the clinicopathological variables using chi-squared tests, and we evaluated the association between survival and different variables using the methods of Kaplan-Meier. Univariate and multivariate analyses were performed to determine the effects of each variable on survival. Results: A total of 5282 patients were analyzed. The rate of being married was higher among Asian or Caucasian, and this rate decreased with higher tumor stage. While both married male and female survivors benefit from their marital status, we found a differential in OS based on gender, with females benefiting more than males (male P = .038; female P = .009, respectively). Patients who were divorced/separated/widowed (male HR = 1.275, 95% CI: 1.085-1.499; female HR = 1.313, 95% CI: 1.083-1.593) and never married (male HR = 1.164, 95% CI: 0.983-1.378; female HR = 1.224, 95% CI: 0.958-1.565) had increased hazard of OS compared with married/partnered patients (male P = .038; female P = .009). Subgroups analysis shows that the effect of marital status was significantly associated with treatment outcome only in Caucasian patients aged 50 years or older who harbored non-metastatic disease and received surgery (P < .001). Conclusion: While there are survival benefits for married patients with OTSCC, married/partnered females may benefit more than males. Age, race, and gender could affect the correlation between marital status and survival.

Lymph Node Ratio as a Prognostic Factor for Oral Tongue Squamous Cell Carcinoma: A Retrospective Study.

Background Oral squamous cell carcinoma (OSCC) incidence and its mortality have increased recently. The oral part of the tongue is one of the commonest sites for OSCC. Apart from Tumour-Node-Metastasis (TNM) staging, lymph node ratio (LNR) has been implicated as one of the useful predictors for the better clinical outcome of the disease. The aim of the present study was to assess the LNR as a prognostic factor for patients having oral tongue squamous cell carcinoma (OTSCC). Materials and methods It is a retrospective study of 122 patients with OTSCC who were managed primarily by surgery with curative intent from January 2014 to December 2016. The mean lymph node ratio was measured and compared with various parameters of clinical outcome such as five-year overall survival (OS), five-year disease-free survival (DFS), locoregional failure (LRF) within three years, and distant metastasis (DM) within five years using Kruskal-Wallis Test followed by Mann-Whitney Post Hoc Test. The association of LNR with other tumor characteristic features like perineural invasion, extra-nodal extension (ENE), and histopathological grading was also elicited. Results The study population's mean age was 50.5 ± 11.77 years. Among them, 85 were males and 37 were females.On comparingthe mean LNR value with patient status after primary treatment, the patients with minimal LNR value had statistically significant five-year OS and five-year DFS (p< 0.001). High mean LNR values were associated with other adverse features like perineural invasion and ENE, which were statistically significant (p<0.001). Receiver operator characteristics (ROC) curve analysis for the LNR parameter for determining the cut-off (0.02) between OS and DFS had 86% sensitivity and 40% specificity. Conclusion The LNR could be an important prognosis factor for OTSCC that helps in determining better clinical outcomes.

Novel human lymph node-derived matrix supports the adhesion of metastatic oral carcinoma cells

Background3D culture is increasingly used in cancer research, as it allows the growth of cells in an environment that mimics in vivo conditions. Metastases are the primary cause of morbidity and mortality in cancer patients, and solid tumour metastases are mostly located in lymph nodes. Currently, there are no techniques that model the pre-metastatic lymph node microenvironment in vitro. In this study, we prepared a novel extracellular matrix, Lymphogel, which is derived from lymph nodes, mimicking the tumour microenvironment (TME) of metastatic carcinoma cells. We tested the suitability of the new matrix in various functional experiments and compared the results with those obtained using existing matrices.MethodsWe used both commercial and patient-derived primary and metastatic oral tongue squamous cell carcinoma (OTSCC) cell lines. We characterized the functional differences of these cells using three different matrices (human uterine leiomyoma-derived Myogel, human pre-metastatic neck lymph node-derived Lymphogel (h-LG), porcine normal neck lymph node-derived Lymphogel (p-LG) in proliferation, adhesion, migration and invasion assays. We also performed proteomic analyses to compare the different matrices in relation to their functional properties.ResultsOTSCC cells exhibited different adhesion and invasion patterns depending on the matrix. Metastatic cell lines showed improved ability to adhere to h-LG, but the effects of the matrices on cell invasion fluctuated non-significantly between the cell lines. Proteomic analyses showed that the protein composition between matrices was highly variable; Myogel contained 618, p-LG 1823 and h-LG 1520 different proteins. The comparison of all three matrices revealed only 120 common proteins. Analysis of cellular pathways and processes associated with proteomes of each matrix revealed similarities of Myogel with h-LG but less with p-LG. Similarly, p-LG contained the least adhesion-related proteins compared with Myogel and h-LG. The highest number of unique adhesion-related proteins was present in h-LG.ConclusionsWe demonstrated that human pre-metastatic neck lymph node-derived matrix is suitable for studying metastatic OTSCC cells. As a whole-protein extract, h-LG provides new opportunities for in vitro carcinoma cell culture experiments.