Cases Of Oral Tongue Squamous Cell Carcinoma Research Articles

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.

Clinical significance of L1CAM expression and its biological role in the progression of oral squamous cell carcinoma.

L1 cell adhesion molecule (L1CAM) has been implicated in the progression and metastasis of numerous cancers. However, the role of L1CAM in oral squamous cell carcinoma (OSCC) is not well characterized. In the present study, the expression of L1CAM was examined in oral tongue squamous cell carcinoma (OTSCC) tissue samples by immunohistochemistry, the clinicopathological significance of L1CAM expression was evaluated by chi‑squared test, and the overall survival (OS) rate was analyzed using Kaplan‑Meier method according to the expression of L1CAM. In addition, it was aimed to elucidate the biological role of L1CAM and the underlying molecular mechanisms by which L1CAM functions in OSCC cells in relation to epithelial‑mesenchymal transition (EMT) and PI3K/AKT/ERK signaling pathways. Thus, the functions of L1CAM on the OSCC cell proliferation, migration and invasion, and the activation of EMT and PI3K/AKT/ERK signaling pathways were investigated invitro. Positive L1CAM expression was found in 32.5% of OTSCC cases and was significantly correlated with high histologic grade, greater depth of invasion, lymph node metastasis, perineural invasion, advanced stage, and survival status. Patients with positive L1CAM expression had significantly lower OS rate. Particularly in patients with early OTSCC, L1CAM expression was strongly associated with worse prognosis. Overexpression of the recombinant human L1CAM protein significantly increased cell proliferation, migration and invasion. By contrast, L1CAM knockdown using small interfering RNA significantly inhibited cell proliferation, migration, invasion and EMT. Moreover, phosphorylated (p)‑PI3K, p‑AKT and p‑ERK expression levels were significantly reduced by L1CAM knockdown. Taken together, the findings of the present study suggested that L1CAM could be a potential prognostic marker and a promising therapeutic target in OSCC.

TUMOR BUDDING IN ORAL TONGUE SQUAMOUS CELL CARCINOMA BETWEEN YOUNGER AND OLDER INDIVIDUALS: A MORPHOLOGICAL STUDY

<h3>Objectives</h3> To morphologically analyze tumor budding (TB) in cases of oral tongue squamous cell carcinoma (OTSCC) between younger (<45 years-old) and older (≥45 years-old) individuals, correlating them with clinical parameters. <h3>Study Design</h3> The sample consisted of 60 cases of OTSCC, divided in 2 groups (30 cases in younger individuals and 30 cases in older individuals). Clinical parameters (harmful habits, tumor size, lymph node metastasis, distant metastasis, clinical staging, management, outcome, and survival) were obtained from medical records. Morphologically, TB was classified using 3 scores: absence, presence of <15 focus, and ≥15 focus. Statistical analysis employed Fischer's exact test, with <i>P</i> < .05. <h3>Results</h3> There was a significant difference in harmful habits (<i>P</i> = .049), distant metastasis (<i>P</i> = .020), and clinical staging (<i>P</i> = .024) between younger and elderly individuals. TB was present in 63.3% of the sample (<i>n</i> = 38), predominantly with <15 focus, with no significant difference between age groups. There was no significant association of TB with any of the morphologic parameters. <h3>Conclusions</h3> It is suggested that OTSCC in older individuals is diagnosed in later clinical stages and with distant metastasis. TB is observed in OTSCC, independent of age group.

Stage-Specific Survival in Young Patients With Oral Tongue Squamous Cell Carcinoma.

To determine demographic factors and clinicopathologic characteristics associated with survival in young patients (age <45 years) with early- (I-II) or late-stage (III-IV) oral tongue squamous cell carcinoma (OTSCC). Retrospective database review. National Cancer Database. A retrospective review of 3262 OTSCC cases in young patients between 2005 and 2014 was performed by using data from the National Cancer Database. Factors affecting 2-year survival in patients with early- and late-stage disease were evaluated via univariate and multivariate analyses. Overall, 1899 patients with early-stage OTSCC and 1363 with late-stage OTSCC were analyzed. In multivariate analysis of early-stage OTSCC, high tumor grade (hazard ratio, 2.08 [95% CI, 1.45-2.99]), local metastasis (2.85 [1.37-5.95]), and tumor size (1.04 [1.02-1.07]) were predictors of mortality. In late-stage OTSCC, African American race (2.79 [1.40-5.56]), positive surgical margins (1.77 [1.07-2.93]), local metastasis (2.20 [1.03-4.72]), distant metastasis (11.66 [2.10-64.73]), depth of invasion (1.03 [1.01-1.05]), and tumor size (1.01 [1.003-1.01]) were predictors of mortality. Subset analysis of clinical N0-stage tumors revealed that treatment with surgery alone was associated with improved survival (P < .001). Positive lymph nodes, high tumor grade, and larger tumor size were associated with increased mortality risk in early- and late-stage young OTSCC. More aggressive up-front treatment, including extirpative surgery and elective neck dissection, may be associated with improved outcomes and should be considered in early-stage cases with high-risk features.

Significance of Pattern of Invasion in Tongue Squamous Cell Carcinoma-A Retrospective Study from a Regional Cancer Center of North-East India.

Introduction Many multiparametric models and scoring systems had been proposed in oral tongue squamous cell carcinoma (OTSCC) to predict the survival and recurrence, out of which pattern of invasion (POI) is gaining focus recently. Objective We conducted a retrospective study with the aim to see the prognostic significance of the POI and other parameters such as depth of invasion, perineural invasion (PNI), and lymph node status in OTSCC. Materials and Methods The slides of already diagnosed OTSCC cases were prepared from January 2015 to December 2017 records and studied by two pathologists for different patterns using Brandwein-Gensler scoring system. The different clinicopathologic parameters were compared with different POI. Statistical analysis was performed to present cumulative survival outcomes and for comparison. Results Most of our patients were > 40 years of age with male preponderance. Tumor differentiation pattern was assessed using Broders' system of grading that showed 85% of tumors were well, 12.5% tumors were moderately differentiated, and 2.5% tumors were poorly differentiated. The worst POI was predominantly pattern III (50%) followed by pattern II (32.5%) and pattern IV (13.8%). Most patients were in stage II (33.8%) followed by stage III (32.5%), stage IV (26.3%), and stage I (7.5%). There was an inverse relationship between POI with tumor stage and recurrence. A strong statistically significant association was found between POI with perineural infiltration and lymph node metastasis. Conclusion We concluded from our study that worst POI is significantly associated with number of lymph nodes metastasis and perineural infiltration and hence can be used as an independent prognostic factor.

Immunoexpression of REGγ and apoptosis-related proteins in oral tongue squamous cell carcinoma

The aim of this study was to investigate the immunohistochemical expression of REGγ, p53, MDM-2, Bcl-2, and Bax in oral tongue squamous cell carcinoma (OTSCC), and to correlate the findings with clinicopathological parameters. Fifty-eight OTSCC cases were selected for the study. The percentages of nuclear (REGγ, p53, and MDM-2) and cytoplasmic (Bcl-2 and Bax) staining in epithelial cells were determined and correlated with clinicopathological parameters (regional lymph node metastasis, clinical stage, clinical outcome, and histopathological grade of malignancy). Expression of REGγ was observed in all cases studied. Significantly lower percentages were observed in tumours with lymph node metastasis (P = 0.036) and in high-grade tumours (P = 0.013). No significant differences in p53, MDM-2, or Bax expression were observed according to the clinicopathological parameters. Lower percentages of Bcl-2 staining were found in high-grade OTSCC (P = 0.040) and in cases of disease-related death (P = 0.032). The expression of REGγ showed a weak positive correlation with the expression of MDM-2 (P = 0.001) and Bcl-2 (P = 0.014). The results of this study suggest that lower expression of REGγ may contribute to the progression of OTSCC. The role of REGγ in the development of OTSCC does not appear to be primarily related to the modulation of apoptosis in neoplastic cells.

Polymorphisms of matrix metalloproteinase-7 and -9 are associated with oral tongue squamous cell carcinoma.

Matrix degradation is an important event in the progression, invasion and metastasis of malignant head and neck lesions. Imbalances, mutations and polymorphisms of MMPs and their inhibitors are observed in several cancer subtypes. The aim of this study was to evaluate the association of the MMP-7 gene promoter (181 A/G) and MMP-9 (-1562 C/T) polymorphisms in oral tongue squamous cell carcinoma (OTSCC). MMP-7 (rs11568818) and MMP-9 (rs3918242) single-nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 71 cases of OTSCC. Normal tissue specimens were obtained from 60 healthy volunteers to serve as the control. The MMP-7 G allele and MMP-9 T allele were more frequent in the OTSCC group than the control group, but only when these two SNPs were taken together was a significant association found with the nodal metastasis of OTSCC (p < 0.001). Based on our results, SNPs in the promoter region of MMP-7 and MMP-9 appear to be associated with greater risk of developing OTSCC, and with a higher propensity to form metastatic tumors. In this respect, molecular studies investigating polymorphisms may be useful in predicting tumor behavior.

CLINICOPATHOLOGICAL AND PROGNOSTIC SIGNIFICANCE OF PAI-1 EXPRESSION IN ORAL TONGUE SQUAMOUS CELL CARCINOMA

Objective: The purpose of this study was to evaluate the expression of plasminogen activator inhibitor type-1 (PAI-1) and its association with clinicopathological parameters and survival rates of oral tongue squamous cell carcinoma (OTSCC). Study Design: Sixty cases of OTSCC were selected for morphologic and immunohistochemical study. Each case was histopathologically graded according to Almangush et al. (2015). Cytoplasmic and membrane immunoexpression of PAI-1 were semiquantitatively analyzed at the deep invasive front. Pearson χ2 and Fisher exact test were performed to investigate the relationship between immunohistochemical findings and clinicopathological characteristics. Survival analyses were performed using the Kaplan-Meier method and log-rank test. Results: PAI-1 was highly expressed by neoplastic and stromal cells. No statistically significant associations were found between cytoplasmic immunopositivity for PAI-1 and clinical stage, nodal metastasis, local recurrence, disease outcome, or histopathological grade of malignancy (P> .05). Membrane immunopositivity for PAI-1 was significantly associated with tumor budding and histopathological risk-assessment score (P< .05). Cytoplasmic and membrane expression of PAI-1 were not associated with disease-specific or disease-free survival (P> .05). Conclusion: Our findings suggest that PAI-1 partly influences the biological behavior of OTSCC. However, the immunoexpression of this protein may not be useful to predict survival of the studied lesion. Objective: The purpose of this study was to evaluate the expression of plasminogen activator inhibitor type-1 (PAI-1) and its association with clinicopathological parameters and survival rates of oral tongue squamous cell carcinoma (OTSCC). Study Design: Sixty cases of OTSCC were selected for morphologic and immunohistochemical study. Each case was histopathologically graded according to Almangush et al. (2015). Cytoplasmic and membrane immunoexpression of PAI-1 were semiquantitatively analyzed at the deep invasive front. Pearson χ2 and Fisher exact test were performed to investigate the relationship between immunohistochemical findings and clinicopathological characteristics. Survival analyses were performed using the Kaplan-Meier method and log-rank test. Results: PAI-1 was highly expressed by neoplastic and stromal cells. No statistically significant associations were found between cytoplasmic immunopositivity for PAI-1 and clinical stage, nodal metastasis, local recurrence, disease outcome, or histopathological grade of malignancy (P> .05). Membrane immunopositivity for PAI-1 was significantly associated with tumor budding and histopathological risk-assessment score (P< .05). Cytoplasmic and membrane expression of PAI-1 were not associated with disease-specific or disease-free survival (P> .05). Conclusion: Our findings suggest that PAI-1 partly influences the biological behavior of OTSCC. However, the immunoexpression of this protein may not be useful to predict survival of the studied lesion.

Appraising Oncogenic Long Noncoding RNAs as Novel Biomarkers for Oral Tongue Squamous Cell Carcinoma: a Meta-Analysis

Long noncoding RNAs (lncRNAs) are rapidly emerging as a novel class of transcripts associated with tumorigenesis and prognosis of oral tongue squamous cell carcinoma (OTSCC). The goal of this study was to perform a meta-analysis of the prognostic utility of tumorigenic lncRNAs as novel biomarkers of OTSCC and their associations with the clinicopathological features of OTSCC. Online databases were searched for eligible studies. The hazard ratio (HR) with 95% CI was used to predict survival. The individual p-values for clinicopathological features were respectively combined using Fisher's method. A total of 11 studies covering 1,138 OTSCC cases were included for quantitative data synthesis. Oncogenic lncRNA expression signature was closely related to shortened overall survival (OS) of patients with OTSCC (HR = 1.85, 95% CI: 1.45 - 2.37, p = 0.001; I2 = 64.9%; p = 0.002). Stratified analysis based on clinicopathological features showed that abnormally expressed lncRNAs were significantly associated with clinical stage (p = 0.000), node metastasis (p = 0.025), T stage (p = 0.000), and nodal stage (p = 0.000). Collectively, oncogenic lncRNAs were implicated in the development and progression of OTSCC, and may serve as novel biomarkers for predicting the prognosis of OTSCC patients.

Cell cycle markers and apoptotic proteins in oral tongue squamous cell carcinoma in young and elderly patients.

The immunoexpression of p16, p53, and Bax in oral tongue squamous cell carcinoma (OTSCC) in young and elderly patients is assessed based on clinical and morphological parameters. The sample consists of 60 OTSCC cases: 30 in young (age ≤ 45 years) and 30 in elderly (age ≥ 60 years) patients. Clinical (tumor size, regional node metastasis, distant metastasis, and clinical stage) and morphological (histological grade of malignancy) parameters were evaluated. Immunohistochemical quantitative analysis was performed using anti-p16, anti-p53, and anti-Bax antibodies. None of the evaluated proteins exhibited statistically significant differences between young and elderly patients (p>0.05). There was a significant association of p16 immunoexpression with clinical parameters in elderly patients. There were no associations of p53 and Bax with any of the clinico-morphological parameters. Correlations between p16 and Bax and between p53 and Bax immunoexpression were observed in young patients (r = 0.363; p = 0.048) and in elderly patients (r = 0.433; p = 0.017), respectively. In conclusion, the assessed proteins could not be used to determine differences in the biological behavior of OTSCC between young and elderly patients. Therefore, all proteins activated the pro-apoptotic pathway of OTSCC in both groups.

Oral tongue squamous cell carcinoma survival as stratified by age and sex: A surveillance, epidemiology, and end results analysis

To utilize the Surveillance, Epidemiology, and End Results (SEER) database to elucidate differences in predictors of survival in oral tongue squamous cell carcinoma (OTSCC) as stratified by age and sex. Retrospective, population-based database analysis. The SEER registry was utilized to calculate survival trends for patients with OTSCC between 1973 and 2012. Patient data were then stratified by age (≤40 years vs. >40 years) and sex, then analyzed with respect to race, stage, grade, and treatment modalities. Overall survival (OS) and disease-specific survival (DSS) were calculated and compared. There were 16,423 cases of OTSCC identified, with 526 and 706 young female and male patients, respectively. Young female patients had improved OS and DSS as compared to young male patients (75% vs. 67% at 5 years), which is better than older patients (P < .001). Younger patients were more likely to receive surgery (P < .001) and combination surgery and radiation (P < .001) as compared to older patients. On multivariate analysis, tumor stage was uniformly associated with worse OS and DSS (P < .05), with surgery predicting improved OS and DSS in all groups except young females (P < .05). Higher tumor grade predicted worse OS and DSS in older patients, but not younger patients (P < .05). OTSCC appears to present with relatively heterogeneous characteristics across different age groups and sexes. Despite the rising incidence of OTSCC in young individuals, our study demonstrates that young patients have improved survival rates compared to older patients. NA Laryngoscope, 129:2076-2081, 2019.

Prognostic impact of tumour-stroma ratio in early-stage oral tongue cancers.

Oral tongue squamous cell carcinoma (OTSCC) has a relatively poor outcome, and there is a need to identify better prognostic factors. Recently, tumour-stroma ratio (TSR) has been associated with prognosis in several cancers. The aim of this multi-institutional study was to evaluate the prognostic value of TSR from original haematoxylin and eosin (HE)-stained tumour-resection slides in a series of early-stage (cT1-2N0) OTSCC patients. A TSR cutoff value of 50% was used to divide the patients into stroma-rich (≥50%) and stroma-poor (<50%) groups. The relationships between TSR and clinicopathological characteristics of 311 early-stage OTSCC cases were analysed. The prognostic value of TSR in OTSCC was calculated separately and in combination with a previously published cancer cell budding and depth of invasion (BD) prognostic model. A total of 89 cases (28.6%) belonged to the stroma-rich group. In a multivariate analysis, the stroma-rich group had worse disease-free survival, with a hazard ratio (HR) of 1.81 [95% confidence interval (CI) 1.17-2.79, P = 0.008], and higher cancer-related mortality (HR 1.71, 95% CI 1.02-2.86, P = 0.03). The combination of the highest-risk parameter scores of TSR and the BD model showed significant correlations with recurrence rate (HR 3.42, 95% CI 1.71-6.82, P = 0.004) and cancer-related mortality (HR 11.63, 95% CI 3.83-35.31, P < 0.001). We conclude that TSR is a simple histopathological feature that is useful for prognostication of early-stage OTSCC, and suggest that TSR analyses in association with BD score could be included in routine clinical pathology reports for HE-stained slides.

ANALYSIS OF THE ASSOCIATION OF DNA NUCLEOTIDE EXCISION REPAIR PROTEINS WITH PROGNOSTIC PARAMETERS IN ORAL TONGUE SQUAMOUS

Genomic instability comprises one of the main events of carcinogenesis and tumor progression. The objective of this study was to analyze the immunoreactivity of DNA nucleotide excision repair proteins, THIIF and XPF, in oral tongue squamous cell carcinoma (OTSCC) and investigate possible associations with clinical parameters and outcome. Fifty cases of OTSCC were stained by immunohistochemistry and the expression of THIIF and XPF proteins were measured by semi-quantitative analysis. Clinical variables of interest were collected from patients' charts and statistical tests were performed (Chi-square and Fisher's exact tests, significance of 5%) to investigate associations between these data and proteins immunoexpression. High expression of the studied proteins in parenchymal cells was observed; however, significant association of proteins immunoexpression with TNM staging, locoregional recurrence, and death was not identified. The results of this experiment suggest that TFIIH and XPF proteins participate in the tumorigenesis process; however, their immunoexpression cannot be used as an independent prognostic indicator for OTSCC.

Three-Dimensional Reconstruction of Oral Tongue Squamous Cell Carcinoma at Invasion Front

We conducted three-dimensional (3D) reconstruction of oral tongue squamous cell carcinoma (OTSCC) using serial histological sections to visualize the architecture of invasive tumors. Fourteen OTSCC cases were collected from archival paraffin-embedded specimens. Based on a pathodiagnostic survey of whole cancer lesions, a core tissue specimen (3 mm in diameter) was dissected out from the deep invasion front using a paraffin tissue microarray. Serial sections (4 μm thick) were double immunostained with pan-cytokeratin and Ki67 antibodies and digitized images were acquired using virtual microscopy. For 3D reconstruction, image registration and RGB color segmentation were automated using ImageJ software to avoid operator-dependent subjective errors. Based on the 3D tumor architecture, we classified the mode of invasion into four types: pushing and bulky architecture; trabecular architecture; diffuse spreading; and special forms. Direct visualization and quantitative assessment of the parenchymal-stromal border provide a new dimension in our understanding of OTSCC architecture. These 3D morphometric analyses also ascertained that cell invasion (individually and collectively) occurs at the deep invasive front of the OTSCC. These results demonstrate the advantages of histology-based 3D reconstruction for evaluating tumor architecture and its potential for a wide range of applications.

Nerve Growth Factor and Tyrosine Kinase A Receptor in Oral Squamous Cell Carcinoma: Is There an Association With Perineural Invasion?

Perineural invasion (PNI) in oral squamous cell carcinoma (SCC) is recognized as a significant predictor of outcome. PNI is associated with locoregional recurrence and decreased survival of patients with head and neck SCC. Nerve growth factor (NGF) has been shown to be involved in PNI in several malignancies, including breast, prostate, and pancreatic cancers. We investigated the hypothesis that NGF and its high-affinity receptor tyrosine kinase A (TrkA) are highly expressed in cases of oral SCC that have histologic evidence of PNI. We performed immunohistochemistry on archived oral tongue SCC specimens from the established oral and general pathology databases at the University of California, San Francisco. The following groups were evaluated: 1) 21 T1/T2 oral tongue SCC cases with PNI and 2) 21 T1/T2 oral tongue SCC cases without histologic evidence of PNI. Strong homogeneous cytoplasmic staining for NGF and TrkA was detected in the malignant cells in the PNI-positive group of tumors. In group II (PNI negative) NGF and TrkA were detected in the stroma cells or were very weakly expressed by the malignant cells. We were able to show the presence of NGF and TrkA in the cytoplasm of malignant squamous cells in tumors with histologic evidence of PNI. Immunostaining for NGF (P = .0001) and TrkA (P = .039) was significantly higher in the PNI-positive oral SCC group than in the PNI-negative oral SCC group. This study shows that oral SCC with evidence of PNI shows increased expression of NGF and TrkA and suggests that NGF and TrkA are involved with the mechanism leading to PNI. Further investigations are warranted to determine the potential for use of NGF and TrkA as candidate biomarkers to predict progression and outcome.