Primary Tongue Squamous Cell Carcinoma Research Articles

Prognostic factors in surgically treated tongue squamous cell carcinoma in stage T1-2N0-1M0: A retrospective analysis.

The study aimed to retrospectively identify the prognostic factors of surgically treated primary tongue squamous cell carcinoma (TSCC) cases and assess the benefits of surgical neck lymph node dissection (LND) in early-stage cancer. Patients with primary TSCC with pT1-2N0-1M0 stage without distant metastasis who were treated with surgery during 2014-2016 at Xiangya Hospital, Central South University were included. Univariate and multivariate Cox models were constructed to explore prognostic factors of overall survival (OS), disease-free survival (DFS), and local recurrence-free survival (LRFS). Sub-group analysis was used to assess the effect of adjuvant therapy and the prognostic value of LND for the early-stage patients. In total, 440 patients met the inclusion criteria. During the follow-up period, the 5-year OS, DFS, were 84.4% and 70.0%, respectively. Univariate analysis showed that TNM stage, lymphovascular invasion (LVI), and/or perineural invasion (PNI), pathological differentiation, etc. were significant predictors of OS and DFS. Multivariate analysis showed that TNM stage and the degree of pathological differentiation were independent prognostic factors for all outcomes. Besides, the number of cervical LND could independently predict both DFS and LRFS while LVI/PNI were associated with DFS. And high-quality neck LND (≥30) significantly improved DFS and LRFS for patients of pT1cN0M0 or stage I as compared to those without LND. TNM stage and pathological differentiation were crucial prognostic factors for postoperative patients with TSCC. Notably, high-quality cervical LND was beneficial for the improvement of DFS and LRFS for patients of pT1cN0M0 or stage I.

Clinical study on the pattern of lower-level lymphatic metastasis in primary tongue squamous cell carcinoma.

To study and analyze the clinical patterns of lower-level lymph node (Ⅳ and Ⅴ) metastasis in primary tongue squamous cell carcinoma, and establish a reference for the decision-making of the lower-level neck dissection in tongue squamous cell carcinoma. A total of 203 patients with primary tongue squamous cell carcinoma were recruited. These patients underwent simultaneous/secondary comprehensive neck (level Ⅰ-Ⅴ) dissection in Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine from January 2010 to December 2015. Their clinicopathological and follow-up data were obtained and analyzed to reveal the prognosis and risk factors of primary tongue squamous cell carcinoma with lower-level lymph node metastasis. Among the 203 patients, the metastasis rates of levels Ⅳ and Ⅴ are 14.78% and 4.93%, respectively. Level Ⅳ metastasis is more prevalent in males than females (P=0.04); non-smokers are more likely to have level Ⅴ metastasis than smokers (P=0.046). Lymph node status in levels Ⅲ and Ⅳ are significantly associated with the risk of metastasis in level Ⅴ (P=0.001). Patients with extracapsular invasion in level Ⅲ have a significantly increased risk of metastasis in levels Ⅳ (P=0.014) and Ⅴ (P=0.026). The 5-year survival rate of patients with lower lymph node (Ⅳ/Ⅴ) metastasis is only 14.70%, which is an independent poor prognostic factor for patients with primary tongue squamous cell carcinoma (P<0.000 1). Most primary tongue squamous cell carcinoma metastases occur in levels Ⅰ-Ⅲ. However, the rate of lower-level lymph node metastasis is rather low. For the cN0 and cN+ patients with levels Ⅰ-Ⅱ lymph node metastases without extracapsular invasion, the strategy for level Ⅴ management may be observation rather than dissection.

Feasibility of dpFAMM flap in tongue reconstruction after facial vessel ligation and radiotherapy\u2014case presentation

BackgroundSalvage surgery with reconstruction of the second and next primary tongue cancer remains difficult, especially after earlier neck dissection and radiotherapy. In the current report, we describe the feasibility of the extended, double-pedicled facial artery musculomucosal (dpFAMM) flap in the reconstruction of the patient with second primary tongue squamous cell carcinoma, after facial vessel ligation and radiotherapy.Case presentationAn 81-year-old female patient was operated on due to tongue squamous cell carcinoma (SCC) on the left side T3N1M0 in 2019. Bilateral selective neck dissection with tongue reconstruction was performed by island FAMM flap. The patient also suffered from synchronous mucinous breast carcinoma treated with tamoxifen. The second primary SCC of the tongue on the opposite (right) side was detected in 2020. The patient did not agree to surgical treatment; therefore, radiotherapy was performed. The local recurrence of the tongue cancer of the right side was treated surgically in 2021. Salvage surgery comprised hemiglossectomy and dpFAMM flap reconstruction with uneventful postoperative follow-up.ConclusionsThis case presentation proved that dpFAMM flap can be used in salvage surgery and reconstruction even in patients after ligation of facial vessels, irradiation, and in the course of hormone therapy. The flap is easy to handle, has good vascularity, and comprises a predictable method of reconstruction, especially for patients with severe comorbidities.

Clinicopathological and Prognostic Analysis of PD-L1 and PD-L2 Expression in Surgically Resected Primary Tongue Squamous Cell Carcinoma.

The expression of tumor-associated programmed death-ligand 1 (PD-L1) predicts clinical responses to PD-1-directed immunotherapy. The expression levels of PD-L2, another PD-1 ligand, and its relationship with responses to PD-1-targeting therapy in oral squamous cell carcinoma (OSCC) remain unclear. Furthermore, the clinicopathological characteristics and prognostic effects of the expression of PD-L1 and PD-L2 in OSCC have not yet been elucidated. The expression of PD-L1 and PD-L2 was immunohistochemically examined in 98 tongue carcinomas. Furthermore, the expression levels of PD-L1 and PD-L2 in OSCC cell lines and their relationships with those of MMP2 and MMP9 were assessed. The expression levels of PD-L1 and PD-L2 correlated with those of MMP2 and MMP9. The expression of PD-L1 and/or PD-L2 was detected in OSCC cells, and their levels correlated with those of MMP9. The prognosis of patients with PD-L1- and PD-L2-positive tumors was significantly worse. PD-L1 and PD-L2 status is potentially a novel predictor of the prognosis of OSCC and provides a rationale for the development of novel immunotherapies.

Salvage Surgery for Recurrent Tongue Cancer With Contralateral Neck Metastasis

Treatment recommendations have been widely reported for primary tongue squamous cell carcinoma (TSCC) with contralateral neck metastases (CNMs), but little is known concerning recurrent TSCCs with CNMs, especially in patients who have undergone ipsilateral neck dissection. The aim of this study was to estimate overall survival (OS) and to identify prognostic factors associated with OS in patients treated for recurrent TSCCs. We performed a retrospective cohort study of patients who underwent salvage surgery (SS) for recurrent TSCC in our institution between January 2010 and December 2014. Before SS, all patients had been surgically treated for primary TSCC with ipsilateral neck dissection. The primary outcome variable was OS, and the patients were grouped by the primary predictor variable of CNM status for comparison. Other heterogeneous variables of interest included demographics, medical histories, clinicopathologic characteristics, surgical data, and adjuvant treatment modalities. In addition, the midline involvement and anatomic subsites of local recurrences were evaluated. Univariate log-rank and Cox regression tests were used for statistical analyses. The study sample included 177 subjects with a mean age of 55.4years, and 44.6% were males. The median OS was 18months. Within the entire cohort, the incidence of CNM was 23.7% (n=42), with an inclination (n=30) for contralateral level I or II. Factors associated with improved survival included CNM (hazard ratio [HR], 2.108; 95% confidence interval [95% CI], 1.341 to 3.315; P=.001), disease-free interval (HR, 0.601; 95% CI, 0.387 to 0.934; P=.023), and local recurrence subsite score (HR, 3.276; 95% CI, 0.924 to 11.623; P=.001). Patients with both recurrent TSCCs and CNMs had a dismal prognosis (OS rate, 16.2%) compared with those without CNMs (OS rate, 52.7%). SS for TSCC patients with collateral failures should be used cautiously because of the very unfavorable outcomes.

High detection sensitivity and reliable morphological correlation of PET with a silicon photomultiplier for primary tongue squamous cell carcinoma.

A positron emission tomography (PET) scanner using a silicon photomultiplier (SiPM PET) in place of a photomultiplier tube significantly improves the spatial and time resolution. It may also improve the evaluation of smaller lesions compared to conventional (non-SiPM) PET scanners. We compared the maximum standardized uptake value (SUVmax), detection sensitivity, and morphological correlation using magnetic resonance imaging (MRI) for primary tongue squamous cell carcinoma between the SiPM PET and non-SiPM PET scanner. We retrospectively reviewed the F-18 fluorodeoxyglucose (FDG) PET/CT features of tongue squamous cell carcinomas in consecutive, newly diagnosed, and pathologically verified patients. Twenty-five of 46 patients were scanned using SiPM PET scanner and the remaining 21 patients were scanned with a non-SiPM PET scanner. We compared the SUVmax and visual evaluation of primary tumor detectability, and the correlation between the PET-based and MRI-based tumor size (long axis, thickness, and volume). Differences in SUVmax and detection sensitivity for the primary tumor were analyzed using Welch's t test and Fisher's exact test, respectively. Correlations among the PET-based, MRI-based tumor size, and SUVmax were assessed using Spearman's rank correlation coefficient. SUVmax of both T1/T2 and T3/T4 primary tumors were significantly higher for the SiPM PET (T1/T2 mean SUVmax: 6.6 ± 4.3, T3/T4 mean SUVmax: 18.2 ± 9.8) than that for the non-SiPM PET (T1/T2 mean SUVmax: 3.4 ± 1.4, T3/T4 mean SUVmax: 10.2 ± 4.9) (P < 0.05). While all cases of T3/T4 primary tumors were detected by both PET scanners, the detection sensitivity for T1/T2 primary tumors was significantly higher for the SiPM PET (80%) than that for the non-SiPM PET (36.4%) (P < 0.05). MRI-based tumor size correlated significantly with SiPM PET-based tumor long axis (ρ = 0.74) and volume (ρ = 0.91), but not with the non-SiPM PET-based tumor long axis and volume in T1/T2 primary lesions. Correlation between MRI-based tumor size and SUVmax was significant in both PET scanners; however, no significant difference was observed between the two scanners. The SiPM PET provides better detection sensitivity and a reliable morphological correlation for the T1/T2 primary tongue tumors than the non-SiPM PET due to its high performance.

Comparison of Clinical Results and Quality-of-Life in Tongue Cancer Patients Undergoing Submental Island Flap and Radial Forearm Free Flap Reconstruction

Our goal was to compare the clinical results and quality-of-life (QoL) in tongue cancer patients undergoing submental island pedicled (SIP) flap and radial forearm free (RFF) flap reconstruction. Patients undergoing SIP or RFF flap reconstruction for primary tongue squamous cell carcinoma were prospectively enrolled and were asked to complete the University of Washington Quality-of-Life (UW-QOL) questionnaire, version 4, at 12months after the operation. The study's main interest was QoL as well as locoregional recurrence control. A total of 190 patients were enrolled for analysis, and the SIP and RFF groups showed significant differences in patient age, American Society of Anesthesiologists classification, and hospital cost. In the survival analysis, locoregional recurrence occurred in 35 patients in the SIP group and 48 patients in the RFF group; the difference was not significant (P=.440). In the QoL analysis, compared with patients in the SIP group, those in the RFF group had higher scores in the domains of activity and recreation. No significant differences were found with respect to the other domains. The SIP flap and RFF flap have comparable survival control in tongue squamous cell carcinoma patients. The RFF flap might lead to better QoL, but the SIP flap imposes fewer limitations on patients' health status and is associated with lower hospital cost.

CBX3/HP1γ is upregulated in tongue squamous cell carcinoma and is associated with an unfavorable prognosis.

Increased expression of CBX3/HP1γ, a core component of heterochromatin protein 1, has recently proved to be involved in human tumorigenesis and patient prognosis. The present study aimed to investigate the expression of CBX3/HP1γ and its clinicopathological significance in primary tongue squamous cell carcinoma (TSCC). Gene expression profiles of CBX3/HP1γ in TSCC from Oncomine database were analyzed. The expression of CBX3/HP1γ at protein level was measured using immunohistochemistry (IHC). The potential associations between CBX3/HP1γ expression and multiple clinicopathological parameters were estimated using the Chi square test. In addition, the effect of CBX3/HP1γ expression on patients' survival was further assessed by Kaplan-Meier and Cox regression analyses. The agreement of elevated CBX3/HP1γ expression was indicated in four datasets on the Oncomine database. Aberrant overexpression of CBX3/HP1γ was identified in TSCC tissues compared with cancer-adjacent normal tissue, which was significantly associated with cervical nodes metastasis (P=0.010) and clinical stage (P=0.025). Furthermore, patients with high CBX3/HP1γ expression exhibited a reduced survival compared with those with low expression (Log-rank test, P=0.004). Univariate and multivariate Cox regression analysis suggested that the expression status of CBX3/HP1γ could be regarded as an independent prognostic factor for TSCC patients (HR=2.461; 95% CI=1.128–5.370; P=0.024). The present study indicated that aberrant overexpression of Cbx3/HP1γ was associated with cervical nodes metastasis and unfavorable survival in TSCC. These findings suggest that CBX3/HP1γ may serve an important role in tongue tumorigenesis and may be a valuable candidate diagnostic and prognostic marker for TSCC patients.

Differences in Clinicopathological Characteristics and Prognosis Between Primary and Postirradiation Tongue Squamous Cell Carcinoma

Many cases of postirradiation oral carcinoma have been reported, but its prognosis and optimal treatment modalities are not clear. Thus, the clinicopathologic characteristics and prognosis between postirradiation tongue squamous cell carcinoma (PTSCC) and primary tongue squamous cell carcinoma (TSCC) were compared. A retrospective cohort study was conducted to assess patients with PTSCC or TSCC. The primary predictor variable was tumor type. The primary outcome variable was prognosis, and the additional outcome variables were clinicopathologic characteristics. Survival analysis was performed, and Kaplan-Meier analysis was conducted to compare the effects of clinicopathologic factors on survival using SPSS 18.0. Moreover, the Cox model was applied in multivariate analysis. The sample was composed of 449 patients with PTSCC (n=68; 47 men and 21 women; age range, 31 to 72yr) and TSCC (n=381; 247 men and 134 women; age range, 20 to 86yr). Patients with PTSCC were found to have a substantially poorer prognosis and several specific clinicopathologic characteristics compared with patients with TSCC. Patients with PTSCC had several unique biological tumor characteristics and a poorer prognosis than patients with TSCC. Thus, different surgical strategies should be used to treat patients with PTSCC.

Overexpression of suppressor of zest 12 is associated with cervical node metastasis and unfavorable prognosis in tongue squamous cell carcinoma

ObjectiveIncreased expression of suppressor of zest 12 (SUZ12), a core component of the polycomb repressive complex 2, contributes to human tumorigenesis and associates with patient prognosis. In the present study, we sought to investigate the expression of SUZ12 and its clinicopathological significance in primary tongue squamous cell carcinoma (TSCC).MethodsThe expression of SUZ12 protein was determined by immunohistochemistry in clinical samples from a retrospective cohort of 72 patients with primary TSCC who were treated at our institution from Jan. 2007 to Dec. 2013. The potential associations between SUZ12 abundance and multiple clinicopathological parameters were assessed by Chi square test. Moreover, the effect of SUZ12 expression on patients’ survival was further estimated by Kaplan–Meier and Cox regression analyses.ResultsOur immunohistochemical staining data revealed aberrant overexpression of SUZ12 in a large subset of TSCC as compared to normal tongue mucosa. Elevated SUZ12 was found to be significantly associated with cervical nodes metastasis (P = 0.0325) and reduced overall as well as disease-free survival (Log-rank test, P = 0.0225, 0.0179, respectively). Both univariate and multivariate Cox regression analysis identified the expression status of SUZ12 (low/high) as an important independent prognostic factor for patients’ survival.ConclusionsOur data reveal that aberrant SUZ12 overexpression is associated with cervical nodes metastasis and reduced survival in TSCC. These findings suggest that SUZ12 might play critical roles during tongue tumorigenesis and serve as a novel biomarker with diagnostic and prognostic significance.

Upregulated long non-coding RNA LINC00152 expression is associated with progression and poor prognosis of tongue squamous cell carcinoma.

Altered expression of long non-coding RNAs (lncRNAs) associated with human carcinogenesis and might be used as diagnosis and prognosis biomarkers. However, the expression of lncRNAs in tongue squamous cell carcinoma (TSCC) and their relevance on the diagnosis, progression and prognosis of TSCC have not been thoroughly elucidated. To discover novel TSCC-related lncRNAs, we analyzed the lncRNA expression patterns in two sets of previously published TSCC gene expression profile data (GSE30784 and GSE9844), and found that long intergenic non-coding RNA 152 (LINC00152) was significantly upregulated in TSCC samples. We then detected LINC00152 expression in two other cohorts of TSCC samples. Quantitative Real time PCR (qRT-PCR) results indicated that LINC00152 was highly expressed in 15 primary TSCC biopsies when compared with 14 adjacent non-tumor tongue squamous cell epithelium samples. The expression of LINC00152 was also measured in 182 paraffin-embedded human TSCC tissues by in situ hybridization, increased expression of LINC00152 was significantly correlated with TSCC progression, such as T stage (p = 0.009), N stage (p = 0.036), TNM stage (p = 0.017), and associated with relapse (p < 0.001), and invasion (p < 0.001). Kaplan-Meier analysis demonstrated that increased LINC00152 expression contributed to both poor overall survival (p = 0.006) and disease-free survival (p = 0.007) of TSCC patients. These findings suggest that LINC00152 might serve as a potential biomarker for early detection and prognosis prediction of TSCC.

High expression of podoplanin in squamous cell carcinoma of the tongue occurs predominantly in patients ≤40 years but does not correlate with tumour spread.

More than 30% of patients with squamous cell carcinoma (SCC) of the mobile tongue have clinically undetectable lymph node metastasis. Tumour cells can spread as single cells or collectively. A protein known to play a role in both processes is podoplanin, which is expressed in endothelial cells not only in lymph vessels but also in some aggressive tumours with high invasive and metastatic potential. Here we studied samples from 129 patients with primary SCC of the tongue for expression of podoplanin using immunohistochemistry. mRNA levels were analysed in another 27 cases of tongue SCC with adjacent clinically tumour‐free tongue tissue and 14 tongue samples from healthy donors. Higher levels of podoplanin were seen in tumours compared to both normal tongue and clinically normal tongue in the tumour vicinity. No association was found between levels of podoplanin, presence of lymph node metastases or other clinical factors. Patients aged 40 or less were more likely to express high levels of podoplanin protein compared to older patients (p = 0.027). We conclude that levels of podoplanin in primary tongue SCCs are not associated with lymph node metastases. However, tongue SCCs arising in young patients (≤40 years of age) are more likely to express high levels of podoplanin than tongue SCCs that arise in the more elderly. The data suggest that podoplanin has a distinctive role in young patients, who are known to have a poor prognosis: these patients may, therefore, benefit from podoplanin inhibitory therapies.

Abstract 4811: Pro-oncogenic role of NOTCH1 in early tongue squamous cell carcinoma

Abstract Notch pathway play a context-dependent tumor-suppressive or pro-oncogenic role in solid tumors and hematological malignancies. In head and neck cancer, inactivating mutations in NOTCH1 are associated with poor prognosis. Here we perform meta-analysis of DNA copy number and gene expression profiling of NOTCH signaling pathway genes in 35 paired primary T1 and T2 stage tongue tumors, comprising of Notch ligands, receptors and target genes. We find 32% of primary tongue squamous cell carcinoma (TSCC) tumors amplify NOTCH signaling pathway components; and over express activated NOTCH1based on immuno-histochemical staining in an additional series of 50 surgically resected paired TSCC tumors. Interestingly, these alterations: amplification at Notch ligand DLL3 (χ2 = 7.575, P = 0.023); over expression of Notch pathway target gene HEY2 transcript (χ2 = 9.885, P = 0.007); and expression of activated NOTCH1 (χ2 = 7.575, P = 0.023) positively correlate with N+ve and non- smoking status of patients. In a parallel effort, we characterized four HNSCC cell lines– NT8E, OT9, AW13516, and AW8507– established from Indian patients using whole exome, whole transcriptome sequencing and SNP array assays. Significant amplification and over expression of NOTCH signaling pathway components were observed in AW13516 and NT8E cells. Inhibition of NOTCH activation by gamma secretase inhibitor or shRNA mediated knockdown of NOTCH1 could inhibit transformation, survival, migration and invasion of NT8E cells. Taken together, we present that activation of Notch signaling pathway in a subset of TSCC patients is associated with nodal positivity and non-smoking status among early tongue cancer patients. Citation Format: Pawan Upadhyay, Jyotirmoi Aich, Vidyalakshmi Sethunath, Prachi Dani, Sadhana Kannan, Pratik Chandrani, Kavitha Sonawane, Beamon Agarwal, Shubhada Kane, Sudhir Nair, Amit Dutt. Pro-oncogenic role of NOTCH1 in early tongue squamous cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4811. doi:10.1158/1538-7445.AM2015-4811

Bmi1 drives stem-like properties and is associated with migration, invasion, and poor prognosis in tongue squamous cell carcinoma.

Bmi1 (B-cell-specific Moloney murine leukemia virus insertion site 1) had been found to involve in self -renewal of stem cells and tumorigenesis in various malignancies. The purpose of this study is to evaluate the role of Bmi1 in the development of tongue squamous cell carcinoma (TSCC) and its functional effect on the migration and invasion of TSCC. Initially, immunohistochemistry revealed that Bmi1 overexpression was a common event in premalignant dysplasia, primary TSCC, and lymph node metastases and was associated with a poor prognosis. A significant correlation between Bmi1 and SOD2 (manganese superoxide dismutase) expression was observed. Side population (SP) cells were used as cancer stem-like cells and further assessed by sphere and colony formation assays, and the expression of stem cell markers. TSCC cells with higher migration and invasion ability (UM1 cell lines) showed a higher proportion of SP cells and Bmi1 expression than TSCC cells with lower migration and invasion ability (UM2 cell lines). Knockdown of Bmi1 in UM1 or SP cells inhibited migration and invasion and decreased the sphere and colony formation, and the expression of stem cell markers and SOD2. Direct binding of C-myc to the Bmi1 promoter was demonstrated by chromatin immunoprecipitation and luciferase assays. Moreover, C-myc knockdown in SP cells inhibited their migration and invasion and decreased the expression of Bmi1 and SOD2. Our results indicate that the deregulation of Bmi1 expression is a frequent event during the progression of TSCC and may have a prognostic value for patients with this disease. The Bmi1-mediated migration and invasion of TSCC is related to cancer stem-like cells and involves the C-myc-Bmi1-SOD2 pathway.

Neutrophils Infiltration in the Tongue Squamous Cell Carcinoma and Its Correlation with CEACAM1 Expression on Tumor Cells

ObjectiveThe present study aimed to explore the clinical significance of neutrophils infiltration and carcinoembryonic antigen related cell adhesion molecule 1 (CEACAM1) expression in the tongue squamous cell carcinoma (TSCC), and to probe the possible relationship between them.Materials and MethodsTissue microarray and immunohistochemistry were used to detect neutrophils density and CEACAM1 expression in 74 cases of primary TSCC specimens and 17 cases of corresponding peritumoral tissues. The relationship of CEACAM1 expression and neutrophils density with clinicopathologic parameters and cancer-related survival of TSCC patients were evaluated. The correlation between CEACAM1 expression and neutrophils density was also evaluated. Real-time quantitative transcription polymerase chain reaction (qRT-PCR) was used to explore the possible molecular mechanisms between CEACAM1 expression and neutrophils infiltration.ResultsImmunohistochemistry evaluation revealed that there was more neutrophils infiltration in TSCC tissues than in peritumoral tissues. High neutrophil density was associated with LN metastasis (P = 0.01), higher clinical stage (P = 0.037) and tumor recurrence (P = 0.024). CEACAM1 overexpression was also associated with lymph node metastasis (P = 0.000) and higher clinical stage (P = 0.001). Survival analysis revealed that both neutrophils infiltration and CEACAM1 overexpression were associated with poorer cancer-related survival of TSCC patients (P<0.05), and neutrophils infiltration was an independent prognostic factor for TSCC (P<0.05). Furthermore, overexpression of CEACAM1 was correlated with more neutrophils infiltration in TSCC tissues (P<0.01). qRT-PCR results showed that CEACAM1-4L can upregulate the mRNA expression of IL-8 and CXCL-6, which were strong chemotactic factors of neutrophils.ConclusionOur results demonstrated that more neutrophils infiltration and overexpression of CEACAM1 were associated with poor clinical outcomes in TSCC tissues. Overexpression of CEACAM1 on tumor cells correlated with more neutrophils infiltration to some extent through upregulating mRNA expression of IL-8 and CXCL-6.

Mechanisms Underlying Cancer Progression Caused by Ezrin Overexpression in Tongue Squamous Cell Carcinoma

BackgroundEzrin is a member of the ezrin, radixin, and moesin family that provides a functional link between the plasma membrane and the cortical actin cytoskeleton. A correlation between ezrin overexpression and aggressive cancer behavior has been recently reported in various tumor types. However, its roles in the mechanisms underlying progression of tongue squamous cell carcinoma (SCC) are unclear.MethodWe used human tongue SCC and noncancerous tissue microarrays to immunohistochemically analyze the ezrin expression level and its relationship with proliferative activity. The human tongue SCC cell line HSC-3 was used to determine the effects of ezrin RNA interference (RNAi) on cancer cells during MTT; wound healing and invasion assays; immunofluorescence of the actin cytoskeleton; and western blotting of E-cadherin, N-cadherin, β-catenin, and the active and total RhoA/Rac1/cdc42.ResultsEzrin was overexpressed in 46.4% of the tumors examined in human tongue SCC tissue microarrays. Ezrin expression was correlated with the Ki-67 index. Ezrin depletion by RNAi in the HSC-3 cells significantly reduced cell proliferation, migration, and invasiveness and disturbed actin reorganization during podia formation. Its effects on RhoA/Rac1/cdc42 expression were not significant, whereas it enhanced E-cadherin and β-catenin expression and decreased N-cadherin expression.ConclusionsEzrin is often overexpressed in primary tongue SCCs and may have an important role in their growth, migration, and invasiveness possibly via its relationship with the E-cadherin/β-catenin complex and the cadherin switch. Thus, ezrin could be a therapeutic target in tongue SCC.

Aberrant expression of the ZDHHC14 gene in squamous cell carcinoma of the human tongue

Objective The aim of this study was to identify differentially expressed gene(s) among lymph node-positive (pN+) cases and lymph node-negative (pN−) cases of tongue squamous cell carcinoma (TSCC). Patients and methods We examined genetic aberrations and gene expression profiles in 20 cases of primary TSCCs, paired normal oral tissues, six TSCC-derived cell lines, and normal oral keratinocytes (NOKs). Whole genome profiling using the Affymetrix 10K SNP Mapping Array was performed on three pN+ cases and two pN− cases of TSCCs and the results were compared to normal tissues. We also examined the mRNA expression level of the candidate gene product identified. Results We found that the DNA copy number abnormality of the chromosome 6q region is associated with TSCC metastasis. ZDHHC14 is on 6q25.3, a region gained in pN+ cases of TSCCs compared with pN− cases. Quantitative real-time reverse-transcription polymerase chain reaction showed that ZDHHC14 was overexpressed in all TSCC-derived cell lines compared with primary cultured NOKs at the mRNA level. Similar to the TSCC-derived cell lines, high frequencies of ZDHHC14 up-regulation were evident in mRNA levels of primary tumors ( n = 8/20, 40%). This up-regulation also is closely associated with lymph node status ( P = 0.0008). Conclusions These results suggested that ZDHHC14 expression may be correlated with lymph node metastasis and offers clues to the planning of new treatments such as early detection, prevention, and therapy for TSCC metastasis.

Clinical analysis of 35 cases second primary tongue squamous cell carcinoma after nasopharyngeal carcinoma radiotherapy

Objective To investigate the clinical features, effective treatment, survival and prognostic factors of second primary tongue squamous cell carcinoma (SPTSCC) after nasopharyngeal carcinoma (NPC) radiotherapy. Methods The clinical data of 35 cases with SPTSCC after NPC radiotherapy were analyzed retrospectively. Kaplan-Meier method, Log-Rank test and COX proportional hazard mode was performed for statistical analysis. Results 3-year and 5-year overall survival rates were 55 % and 47 %, respectively, lymph node metastasis rate was 5.71 %. Univariate analysis indicated that gender (χ2 = 8.89, P = 0.00), T classification (χ2= 5.58, P= 0.02), clinical stage (χ2 = 8.51, P= 0.04) and treatment methods (χ2 = 29.37, P = 0.00) were important factors of prognosis. Multivariate analysis showed that treatment methods (P = 0.00) and T classification (P = 0.03) were independent prognostic factors. Operative treatment group had better prognosis than the non-operative treatment group, the difference was statistically significant (P <0.05), male patients in the risk of SPTSCC was higher than the female patients, and the incidence of SPTSCC was increased along with extension of the time after NPC radiotherapy. Conclusion The rate of the lymph node metastasis is lower for SPTSCC after NPC radiotherapy and treatment patterns and T stage are independent prognostic factors. Long-term follow-up after NPC radiotherapy is necessary to the early diagnosis of SPTSCC, so that to give surgery or combined therapy with surgery in order to achieve a good effect. Key words: Nasopharyngeal neoplasms; Neoplasms,second primary; Tongue neoplasms

Deregulation of manganese superoxide dismutase (SOD2) expression and lymph node metastasis in tongue squamous cell carcinoma

BackgroundLymph node metastasis is a critical event in the progression of tongue squamous cell carcinoma (TSCC). The identification of biomarkers associated with the metastatic process would provide critical prognostic information to facilitate clinical decision making. Previous studies showed that deregulation of manganese superoxide dismutase (SOD2) expression is a frequent event in TSCC and may be associated with enhanced cell invasion. The purpose of this study is to further evaluate whether the expression level of SOD2 is correlated with the metastatic status in TSCC patients.MethodsWe first examined the SOD2 expression at mRNA level on 53 TSCC and 22 normal control samples based on pooled-analysis of existing microarray datasets. To confirm our observations, we examined the expression of SOD2 at protein level on an additional TSCC patient cohort (n = 100), as well as 31 premalignant dysplasias, 15 normal tongue mucosa, and 32 lymph node metastatic diseases by immunohistochemistry (IHC).ResultsThe SOD2 mRNA level in primary TSCC tissue is reversely correlated with lymph node metastasis in the first TSCC patient cohort. The SOD2 protein level in primary TSCC tissue is also reversely correlated with lymph node metastasis in the second TSCC patient cohort. Deregulation of SOD2 expression is a common event in TSCC and appears to be associated with disease progression. Statistical analysis revealed that the reduced SOD2 expression in primary tumor tissue is associated with lymph node metastasis in both TSCC patient cohorts examined.ConclusionsOur study suggested that the deregulation of SOD2 in TSCC has potential predictive values for lymph node metastasis, and may serve as a therapeutic target for patients at risk of metastasis.

Expression of Caveolin-1 in tongue squamous cell carcinoma by quantum dots

Quantum dots (QDs) are a new class of fluorescent probes to detect biomarker expression. The role of caveolin-1 (Cav-1) in tongue squamous cell carcinoma (TSCC) is still unknown. This study aimed to investigate the expression profile of Cav-1 in carcinogenesis and development of TSCC by QDs immunofluorescence histochemistry (QDs-IHC) and discuss the relationship between the Cav-1 expression and the clinicopathological outcomes. QDs-IHC was used to detect Cav-1 expression in tissue microarrays including normal tongue mucosa (NTM; n=10), hyperplastic tongue mucosa (HTM; n=10), tongue pre-cancer lesions (TPL; n=15) and primary tongue squamous cell carcinoma (PTSCC; n=61). Correlations between the Cav-1 expression and clinicopathologic variables were evaluated statistically. Cells positive for Cav-1 were clearly detected and bright images were obtained in a fine, granular pattern at the cell membrane and cytoplasm using QDs-IHC. The rate of Cav-1 immunoreactivity increased progressively from NTM (0%), HTM (0%), TPL (36%) to PTSCC (74%). When compared with each other, there was statistical significance among PTSCC, TPL and NTM as well as among PTSCC, TPL and HTM. Moreover, Cav-1 expression level in PTSCC was correlated positively with clinical stage and histologic grade. QDs-IHC could accurately detect protein location in tongue mucosa. An increased expression of Cav-1 in the stepwise carcinogenesis from NTM, HTM, TPL to PTSCC suggested that Cav-1 might be an oncogene in the development of tongue squamous cell carcinoma.