A Prognostic Model Based on Clinicopathological Features and Inflammation- and Nutrition-Related Indicators Predicts Overall Survival in Surgical Patients With Tongue Squamous Cell Carcinoma.

Objectives: It is reported that inflammation- and nutrition-related indicators have a prognostic impact on multiple cancers. Here we aimed to identify a prognostic nomogram model for prediction of overall survival (OS) in surgical patients with tongue squamous cell carcinoma (TSCC). Methods: The retrospective data of 172 TSCC patients were charted from the Cancer Hospital of Shantou University Medical College between 2008 and 2019. A Cox regression analysis was performed to determine prognostic factors to establish a nomogram and predict OS. The predictive accuracy of the model was analyzed by the calibration curves and the concordance index (C-index). The difference of OS was analyzed by Kaplan-Meier survival analysis. Results: Multivariate analysis showed age, tumor node metastasis (TNM) stage, red blood cell, platelets, and platelet-to-lymphocyte ratio were independent prognostic factors for OS, which were used to build the prognostic nomogram model. The C-index of the model for OS was 0.794 (95% CI = 0.729-0.860), which was higher than that of TNM stage 0.685 (95% CI = 0.605-0.765). In addition, decision curve analysis also showed the nomogram model had improved predictive accuracy and discriminatory performance for OS, compared to the TNM stage. According to the prognostic model risk score, patients in the high-risk subgroup had a lower 5-year OS rate than that in a low-risk subgroup (23% vs 49%, P < .0001). Conclusions: The nomogram model based on clinicopathological features inflammation- and nutrition-related indicators represents a promising tool that might complement the TNM stage in the prognosis of TSCC.

Prediction of lymph node metastasis in oral tongue squamous cell carcinoma using the neutrophil-to-lymphocyte ratio and platelet-to-neutrophil ratio.

BACKGROUND: Lymph node metastasis in a variety of tumors is associated with systemic inflammatory markers. However, this association has not been reported in oral tongue squamous cell carcinoma (OTSCC). This study aimed to investigate how the preoperative neutrophil-to-lymphocyte ratio (NLR) and platelet-to-neutrophil ratio (PNR) in OTSCC patients correlated with the occurrence of OTSCC and lymph node metastasis. METHODS: The data of 73 patients with primary OTSCC who underwent surgical resection were retrospectively analyzed. Patients with other malignant tumors, patients who had received radiotherapy or chemotherapy before surgery, and patients with active inflammation were excluded. The enrolled patients were divided into groups N0 (no early-stage lymph node metastasis) and N1 (early-stage lymph node metastasis). Venous blood samples were collected before surgery and at the third week after surgery and subjected to complete blood counting in a blood analyzer. Eighty-seven healthy people were included as a control group. In addition, the NLR and PNR in OTSCC patients were compared with those in the controls, and the postoperative NLR and PNR of group N0 were compared with those of group N1 . RESULTS: The NLR was significantly higher in the OTSCC patients than the controls (p < 0.05). The area under the receiver operating characteristic curve was 0.595. Further comparison of the NLR and PLR between group N0 and group N1 showed that when NLR was ≤1.622, and the probability of early-stage lymph node metastasis in OTSCC patients was 73.3%, and when PNR was >60.889, the probability was 86.7%. In re-examination 3 weeks postoperatively, the NLR and PNR were not significantly different between groups. CONCLUSION: The NLR has certain reference value for the diagnosis of OTSCC. The preoperative NLR and PNR can be used to predict early-stage lymph node metastasis in patients with histopathologically confirmed OTSCC.

LncRNA MALAT1 expression inhibition suppresses tongue squamous cell carcinoma proliferation, migration and invasion by inactivating PI3K/Akt pathway and downregulating MMP-9 expression.

OBJECTIVE: LncRNA MALAT1 has been proved to be involved in the development of various types of human cancers while the involvement of MALAT1 in tongue squamous cell carcinoma has not been reported. In view of this, our study aimed to investigate the functionality of MALAT1 in tongue squamous cell carcinoma. PATIENTS AND METHODS: The expression of MALAT1 in tumor tissues and adjacent healthy tissues of tongue cancer patients, and the serum from tongue cancer patients as well as healthy controls, were detected by quantitative Real Time-PCR (qRT-PCR). ROC curve analysis was performed to analyze the diagnostic value of plasma MALAT1 for tongue cancer. Survival curves were plotted using the Kaplan-Meier method to evaluate the prognostic value of plasma MALAT1 for tongue cancer. CCK-8 assay, transwell migration and invasion assay were performed to investigate the effects of MALAT1 knockdown on the proliferation, migration and invasion of tongue cancer cells, respectively. The effects of MALAT1 overexpression on the PI3K/Akt pathway and MMP-9 expression were detected by Western blot. RESULTS: The expression level of MALAT1 was remarkably higher in tumor tissues than that in adjacent healthy tissues. Serum MALAT1 was significantly higher in tongue cancer patients than in healthy controls. MALAT1 knockdown markedly inhibits the proliferation, migration and invasion of tongue cancer cells. MALAT1 knockdown also reduced the phosphorylation level of Akt as well as the expression level of MMP-9. It showed no significant effects on Akt expression, while PI3K activator treatment reduced the inhibitory effects of MALAT1 knockdown on the proliferation, migration and invasion of tongue cancer cells. CONCLUSIONS: LncRNA MALAT1 expression inhibition can inhibit the proliferation, migration and invasion of tongue cancer cells by inactivating the PI3K/Akt pathway and downregulating MMP-9. MALAT1 may serve as a target for the treatment of tongue squamous cell carcinoma.

Prognostic Significance of Pretreatment Lymphocyte-to-Monocyte Ratio in Patients with Tongue Cancer.

BACKGROUND/AIM: Low pre-operative lymphocyte-to-monocyte ratio (LMR) is associated with worse outcomes in several malignancies. The aim of this study was to determine the prognostic value of LMR in tongue cancer. MATERIALS AND METHODS: A total of 103 patients with pathologically-proven tongue cancer were retrospectively analyzed. The peripheral LMR and the ratio of CD8-positive to CD14-positive (CD8+/CD14+) tumor-infiltrating cells were determined by immunohistochemical staining. Receiver operating characteristic curve analysis, log-rank test, and Cox proportional hazards regression models were used for statistical analysis. RESULTS: There was a significant difference in overall survival (OS) between low LMR and high LMR, and low CD8+/CD14+ tumor-infiltrating cells and high CD8+/CD14+ tumor infiltrating cells. For the clinical analysis, multivariate analysis showed that clinical ocular inspection type and low LMR were independent predictors for poor OS. Concerning the immunohistochemical analysis, monocyte count was independent predictor of poor OS. CONCLUSION: Pre-operative LMR and CD8+/CD14+ tumor-infiltrating cells serve as independent prognostic biomarkers.

Tongue Cancer Patients Can be Distinguished from Healthy Controls by Specific N-Glycopeptides Found in Serum.

PURPOSE: There are no blood biomarkers to detect early-stage oral cavity squamous cell carcinoma (OSCC) prior to clinical signs. Most OSCC incidence is associated with significant morbidity and poor survival. The authors aimed to use mass-spectrometry (MS) technology to find specific N-glycopeptides potentially serving as serum biomarkers for preclinical OSCC screening. EXPERIMENTAL DESIGN: Serum samples from 14 patients treated for OSCC (stage I or stage IV) with 12 age- and sex-matched controls are collected. Quantitative label-free N-glycoproteomics is performed, with MS/MS analysis of the statistically significantly different N-glycopeptides. RESULTS: Combined with a database search using web-based software (GlycopeptideID), MS/MS provided detailed N-glycopeptide information, including glycosylation site, glycan composition, and proposed structures. Thirty-eight tryptic N-glycopeptides are identified, having 19 unique N-glycosylation sites representing 14 glycoproteins. OSCC patients, including stage I tumors, can be differentiated from healthy controls based on the expression levels of these glycoforms. N-glycopeptides of IgG1, IgG4, haptoglobin, and transferrin have statistically significant different abundances between cases and controls. CONCLUSIONS AND CLINICAL RELEVANCE: The authors are the first to suggest specific N-glycopeptides to serve as potential serum biomarkers to detect preclinical OSCC in patients. These N-glycopeptides are the lead candidates for validation as future diagnostic modalities of OSCC as early as stage I.

Rescue of iCIKs transfer from PD-1/PD-L1 immune inhibition in patients with resectable tongue squamous cell carcinoma (TSCC).

OBJECTIVES: The purpose of this study is to evaluate the therapeutic efficacy and the role of PD-1/PD-L1 pathway in tongue squamous cell carcinoma (TSCC) patients treated with radical operation combined with chemotherapy and improving cytokine induced killer cells (iCIKs) transfer. METHODS: Thirteen patients who received radical resection and chemotherapy were enrolled in this study. PD-1/PD-L1 expression was evaluated in TSCC patients. ICIKs were cultured from patient-derived peripheral blood mononuclear cells (PBMCs) in vitro. The immunological differences underlying iCIKs transfer were investigated through phenotype, cytokine secretion and PD-1/PD-L1 inhibition analysis. RESULTS: The serum PD-L1 levels were elevated in the TSCC patients. PD-L1 was detected on both human TSCC cells and tumour tissue sections. PD-1 expression was much higher on the PBMCs of TSCC patients than on in vitro cultured iCIKs. Interruption of PD-1/PD-L1 interaction enhanced the cytotoxicity of iCIKs in vitro. CD3 + CD8+ T cell proportion and cytokine IL-6 secretion decreased after chemotherapy. The infusion of iCIKs effectively reversed the immunosuppression through the upregulation of the CD3 + CD8+ T cell proportion and Th cell cytokine secretion (IFN-γ, TNF-α, IL-4 and IL-6). Twelve responders are currently alive (95.7+ months), another patient 83 months. CONCLUSION: Our findings indicated that the PD-1/PD-L1 interaction contributes to the immunosuppression in TSCC patients. ICIKs transfer is an effective therapy to reverse the immunosuppression caused by surgical procedures and chemotherapy and improve immune system function.

HSP27-Mediated Extracellular and Intracellular Signaling Pathways Synergistically Confer Chemoresistance in Squamous Cell Carcinoma of Tongue.

Purpose: Squamous cell carcinoma of tongue (SCCT) is the most common type of oral cavity carcinoma. Chemoresistance in SCCT is common, and the underlying mechanism remains largely unknown. We aimed to identify key molecules and signaling pathways mediating chemoresistance in SCCT.Experimental Design: Using a proteomic approach, we found that the HSP27 was a potential mediator for chemoresistance in SCCT cells. To further validate this role of HSP27, we performed various mechanistic studies using in vitro and in vivo models as well as serum and tissue samples from SCCT patients.Results: The HSP27 protein level was significantly increased in the multidrug-resistant SCCT cells and cell culture medium. Both HSP27 knockdown and anti-HSP27 antibody treatment reversed chemoresistance. Inversely, both HSP27 overexpression and recombinant human HSP27 protein treatment enhanced chemoresistance. Moreover, chemotherapy significantly induced HSP27 protein expression in both SCCT cells and their culture medium, as well as in tumor tissues and serum of SCCT patients. HSP27 overexpression predicts a poor outcome for SCCT patients receiving chemotherapy. Mechanically, extracellular HSP27 binds to TLR5 and then activates NF-κB signaling to maintain SCCT cell survival. TLR5 knockdown or restored IκBα protein level disrupts extracellular HSP27-induced NF-κB transactivation and chemoresistance. Moreover, intracellular HSP27 binds to BAX and BIM to repress their translocation to mitochondrion and subsequent cytochrome C release upon chemotherapy, resulting in inhibition of the mitochondrial apoptotic pathway.Conclusions: HSP27 plays a pivotal role in chemoresistance of SCCT cells via a synergistic extracellular and intracellular signaling. HSP27 may represent a potential biomarker and therapeutic target for precision SCCT treatment. Clin Cancer Res; 24(5); 1163-75. ©2017 AACR.

Oral squamous cell carcinoma patients can be differentiated from healthy individuals with label-free serum proteomics.

BACKGROUND: No blood biomarkers to detect early oral cavity squamous cell carcinoma (OSCC) without clinical signs exist - diagnosis is solely based on histology of a visible tumour. Most OSCC patients are diagnosed at advanced stage, which leads to significant morbidity and poor survival. Our aim was to find the serum screening or detection biomarkers in OSCC. METHODS: Serum samples from patients with OSCC treated at the Department of Otorhinolaryngology - Head and Neck Surgery, Helsinki University Hospital (Finland) were collected. Age- and gender-matched healthy individuals served as controls. Quantitative label-free proteomics in high definition MSE mode(HDMSE) was performed on 13 patients and 12 healthy samples. Various statistical analyses were performed on quantitative proteomics data to obtain the most influential proteins, which classify the patients vs healthy samples. RESULTS: In quantitative proteomic analysis (HDMSE), 388 proteins were quantified in our pilot study. A complete separation between cases and controls was seen in supervised and unsupervised classification techniques such as orthogonal projections on latent structure-discriminant analysis (OPLS-DA) and self-organising maps. Using OPLS-DA S-plot, we identified a set of eight proteins that completely separated OSCC patients from healthy individuals. CONCLUSIONS: Although the tumour stages varied from I to IVa, these potential biomarkers were able to identify all OSCCs demonstrating their sensitivity to detect tumours of all stages. We are the first to suggest a set of serum biomarkers in our pilot study to be evaluated further as a diagnostic panel to detect preclinical OSCC in risk patients.

Low Pretreatment Lymphocyte-Monocyte Ratio and High Platelet-Lymphocyte Ratio Indicate Poor Cancer Outcome in Early Tongue Cancer.

PURPOSE: The white blood cell (WBC) indices have been reported to have a prognostic impact in cancer of multiple organs including head and neck cancer; however; site and stage stratification was not attempted, and compelling evidence has shown that early cancers have a different distribution and prognostic ability than late-stage cancers. We studied the prognostic importance of WBC indices in early oral tongue cancers. PATIENTS AND METHODS: The retrospective data of primary pT1N0 to pT2N0 oral tongue cancers treated between 2009 and 2013 were charted. WBC indices such as the neutrophil count, lymphocyte count (LC), platelet count (PC), and monocyte count, along with derived indices such as the neutrophil-lymphocyte ratio, platelet-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio (LMR), were analyzed by multivariate analysis with other clinicopathologic prognostic factors. RESULTS: A total of 133 patients fulfilled the inclusion criteria; the minimum follow-up period for living patients was 36 months. A total of 22 patients reported disease relapse, and 11 patients died of disease. Multivariate analysis showed LC (hazard ratio [HR], 0.206; 95% confidence interval [CI], 0.092 to 0.46; P < .001), PC (HR, 1.011; 95% CI, 1.001 to 1.021; P = .026), PLR (HR, 1.012; 95% CI, 1.008 to 1.016; P < .001), and LMR (HR, 0.721; 95% CI, 0.596 to 0.872; P = .001) are significant independent prognostic factors for disease-free survival. Distant metastasis (HR, 9.014; 95% CI, 2.303 to 38.914; P = .004), LC (HR, 0.091; 95% CI, 0.015 to 0.558; P = .01), PC (HR, 1.023; 95% CI, 1.006 to 1.041; P = .009), PLR (HR, 1.016; 95% CI, 1.004 to 1.027; P = .002), and LMR (HR, 0.58; 95% CI, 0.387 to 0.868; P = .008) are significant independent prognostic factors for overall survival. CONCLUSIONS: Low pretreatment LMR and high PLR indicate poor survival in patients with early tongue cancer. We suggest close follow-up for this subgroup despite radical resection with clear margins.

Interleukin-17A promotes tongue squamous cell carcinoma metastasis through activating miR-23b/versican pathway.

Interleukin-17A (IL-17A), a proinflammatory cytokine mainly produced by T helper 17 cells, exerts protumor or antitumor effects in different cancer entities. However, the exact role of IL-17A in carcinogenesis and progression of tongue squamous cell carcinoma (TSCC) remains unclear. Here, we found that the levels of IL-17A in serum and tumor samples were significantly increased in TSCC patients and positively correlated with tumor metastasis and clinical stage. Besides, IL-17A enhanced cell migration and invasion in SCC15, a TSCC cell line. Furthermore, IL-17A inversely correlated with miR-23b expression in TSCC specimens. In vitro, NF-κB inhibited miR-23b transcription by directly binding to its promoter region. IL-17A downregulated miR-23b expression via activating NF-κB signaling pathway characterized by increasing p65 expression in the nuclear and elevating the levels of p-IKKα and p-IκBα. Overexpression of miR-23b inhibited, whereas knockdown of miR-23b promoted migration and invasion abilities of SCC15 cells. Moreover, extracellular matrix protein versican was proved to be the direct target of miR-23b through luciferase assay. IL-17A increased versican levels in vitro and knockdown of versican by siRNA inhibited SCC15 cell migration and invasion. Taken together, these results reveal a novel mechanism that IL-17A in TSCC microenvironment promotes the migration and invasion of TSCC cells through targeting miR-23b/versican pathway.

Tongue squamous cell carcinoma producing both parathyroid hormone-related protein and granulocyte colony-stimulating factor: a case report and literature review.

BACKGROUND: Paraneoplastic syndrome generally results from tumor-derived hormones or peptides that cause metabolic derangements. Common metabolic conditions include hyponatremia, hypercalcemia, hypoglycemia, and Cushing's syndrome. Herein, we report a very rare case of tongue carcinoma presenting with leukocytosis and hypercalcemia. CASE PRESENTATION: A 57-year-old man was admitted to our hospital with tongue squamous cell carcinoma (cT4aN0M0, stage IV). He underwent radical resection following preoperative chemoradiotherapy, but locoregional recurrence was detected 2 months after surgery. He presented with marked leukocytosis and hypercalcemia with elevated serum levels of granulocyte colony-stimulating factor (G-CSF) and parathyroid hormone-related protein (PTHrP). He was therefore managed with intravenous fluids, furosemide, prednisolone, elcatonin, and pamidronate. However, the patient died 1 month later of carcinomatous pleuritis following distant metastasis to the lung. Immunohistochemical analyses of the resected specimens revealed positive staining for PTHrP and G-CSF in the cancer cells. CONCLUSIONS: In this case, it was considered that tumor-derived G-CSF and PTHrP caused leukocytosis and hypercalcemia.

The effect of preoperative neutrophil, platelet and lymphocyte counts on local recurrence and survival in early-stage tongue cancer.

The aim of this study was to investigate the predictive value of preoperative neutrophil, platelet and lymphocyte counts in local recurrence and survival in the patients operated for early-stage squamous cell carcinoma (SCC) of the tongue. 57 patients who underwent surgery for early-stage (stage 1-2) SCC of the tongue were enrolled in the study. Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and neutrophil × PLR value (N × PLR) were used as outcome measures. Local recurrence was detected in 11 (19.3 %) patients during follow-up period. Mortality was seen in 7 (12.3 %) patients. 37 (64.9 %) patients had stage 1 and 20 (35.1 %) patients had stage 2 tumor. NLR, PLR and N × PLR cutoff values were determined as 2.26, 146,855 and 689,912, respectively, by receiver operating characteristic analysis. The relationship between NLR, PLR, N × PLR and local recurrence was statistically significant according to these cutoff values (p values 0.021, 0.020, 0.017, respectively). We suggest that NLR, PLR and N × PLR may be used to predict local recurrence, while their use in overall and disease-free survival is limited. Further studies involving large patient groups are required.

Reduced serum levels of syndecan-1 in patients with tongue squamous cell carcinoma.

OBJECTIVES/HYPOTHESIS: To investigate soluble syndecan-1 (Sdc-1) in the sera of patients with tongue squamous cell carcinoma (SCC) and its correlation with the histopathological criteria of tumors. STUDY DESIGN: In a case-control study using a convenient method of sampling, 18 female and 25 male patients with confirmed diagnosis of tongue SCC, and 19 healthy females and 27 males were studied. METHODS: Soluble Sdc-1 was measured in the sera of 43 patients with tongue SCC and was compared with that of healthy age-/sex-matched controls using a commercial enzyme-linked immunosorbent assay. Clinical and pathological data, along with the demographic characteristics of the patients, were recorded at the time of sampling. RESULTS: The levels of soluble Sdc-1 were decreased in the sera of patients compared to controls (91.17 ± 88.60 vs. 158.17 ± 103.47 ng/mL, P = .002). Although patients who smoke tended to have higher grades (P = .043), there was no significant difference in the level of syndecan-1 between smokers and non-smokers. A significant difference between syndecan-1 in the sera of patients with tumors of different stages was observed (Kruskal-Wallis test P=0.039); however, scarcity of patients in stages I and III decreased the power of the comparison. CONCLUSIONS: Sdc-1 levels in the sera of patients do not correlate with the tumor progression in the tongue SCC. This is in contrast with the reported inverse correlation between the expression level of membranous Sdc-1 and the histological grade and size of head and neck tumors. Therefore, Sdc-1 shedding may not be a major mechanism in the progressive loss of its expression regarding tongue tumor. LEVEL OF EVIDENCE: NA Laryngoscope, 126:E191-E195, 2016.

Downregulation of miRNA-424: a sign of field cancerisation in clinically normal tongue adjacent to squamous cell carcinoma.

BACKGROUND: The overall survival for patients with squamous cell carcinoma of the tongue is low and the search for early diagnostic and prognostic markers is thus essential. MicroRNAs have been suggested as potential prognostic and diagnostic candidates in squamous cell carcinoma of head and neck in general. METHODS: On the basis of the known differences between sub-sites within the oral cavity, we investigated the expression and role of microRNA-424 in squamous cell carcinoma arising in tongue. MicroRNA levels were measured by qRT-PCR in both tissue and plasma samples. RESULTS: Levels of microRNA-424 were upregulated in tongue squamous cell carcinoma, but not in tumours originating from gingiva or floor of the mouth. Interestingly, microRNA-424 was downregulated in clinically normal tongue tissue next to tumour compared with completely healthy tongue, indicating that microRNA-424 could be a marker of field cancerisation in this tumour type. However, expression of microRNA-424 in a tongue-derived epithelial cell line revealed no significant changes in the expression profile of proteins and genes. CONCLUSIONS: Our patient data show that microRNA-424 alterations are a marker of field cancerisation specific for tongue tumourigenesis, which also could have a role in development of tongue squamous cell carcinoma.

Serum and Saliva MMP-3 in Patients with OLP and Oral SCC.

BACKGROUND: Matrix metalloproteinase-3 (MMP-3) plays a key role in development of cancer. The purpose of this study was to assess MMP-3 in the serum and saliva of patients with oral lichen planus (OLP) and oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Thirty patients with OLP (8 reticular and 22 erosive forms), and 20 patients with OSCC (6 in low stage and 14 in advanced stage), were enrolled in this study, conducted at the Cancer Department, Clinic of Oral Medicine, Tehran University of Medical Sciences. The serum and saliva MMP-3 was assayed by ELISA method. Statistical analysis of the Student's t-test, ANOVA and Pearson correlation coefficient was performed. The mean saliva and serum levels of MMP-3 were significantly higher in patients with OSCC compared with OLP. RESULTS: The serum and saliva MMP-3 concentrations increased from reticular form of OLP to erosive form of OLP, and increased further to low stage of OSCC and advanced stage of OSCC. Serum MMP-3 correlated significantly with unstimulated (r = 0.310, p = 0.038) and stimulated (r = 0.365, p < 0.026) saliva MMP-3. CONCLUSION: Serum and saliva MMP-3 levels appear associated with OLP and OSCC.

Elevated carcinoembryonic antigen tumour marker caused by head and neck cancer: a case report and literature study.

Carcinoembryonic antigen is a tumour marker commonly increased in gastrointestinal and pulmonary cancers. We report a case of a 46-year-old man with a mucoepidermoid carcinoma of the base of tongue with an elevated and traceable serum carcinoembryonic antigen level. This antigen proved to be a valuable marker in the treatment follow-up. When a raised carcinoembryonic antigen level is found, salivary gland malignancies should be taken into the differential diagnosis and clinical examination of the head and neck region should not be overlooked.

Prognostic value of pretreatment circulating neutrophils, monocytes, and lymphocytes in oropharyngeal cancer stratified by human papillomavirus status.

BACKGROUND: The objective of this study was to investigate the prognostic value of the pretreatment circulating neutrophil count (CNC), circulating monocyte count (CMC), and circulating lymphocyte count (CLC) in human papillomavirus (HPV)-related (HPV+) and HPV-unrelated (HPV-) oropharyngeal cancer (OPC). METHODS: All p16-confirmed HPV+ and HPV- OPC cases treated with chemoradiotherapy from 2000 to 2010 were included. Overall survival (OS) and recurrence-free survival (RFS) were compared for high and low CNCs, CMCs, and CLCs (dichotomized by median values). A multivariate analysis (MVA) confirmed their prognostic value in HPV+ and HPV- tumors, respectively. RESULTS: Five hundred ten HPV+ OPC cases and 192 HPV- OPC cases were included. The HPV+ cohort had lower CNC and CMC values but a CLC similar to that of the HPV- patients (P < .01). The median follow-up was 4.8 years. In the HPV+ cohort, a high CNC or CMC correlated with reduced OS and RFS in comparison with a low CNC or CMC (P < .01 for all), but no difference was evident in OS (P = .30) or RFS (P = .10) with the CLC. MVA confirmed that a higher CNC or CMC independently predicted lower OS (hazard ratio [HR] for CNC, 1.14, P < .01; HR for CMC, 2.95, P < .01) and lower RFS (HR for CNC, 1.11, P < .01; HR for CMC, 3.39, P < .01), whereas a higher CLC was associated with higher RFS (HR, 0.66, P = .03) and marginally higher OS (HR, 0.80, P = .08). In the HPV- cohort, CNC, CMC, and CLC were not predictive of OS (P = .16, P = .86, and P = .14) or RFS (P = .61, P = .59, and P = .62). CONCLUSIONS: This relatively large cohort study demonstrates that a high CNC and a high CMC independently predict inferior OS and RFS, whereas a high CLC predicts better RFS and marginally better OS in HPV+ OPC patients. This association was not apparent in HPV- patients.

Preoperative plasma fibrinogen predicts cervical metastasis in patients with stage I/II carcinoma of the tongue.

The aim of this study was to evaluate the association of preoperative plasma fibrinogen levels with clinico-pathological parameters and disease-free survival in patients with oral tongue squamous cell carcinoma (OTSCC). We retrospectively studied 76 patients with OTSCC who underwent a partial glossectomy only, at a single centre, between 1996 and 2007. Among the 76 patients, 30 eventually developed cervical metastasis. Preoperative plasma fibrinogen levels were determined and correlated with clinico-pathological findings by t-test or analysis of variance methods. Univariate and multivariate analyses were used to determine the association of preoperative plasma fibrinogen levels and disease-free survival. Elevated levels of plasma fibrinogen were positively related with growth type (P<0.001), differentiation (P<0.001), thickness (P<0.001), and the infiltrative growth ratio (P=0.032). Univariate analysis showed that growth type (P<0.001), differentiation (P<0.001), thickness (P<0.001), and preoperative plasma fibrinogen levels (P<0.001) were significantly correlated with disease-free survival. Multivariate analysis showed that the plasma fibrinogen level remained an independent factor for disease-free survival after partial glossectomy for OTSCC (P=0.029). A high preoperative plasma fibrinogen level is an independent predictor of cervical metastasis after partial glossectomy for OTSCC. A conservative supraomohyoid neck dissection is appropriate in patients with stage I/II carcinoma of the tongue whose preoperative plasma fibrinogen is >300 mg/dl.

Relation of erythrocyte indices and serum iron level with clinical and histological progression of oral squamous cell carcinoma in Central India.

AIM: This study aims to evaluate the relation of erythrocyte indices and serum iron level with clinical and histopathological progression of oral squamous cell carcinoma (OSCC). METHODS: Eighty newly diagnosed OSCC patients recruited for the study were divided according to tumor size int three groups. Erythrocyte indices (e.g., hemoglobin [Hb], red blood cell [RBC] count, packed cell volume [PCV]) and serum iron level (S.Fe) were evaluated with normal reference values, control subject, primary tumor size and histopathological grading. Correlation of Hb to S.Fe was also analyzed. RESULTS: We found that 56.36, 61.81, and 83.63% of males and 76, 32, and 88% of female patients were anemic in terms of Hb%, RBC count and PCV respectively, whereas the remainding indices and S.Fe were within normal range (P < 0.05). Percent Hb, RBC count and PCV gradually decreased with increasing tumor size and histopathological grading (P > 0.05). Moderate to weak correlation was observed between Hb and S.Fe (P < 0.05). CONCLUSIONS: Tumor-induced hemolysis appeared to be responsible for anemia in OSCC and its severity increased with the progression of tumor. Moderate to weak correlation exists between Hb and S.Fe probably owing to the dual requirement of iron for bone marrow and the tumor.

Decreased adiponectin level is associated with aggressive phenotype of tongue squamous cell carcinoma.

Circulating adiponectin levels are inversely associated with risk of various obesity-related cancers. However, the effect of adiponectin on carcinogenesis and progression of tongue squamous cell carcinoma (TSCC) remains unknown. We measured serum adiponectin levels in 59 patients with TSCC and 50 healthy controls. Expression of adiponectin and its receptors in paired tumor and paracancerous specimens were determined by immunohistochemical staining (n = 37) and western blot (n = 30), respectively. Serum adiponectin level was lower in patients than in controls (5.0 ± 2.4 vs 8.4 ± 3.5 µg/mL, P < 0.01), and was inversely associated with histological grade and lymph node metastasis but not tumor size. Local adiponectin levels in tumor tissue gradually decreased as tumor-node-metastasis stage increased, while the expression of adiponectin receptors was unchanged. In addition, serum adiponectin levels in the TSCC patients without metabolic and cardiovascular diseases, or without smoking and drinking habits, were still lower than in controls. Furthermore, adiponectin inhibited the migration, but not proliferation, of SCC15 cells in vitro. These results indicate that a decreased adiponectin level is associated with risk of TSCC. Hypoadiponectinemia might be used as a biomarker to predict an aggressive phenotype of TSCC.