Perineural invasion, lactate dehydrogenase, globulin, and serum sodium predicting occult metastasis in oral cancer.

OBJECTIVE: This study aimed to develop a nomogram to predict the neck occult metastasis in early (T1-T2 cN0) oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: The nomogram was developed in a training cohort of 336 early OSCC patients and was validated in a validation cohort including 88 patients. Independent predictors were calculated by univariate and multivariate logistic regression analyses. RESULTS: In univariate logistical regression analysis, gender, perineural invasion (PNI), blood vessel invasion, mean corpuscular hemoglobin, aspartate aminotransferase, prealbumin, globulin (GLO), lactate dehydrogenase (LDH), serum sodium (NA), and serum chloride were significant associated with neck occult metastasis. Multivariate logistical regression analysis identified PNI (p < .001), LDH (p = .003), GLO (p = .019), and NA (p = .020) as independent predictors of neck occult metastasis. Cut-off values for LDH, GLO, and NA obtained from AUC were 142.5, 26.35, and 139.5, respectively. The nomogram based on PNI and categorical GLO, LDH, and NA exhibited a strong discrimination, with a C-indexes of 0.748 (95%CI = 0.688 to 0.810) in the training cohort and 0.751 (95%CI = 0.639 to 0.863) in the validation cohort. CONCLUSIONS: A nomogram based on PNI, LDH, GLO, and NA for predicting the risk of neck lymph nodes occult metastasis in OSCC could help surgeons with therapy decision-making.

Cytoplasmic eIF6 promotes OSCC malignant behavior through AKT pathway.

BACKGROUND: Eukaryotic translation initiation factor 6 (eIF6), also known as integrin ß4 binding protein, is involved in ribosome formation and mRNA translation, acting as an anti-association factor. It is also essential for the growth and reproduction of cells, including tumor cells. Yet, its role in oral squamous cell carcinoma (OSCC) remains unclear. METHODS: The expression characteristics of eIF6 in 233 samples were comprehensively analyzed by immunohistochemical staining (IHC). Effects of eIF6 over-expression and knockdown on cell proliferation, migration and invasion were determined by CCK-8, wound healing and Transwell assays. Western blot, immunofluorescence (IF) and co-immunoprecipitation (co-IP) were performed for mechanical verification. RESULTS: We found that cytoplasmic eIF6 was abnormally highly expressed in OSCC tissues, and its expression was associated with tumor size and the clinical grade. Amplification of eIF6 promoted the growth, migration and invasion capabilities of OSCC cell lines in vitro and tumor growth in vivo. Through Western blot analysis, we further discovered that eIF6 significantly promotes epithelial-mesenchymal transformation (EMT) in OSCC cells, while depletion of eIF6 can reverse this process. Mechanistically, eIF6 promoted tumor progression by activating the AKT signaling pathway. By performing co-immunoprecipitation, we discovered a direct interaction between endogenous eIF6 and AKT protein in the cytoplasm. CONCLUSION: These results demonstrated that eIF6 could be a new therapeutic target in OSCC, thus providing a new basis for the prognosis of OSCC patients in the future. Video abstract.

MiR-34a inhibits the proliferation, migration, and invasion of oral squamous cell carcinoma by directly targeting SATB2.

In various kinds of carcinomas, the special AT-rich sequence-binding protein 2 (SATB2) with its atypical expression promotes the metastasis and progression of the tumor, though in the oral squamous cell carcinoma (OSCC) its inherent mechanism and the status of SATB2 remain unclear. The role played by the SATB2 expression in the OSCC cell lines and tissue samples in the target of miR-34a downstream is the intended endeavor of this study. In te OSCCs the miR-34a expression was determined by quantitative real-time polymerase chain reaction (q-PCR), while the SATB2 expression in the cell lines and tissue samples in OSCC was analyzed with the q-PCR and the western blot. Studies in both in vitro and in vivo of the effects of miR-34a on the initiation of OSCC were conducted. As a direct target of the miR-34a the SATB2 was verified with the luciferase reporter assay. In cases where the miR-34a levels were low, the SATB2 in OSCCs seemed to be overexpressed. Besides, both in the in vitro and in vivo a suppression of migration, invasion, and cell growth was caused by miR-34a by down regulating the SATB2 expression. The SATB2 being a direct target of miR-34a was confirmed by the cotransfection of miR-34a mimics specifically the decrease in the expression of luciferase of SATB2-3'UTR-wt reporter. As a whole, our study confirmed the inhibition of miR-34a in the invasion, proliferation, and migration of the OSCCs, playing a potential tumor suppressor role with SATB2 as its downstream target.

Neoadjuvant dose-modified docetaxel in squamous cell carcinoma of the head and neck: A phase 3 study.

OBJECTIVE: To evaluate the efficacy and safety of dose-modified docetaxel plus cisplatin and 5-fluorouracil (TPF) in Chinese patients with squamous cell carcinoma of the head and neck (SCCHN). MATERIALS AND METHODS: This Phase III, open-label, multi-center study included Chinese adults with previously untreated TNM Stage III or IV SCCHN (NCT00995293). Patients were randomized (1:1) to induction chemotherapy with TPF (docetaxel 60 mg/m2 and cisplatin 60 mg/m2 on day 1 and 5-FU 750 mg/m2  per day continuous IV infusion on days 1-5) or PF (cisplatin 75 mg/m2 on day 1 and 5-FU 750 mg/m2  per day on days 1-5) every 3 weeks for 3-4 cycles. The primary endpoint was progression-free survival (PFS). RESULTS: Median PFS in the TPF (n = 108) and PF (n = 111) groups was 400 days and 342 days (HR = 0.75; 95% CI, 0.53─1.06; p = .227), respectively. Overall response rate was higher for TPF versus PF (76.3% vs. 52.9%; p = .001), although this equalized following radiotherapy (75.0% vs. 73.9%). In the TPF and PF groups, ≥1 treatment-emergent adverse event was experienced by 104 (94.5%) and 110 (93.2%) patients, respectively. CONCLUSION: Adding dose-modified docetaxel to PF did not significantly improve PFS but may increase anti-tumor activity in Chinese patients with locally advanced SCCHN.

Membrane-tethered Notch1 exhibits oncogenic property via activation of EGFR-PI3K-AKT pathway in oral squamous cell carcinoma.

Notch proteins are highly conserved cell surface receptors which play essential roles in cellular differentiation, proliferation, and apoptotic events at all stages of development. Recently, NOTCH1 mutations have been extensively observed in oral squamous cell carcinoma (OSCC) and are hinted to be Notch1-inactivating mutations. However, little is known about the biological effect of these reported mutations in OSCC. To mimic the inactivation of Notch1 due to inappropriate mutations and to determine the potential mechanisms, we utilized wild-type Notch1 vectors (Notch1WT ) or mutant Notch1 vectors (Notch1V1754L ) to transfect into OSCC cell lines. Membrane-tethered Notch1 induced by mutation was analyzed by immunofluorescence staining. γ-Secretase inhibitor PF-03084014 was utilized to determine the phenotype in the absence of endogenous Notch1 activation. Here we demonstrated that membrane-tethered Notch1 inactivated the canonical Notch1 signaling and oncogenic phenotypes were identified by promoting cell proliferation and invasion and by inducing epithelial-to-mesenchymal transition in cells. The γ-secretase inhibitor PF-03084014 also showed distinct oncogenic property after treatment. Importantly, both membrane-tethered Notch1 and PF-03084014 inhibitor activated the epidermal growth factor receptor (EGFR)-phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT) signaling pathway, which has been confirmed as an overwhelming modulator in OSCC. This was the first time that we clearly simulated the mutated Notch1 activities and determined the oncogenic phenotypes of membrane-tethered Notch1. Compared with wild-type Notch1, membrane-tethered Notch1 was strongly associated with activated EGFR-PI3K-AKT signaling pathway.

Prognostic value of serum liver enzymes in oral and oropharynx squamous cell carcinomas.

BACKGROUND: Serum liver enzymes, which catalyze relevant catabolic pathways, have been indicated to be diagnostic and prognostic tools for several malignant tumors. The correlation between serum liver enzymes levels and survival in patients with oral and oropharynx squamous cell carcinomas (OSCC) is still absent. Here, we conducted a study focusing on predictive value of serum liver enzymes in terms of prognosis in the patients. METHODS: A retrospective study including 134 OSCC patients from years 2009 to 2014 was performed to investigate the association between levels of pre-treatment serum liver enzymes, various clinical parameters and prognostic outcomes, which are overall survival (OS) and disease-free survival (DFS). Log-rank tests with Kaplan-Meier method were used to detect potential prognostic biomarkers. Multivariate analyses by Cox proportional hazards model were used to identify significant predictors of prognosis. RESULTS: Serum adenosine deaminase (ADA) level was associated with patients' OS and DFS by univariate analyses (P = 0.006 and P = 0.024, respectively). Multivariate analyses showed that higher serum ADA (>17.2 U/L) (P = 0.019) as well as positive lymph node status (P = 0.035) independently predicted worse OS of patients with OSCC. In addition, older age (≥60 years) (P = 0.043) and positive lymph node status (P = 0.027) were independently prognostic parameters for poorer DFS. CONCLUSIONS: Pre-operative serum ADA levels may serve as a reliable independent prognostic predictor for OS in OSCC patients.

Effect of verbascoside on apoptosis and metastasis in human oral squamous cell carcinoma.

Despite significant advances in therapy, the 5-year survival rates for patients with advanced stage oral cancers still remains poor as an appropriate treatment has not been found yet, due to side effects of chemo/radiotherapy. Verbascoside (VB), a major bioactive constituent of the Tsoong herb, displays pharmacological properties by exhibiting anti-oxidative, anti-inflammatory and anti-cancer activities. However, the underlining function and mechanism of VB in human oral squamous cell carcinoma (OSCC) remains unclear. In this study, we show that VB significantly decreased the viability and metastasis of HN4 and HN6 tumor cells, while promoting apoptosis. A xenograft OSCC mouse model further showed that intraperitoneal injection of VB strongly inhibited growth and lung metastasis of implanted tumor cells. Immunoblot analysis confirmed that VB effectively suppressed nuclear factor (NF)-κB activation and downstream Bcl-2/Bcl-XL expression, resulting in increased OSCC cell apoptosis. In addition, VB suppressed mRNA and protein expression of matrix metalloproteinase-9 via suppression of NF-κB activation, thereby inhibiting tumor cell metastasis. Inspiringly, compared to cisplatin-treated group, VB is a biocompatible agent without signficant side effects in vivo. Collectively, our results demonstrate that VB effectively inhibits OSCC tumor cell growth and metastasis via suppression of IκB kinase complex (IKK)/NF-κB-related signaling activation, suggesting that VB has potential use as a potent anticancer agent in OSCC therapeutic strategies.

A novel Notch1 missense mutation (C1133Y) in the Abruptex domain exhibits enhanced proliferation and invasion in oral squamous cell carcinoma.

BACKGROUND: Notch1 has been regarded as a fundamental regulator in tissue differentiation and stem cell properties. Recently, Notch1 mutations have been reported intensively both in solid tumors and in hematopoietic malignancies. However, little is known about the biological effect and the clinical implication of these reported mutations. Previously, we discovered several missense mutations in the Notch1 receptor in a Chinese population with oral squamous cell carcinoma (OSCC). METHODS: We selected a 'hotspot' mutation in the Abruptex domain (C1133Y). The expression of Notch1 was determined by western blot and real-time qPCR in OSCC cell lines transfected with pcDNA3.1-Notch1WT, pcDNA3.1-Notch1C1133Y, or pcDNA3.1 empty vector. CCK-8 assays were used to assess cell proliferation. Flow cytometry and western blot were used to confirm the alteration of cell cycle after transfection. Transwell assays and the detection of Epithelial-to-mesenchymal transition (EMT) markers were used to determine the invasive ability. The effects of Notch1 C1133Y mutation were analyzed by Immunofluorescence staining and the expression of EGFR-PI3K/AKT signaling. RESULTS: We demonstrated that Notch1C1133Y mutation inactivated the canonical Notch1 signaling. We identified an oncogenic phenotype of this mutation by promoting cell proliferation, invasion and by inducing EMT in OSCC cell lines. We found that the Notch1C1133Y mutation exhibited a decreased S1-cleavage due to the impaired transport of Notch1 protein from the endoplasmic reticulum (ER) to the Golgi complex, which was consistent with the observation of the failure of the Notch1C1133Y mutated receptor to present at the cell surface. Importantly, the mutated Notch1 activated the EGFR-PI3K/AKT signaling pathway, which has been confirmed as an overwhelming modulator in OSCC. CONCLUSIONS: Taken together, our findings revealed for the first time a novel Notch1 mutation that enhances proliferation and invasion in OSCC cell lines. The Notch1 C1133Y mutation impairs the processing of notch1 protein and the critical links between the mutated Notch1 and the activated EGFR-PI3K/AKT signaling pathway.

MiR-876-5p modulates head and neck squamous cell carcinoma metastasis and invasion by targeting vimentin.

BACKGROUND: Local or distant metastasis remains the main course of death in head and neck squamous cell carcinoma (HNSCC) patients. MicroRNAs (miRNAs) have been implicated in metastasis of HNSCC, but the mechanisms of their action are mainly undocumented. Through public head and neck cancer miRNA expression datasets, we found that miR-876-5p was a novel potential tumor suppressor targeting HNSCC metastasis. METHODS: Clinical significance and mechanism of miR-876-5P was systematically analyzed in HNSCC. Quantitative RT-PCR was used to evaluate miR-876-5p levels in HNSCC cell lines and in 20 pairs of HNSCC with associated regional nodal metastases and HNSCC without metastatic primary tumors. Scratch and invasion assays were evaluated to determine the role of miR-876-5p in the regulation of HNSCC cell migration and invasion, respectively. Western blotting was used to investigate the mechanism by which miR-876-5p suppresses HNSCC cell invasion and migration. Luciferase assays were performed to assess miR-876-5p binding to the vimentin gene. The animal model was used to support the in vitro experimental findings. RESULTS: MiR-876-5p mimics inhibited HNSCC cell migration and invasion. Vimentin protein and mRNA levels were decreased in the miR-876-5p mimics group but increased in the miR-876-5p inhibitors group, which demonstrated that miR-876-5p inhibits vimentin expression in HNSCC cells. By directly targeting the vimentin 3'-UTR, we used dual-luciferase reporter assays to verify that vimentin is a functional downstream target of miR-876-5p. Importantly, increased vimentin expression promoted cell migration and invasion, and co-transfection with miR-876-5p mimics and vimentin restored cell aggressiveness to the original level. Moreover, miR-876-5p overexpression significantly downregulated vimentin expression level and inhibited the distal metastasis of HNSCC cells in vivo. CONCLUSIONS: miR-876-5p, which functions as a tumor suppressor in HNSCC, inhibits metastasis by targeting vimentin and provides a novel therapeutic target for HNSCC treatment.

Serum bilirubin level predicts postoperative overall survival in oral squamous cell carcinoma.

BACKGROUND: Aberrant level of serum bilirubin, marker of hepatobiliary and hematological disorders, was associated with patient prognosis in several human malignancies. In this study, we aim to evaluate the predictive value of serum bilirubin for clinicopathologic characteristics and survival of patients with oral squamous cell carcinoma (OSCC). METHODS: This study retrospectively reviewed 129 patients with OSCC and 129 normal controls matched for age and sex. The association between levels of preoperative direct bilirubin (DBIL), indirect bilirubin (IBIL), total bilirubin (TBIL), and clinical variables was analyzed. A proportional hazards regression model was used to find out the independent predictors of survival. RESULTS: Significantly lower TBIL (P = .009) and IBIL (P < .001) were found in OSCC patients compared with normal controls. DBIL (P = .011) and lymph-node metastasis (P = .031) were found to be independent prognostic factors. Patients with higher DBIL (≥4.0 µmol/L) had longer overall survival than those with lower DBIL (P = .002). Patients with both lymph-node metastasis and lower DBIL showed the shortest overall survival (P = .001). CONCLUSIONS: Lower DBIL was associated with a poorer prognosis and may be regarded as an independent prognostic marker for patients with OSCC.

Immediate implant placement and complete mouth rehabilitation with CAD-CAM titanium frameworks and cemented crowns for a patient with severe periodontal disease: A clinical report.

The technique of immediate implantation has been widely used to reduce treatment time and bone loss after extraction. However, immediate implant placement in infected extraction sockets is generally contraindicated. This clinical report describes a treatment protocol for immediate implantation after the extraction of teeth with generalized chronic periodontitis. The technique used for the oral rehabilitation used computer-assisted design and computer-assisted manufacturing (CAD-CAM) titanium frameworks and cemented zirconia crowns. The titanium frameworks overcame suboptimal implant position and the cemented crowns provided excellent function and esthetics despite the locations of screw-access openings. No clinical complications occurred during a 13-month follow-up.

Alteration of serum lipid profile and its prognostic value in head and neck squamous cell carcinoma.

BACKGROUND: Several serum lipid components have been implicated in the development of cancer. However, the prognostic significance of serum lipid components in head and neck squamous cell carcinoma is unknown. Here, we investigated the predictive value of serum lipid profile at diagnosis and in the overall survival of the patients. METHODS: The study population consists of 136 pathologically confirmed head and neck squamous cell carcinoma cases diagnosed between years 2009 and 2014 at a tertiary medical center. Levels of preoperative serum lipid component's total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, apolipoprotein A, apolipoprotein B, and lipoprotein (a) were compared between patients and normal controls matched for age and gender. Serum lipid profiles and their association with clinical parameters were analyzed. The effects of the serum lipid components on survival were examined using the proportional hazards regression model to estimate hazard ratio. RESULTS: Significant lower levels of cholesterol, low-density lipoprotein, apolipoprotein A, and apolipoprotein B were found in patients with oral cancer (P < 0.0001). However, a significantly higher level of lipoprotein (a) was found in the cancer group (P < 0.0001). Patients with higher lipoprotein (a) had significantly shorter overall survival than those with lower lipoprotein (a) (P = 0.0042). Multivariate analysis showed that both higher lipoprotein (a) and lymph node metastasis are independent prognostic factors in the patient population (P < 0.01). CONCLUSION: A higher lipoprotein (a) was associated with poorer prognosis and might be a novel marker in patients with head and neck squamous cell carcinoma.

Exacerbated cardiac fibrosis induced by ß-adrenergic activation in old mice due to decreased AMPK activity.

Senescent hearts exhibit defective responses to ß-adrenergic receptor (ß-AR) over-activation upon stress, leading to more severe pathological cardiac remodelling. However, the underlying mechanisms remain unclear. Here, we investigated the role of adenosine monophosphate-activated protein kinase (AMPK) in protecting against ageing-associated cardiac remodelling in mice upon ß-AR over-activation. 10-week-old (young) and 18-month-old (old) mice were subcutaneously injected with the ß-AR agonist isoproterenol (ISO; 5 mg/kg). More extensive cardiac fibrosis was found in old mice upon ISO exposure than in young mice. Meanwhile, ISO treatment decreased AMPK activity and increased ß-arrestin 1, but not ß-arrestin 2, expression, and the effects of ISO on AMPK and ß-arrestin 1 were greater in old mice than in young mice. Similarly, young AMPKα2-knockout (KO) mice showed more extensive cardiac fibrosis upon ISO exposure than that was observed in age-matched wild-type (WT) littermates. The extent of cardiac fibrosis in WT old mice was similar to that in young KO mice. Additionally, AMPK activities were decreased and ß-arrestin 1 expression increased in KO mice. In contrast, the AMPK activator metformin decreased ß-arrestin 1 expression and attenuated cardiac fibrosis in both young and old mice upon ISO exposure. In conclusion, more severe cardiac fibrosis is induced by ISO in old mice than in young mice. A decrease in AMPK activity, which further increases ß-arrestin 1 expression, is the central mechanism underlying the ageing-related cardiac fibrosis induced by ISO. The AMPK activator metformin is a promising therapeutic agent for treating ageing-related cardiac remodelling upon ß-AR over-activation.

Clinicopathological Characteristics and Outcome Predictors in Squamous Cell Carcinoma of the Maxillary Gingiva and Hard Palate.

PURPOSE: Squamous cell carcinoma (SCC) located in the maxillary gingiva and hard palate is relatively rare. There are few published guidelines for the treatment of SCC of the maxilla. The aim of the present study was to characterize the clinicopathologic features of SCC of the maxillary gingiva and hard palate and determine factors that predict outcome and lead to a strategic treatment plan. MATERIALS AND METHODS: A retrospective cohort study of patients with SCC of the maxillary gingiva and hard palate was conducted from 2003 to 2012 at the Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University. Clinicopathologic characteristics, treatments, outcome predictors, and 3- and 5-year overall survival rates were analyzed. The Kaplan-Meier method was used to evaluate 3- and 5-year overall survival rates. Univariate and multivariate Cox regression analyses were used to identify predictors of survival. A P value less than .05 was considered statistically significant. RESULTS: The 3- and 5-year survival rates of the 62 participants were 66.6 and 57.3%, respectively. Univariate analyses showed statistically significant (P < .05) associations between patient survival rate and tumor differentiation grade, T classification, marginal status, cervical lymphatics, and local recurrence. Occult lymph node metastases of maxillary SCC in tumor stages T2 to T4 occurred in 20 to 40% of patients. Patients who presented with lesions located after the first premolar plane area and received postoperative radiotherapy had a better prognosis. CONCLUSION: Elective neck dissection is recommended for management of T2 to T4 SCCs in the maxillary gingiva and hard palate. Postoperative radiotherapy can improve the prognosis and decrease the recurrence of SCC after the first premolar plane area.

Extended Free Forearm Flap for Treatment of Temporomandibular Joint Pseudoankylosis.

Pseudoankylosis of temporomandibular joint (TMJ) is characterized by limited mouth opening and impaired mandibular mobility induced by pathologic factors outside the joint itself, usually leading to compromised speech, swallowing, and breath functions. Multiple surgical approaches or reconstructive procedures have been proposed to resolve the joint pseudoankylosis and restore the mandibular movement for these affected patients. Free forearm flap has been widely used in reconstruction for various congenital or acquired defects or deformities; however, this flap has been rarely employed for TMJ pseudoankylosis in the literature. Here, the authors reported that noma-induced TMJ pseudoankylosis was diagnosed and successfully treated by extended free forearm flap with length over 10 cm in a Chinese female patient.

Medial sural artery perforator flap for postsurgical reconstruction of head and neck cancer.

BACKGROUND: This article aims to describe the application of medial sural artery perforator flaps (MSAPs) in reconstruction of defects following ablation of head and neck cancer. METHODS: The study included 24 patients (10 males and 14 females). A total of 24 MSAPs were harvested to reconstruct defects caused by the dissection of malignant tumors of the oral and maxillofacial regions. Overall, 20 radial forearm free flaps (RFFs) and 16 anterior lateral thigh perforator flaps (ALTPs) were included in the donor site cosmetic assessments. Visual analog scale (VAS) score was used to assess postoperative oral function and cosmetic results. RESULTS: A total of 22 (92%) flaps healed without venous insufficiency. The external diameter of the medial sural artery for anastomosis was 2.2 mm (range, 1.3-2.5 mm), and the external diameter of the venae comitantes was 2.6 mm (range, 1.5-3.5 mm). Esthetic satisfaction with the primary site had a VAS score of 6.38 ± 1.89, while the donor site had a score of 7.34 ± 1.28. Use of MSAP and ALTP showed significantly higher esthetic satisfaction at the donor site than with RFF (p < 0.001 and p < 0.05, respectively). CONCLUSION: MSAPs show a strong advantage for donor site esthetic outcome and can be a good choice for the repair of defects of the maxillofacial area after cancer ablation.

α-Smooth muscle actin-positive myofibroblasts, in association with epithelial-mesenchymal transition and lymphogenesis, is a critical prognostic parameter in patients with oral tongue squamous cell carcinoma.

BACKGROUND: α-Smooth muscle actin (α-SMA)-positive myofibroblasts play a pivotal role in progression and metastasis of solid carcinomas. Epithelial-mesenchymal transition (EMT) of cancer cells and lymphogenesis of tumor microenvironment are the important events in tumor metastasis. This study aimed to investigate the relationship between the expression of myofibroblasts marker, α-SMA, and clinicopathological features, EMT, lymphogenesis, and prognostic status in oral tongue squamous cell carcinoma (OTSCC). METHODS: Immunohistochemisty was used to detect α-SMA expression in 50 OTSCCs. EMT and lymphogenesis were also identified by immunostaining with N-cadherin, vimentin, and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1). RESULTS: There was a significant correlation respectively between the α-SMA (P = 0.002), vimentin (P < 0.001), N-cadherin (P = 0.025) expression and cervical lymph node metastasis of OTSCC. Carcinomas with α-SMA (P = 0.001), vimentin (P = 0.003), and N-cadherin (P = 0.012) expression were more advanced in terms of tumor-node-metastases status. Univariate analysis showed that pathologic node status (P < 0.001), α-SMA (P = 0.001), and vimentin expression (P = 0.044) was significantly associated with overall survival time, but multivariate analysis just showed the α-SMA expression (P = 0.008) and pathologic node status (P = 0.003) was independently predictive of prognosis. Furthermore, statistical analysis showed significant correlation between α-SMA expression and vimentin (P = 0.037), N-cadherin (P = 0.019), or LYVE-1 positive vessel count (P = 0.041). CONCLUSION: Our results indicate that α-SMA-positive myofibroblasts have important impacts on cancer progression, metastasis, and survival prognosis of patients with OTSCC. The functions of α-SMA-positive myofibroblasts in OTSCC may be associated with promoting EMT of tumor cells and lymphogenesis of metastasis microenvironment.

The axis inhibition protein 2 polymorphisms and non-syndromic orofacial clefts susceptibility in a Chinese Han population.

BACKGROUND: The axis inhibition protein 2 (AXIN2) is an important regulator of ß-catenin degradation in the Wnt pathway, which plays a key role in craniofacial morphogenesis. The goal of this study was to investigate the potential relationship between AXIN2 polymorphisms and the risks of non-syndromic orofacial clefts (NSOC) in a Chinese Han population. METHODS: Four polymorphisms of AXIN2 (rs2240307, rs11867417, rs2240308, and rs7591) were selected to perform a case-control study with 599 NSOC cases and 602 healthy individuals from a Chinese Han population. The single nucleotide polymorphisms (SNPs) were genotyped on basis of double ligation and multiplex fluorescence PCR. RESULTS: Weak associations were found between these four SNPs and the risk of NSOC. Further stratified analysis showed that the overall genotype frequencies of rs2240307 were different between the cleft palate only (CPO) group and the control group (P = 0.048), and GG genotype markedly contributed to the susceptibility to CPO (OR = 3.22, 95% CI = 1.13-9.18). The similar effect was also observed on GA/AA genotype compared with GG homozygote (OR = 0.30, 95% CI = 0.11-0.84). The results of LD analysis between each pair of SNPs revealed that two SNPs (rs11867417 and rs7591) were in a LD block (r(2) > 0.8). But no statistically significant was found between cases and controls from haplotype analysis in these two loci. CONCLUSIONS: The borderline results gave us a hint that rs2240307 contributed to the susceptibility to CPO in a Chinese Han population, which was conductive to improving our awareness of the causes of NSOC.

Brush biopsy with DNA-image cytometry: a useful and noninvasive method for monitoring malignant transformation of potentially malignant oral disorders.

Oral and pharyngeal cancer is the sixth most common cancer worldwide, the 5-year survival rate has not yet increased. A key factor in rates not having improved is the lack of early detection. This study was undertaken to estimate the diagnostic accuracy of brush biopsy with DNA-image cytometry (a noninvasive method) for potentially malignant oral disorders compared with tissue biopsy pathology in China. Exfoliative cells were obtained using a cytobrush cell collector from oral mucosa of 52 subjects, followed by scalpel biopsy from the same region. Nuclear DNA contents (ploidy) were measured after Feulgen restaining, using an automated DNA image cytometer. Exfoliative cytology with DNA-image cytometry and histopathological diagnosis were performed separately at different institutions. Histological investigation was considered the gold standard. We reported that the sensitivity of DNA aneuploidy for the detection of cancer cells in potentially malignant oral disorders was 86.36 %, its specificity was 90.00 %, its positive predictive value was 86.36 %, and its negative predictive value was 90.00 %. Brush biopsy with DNA-image cytometry is a useful method for monitoring potentially malignant oral disorders.

Reconstruction of palatomaxillary defects following cancer ablation with temporalis muscle flap in medically compromised patients: a 15-year single institutional experience.

OBJECTIVES: Successful reconstruction of palatomaxillary defects following cancer ablation represents a formidable challenge for surgeons to achieve consistently favorable outcomes. The purpose of this article is to present our experience in oncologic palatomaxillary repair with temporalis muscle flap (TMF) for medically compromised patients who are not ideal candidates for microvascular reconstruction at a Chinese tertiary referral hospital over a 15-year period (1998-2012). METHOD: A retrospective chart review was performed to identify patients with compromised medical conditions who underwent oncologic palatomaxillary reconstruction using TMF. Patients' demographics, clinicopathological variables, and surgical techniques were presented. Postoperative functional and aesthetic outcomes were assessed by measurements and patients self-evaluations. RESULTS: Sixty-nine TMFs were successfully harvested and used for immediate oncologic palatomaxillary reconstruction in 67 patients (31 males and 36 females, mean age 60.4 years) with diverse primary malignancies. These patients' co-morbidities included systemic diseases, preoperative chemotherapy/radiotherapy, and elder over 65 years which precluded the ideal utility of free flaps. Fifty-one patients remained alive without disease, while nine had recurrences/metastases and seven died during the follow-up (0.5-10.4 years, mean 3.7 years). All flaps survived with only partial necroses in four cases. Complications and donor-site morbidities were minimal with five transient facial paralysis and four mild diplopia and enophthalmos. Unrestricted diet and mouth opening, intelligible speech, and satisfactory temporal aesthetics were obtained in most patients. CONCLUSION: The TMF is a reliable, versatile, and alternative option for oncologic palatomaxillary reconstruction with satisfactory functional and aesthetic outcomes and minimal complications, especially when appropriately selected for those medically compromised patients.