Oral Oncology - Articles in Press

Resident and bone marrow-derived mesenchymal stem cells in head and neck squamous cell carcinoma - Corrected Proof

2010-03-11

Summary: Head and neck squamous cell carcinoma (HNSCC) is a major healthcare problem worldwide affecting more than half a million patients each year. Despite considerable advances in the treatment of HNSCC, a high rate of recurrences aggravates the clinical situation and disease outcomes have only modestly improved. Recent insights show that cancer is not only a disease of the transformed epithelium but is also influenced and dependent on its stromal environment. In this review we suggest that resident and bone marrow (BM)-derived mesenchymal stem cells (MSCs) are precursors of the stroma associated with HNSCC and contribute to blood- and lymph angiogenesis, modulate the immune system and produce tumor-associated myofibroblasts. In addition, the impact of radiation therapy on the stromal reaction in HNSCC is discussed. Understanding the mechanisms of how MSCs promote invasive growth and metastasis in HNSCC and respond to cancer management strategies is of profound medical importance and will help us to design improved therapeutic protocols.

The implication of osteopontin (OPN) expression and genetic polymorphisms of OPN promoter in oral carcinogenesis - Corrected Proof

2010-03-11

Summary: Osteopontin (OPN) is an extracellular matrix protein in hard tissues. The polymorphism in promoter region of OPN gene correlates to different gene expression and might implicate potential roles in tumor progression and metastasis. Immunohistochemistry (IHC) was utilized to detect the OPN expression in 58 oral squamous cell carcinoma (OSCC) tissues and adjacent normal oral mucosa. The differential OPN expression was further analyzed in relation to clinico-pathological features. Genomic DNA was obtained from isolated leukocytes of blood samples of OSCC patients (n=100), and healthy individuals (n=97) from Taiwan. The OPN gene polymorphism was analyzed by direct sequencing. Our result showed OPN expression was significantly higher in OSCC tissues than in the paired adjacent normal tissues (p<0.01). The expression of OPN was significantly associated with nodal metastasis and the more advanced clinical stage (p<0.05). More prevalent −156 insGG/insGG genotype and −443 T/T genotype was found in OSCC patients (p<0.05). A significant difference in −443T/−156GG/−66T and −443C/−156G/−66T haplotypes between OSCC and controls (p<0.05) was also noted. The OPN expression in tumor tissues significantly correlated with −156 insGG/insGG and −156 G/G+insGG/G genotypes (p<0.05). The conclusion is tissue OPN expression correlates to OSCC progression. −156 insGG/insGG genotype is associated with OSCC susceptibility and higher OPN expression.

Expression of c-kit and Slug correlates with invasion and metastasis of salivary adenoid cystic carcinoma - Corrected Proof

Yaling Tang, Xinhua Liang, Min Zheng, Zhiyu Zhu, Guiquan Zhu, Jing Yang, Yu Chen — 2010-03-11

Summary: The overexpression of c-kit seems to be frequent and specific in salivary adenoid cystic carcinoma (ACC), however, there is little information on correlation between c-kit expression and the invasion and metastasis. Recently, the data showed that Slug, a transcription factor of epithelial–mesenchymal transitions (EMT), is a molecular target that contributes to the biological specificity of c-kit signaling pathway. In this study, the expression of c-kit and Slug was evaluated in two ACC cell lines and 121 patients with ACC. The results of real-time RT-PCR and Western blot showed that ACC-2 and ACC-M cell lines expressed c-kit and Slug mRNA and protein. The immunohistochemical assay in patients demonstrated that positive expression of c-kit and Slug was observed in 108/121 (89.26%) and 87/121 (71.90%) of cases, respectively, and that c-kit and Slug expression was significantly associated with tumor site, TNM stage, histological pattern, perineural invasion, local regional recurrence and distant metastasis of patients with ACC (P<0.05). Furthermore, there was a significant association between the positive expression of c-kit and that of Slug (P=0.046). These findings indicated that c-kit/Slug pathway might participate in the invasion and metastasis of salivary ACC.

MicroRNAs contribute to the chemoresistance of cisplatin in tongue squamous cell carcinoma lines - Corrected Proof

Zhi-wei Yu, Lai-ping Zhong, Tong Ji, Ping Zhang, Wan-tao Chen, Chen-ping Zhang — 2010-03-11

Summary: MicroRNAs (miRNAs) are small non-coding RNAs that function as negative regulators of gene expression. They are strongly implicated in human cancers, including oral squamous cell carcinoma (OSCC). Evidence for the involvement of miRNAs as important regulators of chemosensitivity and chemoresistance in OSCC is not well understood. In this study, miRNA microarray was firstly used to compare the differential miRNAs levels between the cisplatin-sensitive tongue squamous cell carcinoma line (Tca8113) and its cisplatin-resistant subline (Tca/cisplatin). Three miRNAs of miR-21, -214, and -23a were validated by miRNAs real-time PCR, and intervened by anti-miRNA oligonucleotides (miR-214 and -23a) and pre-miRNA plasmid transfection (miR-21). Further relationship between miR-23a and DNA topoisomerase II beta (TOP2B) on the chemoresistance against cisplatin was studied. There were 19 out of 480 differential miRNAs between the Tca8113 and Tca/cisplatin cells. miR-214 and -23a were found increased as with chemoresistance against cisplatin in the Tca/cisplatin cells while miR-21 was found decreased as with chemosensitivity for cisplatin in the Tca/cisplatin cells. Intervention of these three miRNAs could decrease the chemoresistance against cisplatin in Tca/cisplatin cells. Transfection of anti-miR-23a into the Tca/cisplatin cells could increase the TOP2B protein expression. Our results suggest the existence of differential miRNAs with chemosensitivity and chemoresistance between the cisplatin-sensitive and resistant tongue squamous cell carcinoma lines. miR-21 serves as a chemosensitive miRNA, while miR-214 and -23a serve as chemoresistant miRNAs in the tongue squamous cell carcinoma lines. miR-23a is an up-stream regulator of TOP2B to realize the chemoresistance of cisplatin.

Validation of the Sydney Swallow Questionnaire (SSQ) in a cohort of head and neck cancer patients - Corrected Proof

2010-03-11

Summary: Impairment of swallowing function is a common multidimensional symptom complex seen in 50–75% of head and neck cancer (HNC) survivors. Although there are a number of validated swallowing-specific questionnaires, much of their focus is on the evaluation of swallowing-related quality of life (QOL) rather than swallowing as a specific function. The aim of this study was to validate the Sydney Swallow Questionnaire (SSQ) as a swallowing-specific instrument in HNC patients.Fifty-four consecutive patients in follow-up for oral and oropharyngeal cancer completed the SSQ and MD Anderson Dysphagia Inventory (MDADI). Thirty-one patients completed both questionnaires again four weeks later to address test–retest reliability. Internal consistency and test–retest reliability was assessed using Cronbach’s α and Spearman’s correlation coefficient, respectively. Construct validity (including group validity) and criterion validity were determined using Spearman’s correlation coefficient and Mann–Whitney U-test.Internal consistency, test–retest reliability, construct validity, group validity and criterion validity of the SSQ was found to be significant (P<0.01).We were able to demonstrate the reliability and validity of the SSQ in HNC patients. The SSQ is a precise, reliable and valid tool for assessing swallow in this patient group.

Diallyl sulfide induces growth inhibition and apoptosis of anaplastic thyroid cancer cells by mitochondrial signaling pathway - Corrected Proof

Hyang Ae Shin, Yun Yi Cha, Mun Su Park, Jae Myeong Kim, Young Chang Lim — 2010-03-11

Summary: Anaplastic thyroid carcinoma (ATC) is one of the most lethal solid tumors arising thyroid gland with dismal prognosis. One of the constituents of garlic, diallyl sulfide (DAS) was shown to inhibit chemically induced carcinogenesis in many animal models. This study examined whether DAS could induce growth inhibition and apoptosis in ATC cells. In MTT assay, DAS treatment inhibited the proliferation of ARO cells in a dose-dependent manner. Flow cytometric analysis showed that DAS treatment increased the accumulation of sub-G1 DNA and concomitant accumulation of cells in the G2/M phase in a dose-dependent manner. In addition, DAS-induced apoptosis was associated with a decrease in the level of Bcl-2 expression and an increase in the level of Bax expression, and cytochrome c was remarkably released from mitochondrial into the cytosol by DAS. Furthermore, caspase-9 and caspase-3 were activated by DAS, and DAS cleaved PARP. Taken together, DAS decreased cell proliferation and induced apoptosis via mitochondrial signaling pathway in ATC cells.

Potential role of HDAC inhibitors in cancer therapy: Insights into oral squamous cell carcinoma - Corrected Proof

A. Iglesias-Linares, R.M. Yañez-Vico, M.A. González-Moles — 2010-03-08

Summary: Histone deacetylases (HDACs) are enzymes that are involved in the remodeling of chromatin and play a key role in the epigenetic regulation of gene expression. In addition, the activity of non-histone proteins can be regulated through HDAC-mediated hypoacetylation. In recent years, inhibition of HDACs has emerged as a potential strategy to reverse aberrant epigenetic changes associated with cancer, and several classes of HDAC inhibitors have been found to have potent and specific anti-cancer activities in preclinical studies. Many researchers have highlighted the need to determine specific HDAC isotypes related to different tumor types in order to develop selective drugs for specific isoforms and avoid side effects. We summarize recent advances in the understanding of the molecular events that underlie the epigenetic changes in different tissue carcinomas, focusing on oral squamous carcinoma. The role of epigenetics in oral squamous cancer remains poorly understood, and further descriptive studies of specific HDAC member alterations are required to form the basis for future clinical trials.

Primary tumors of the submandibular glands: A retrospective study based on 41 cases - Corrected Proof

Panagiotis Ziglinas, Andreas Arnold, Marlene Arnold, Peter Zbären — 2010-03-02

Summary: We report our experience on the diagnostic approach, treatment, and follow-up of primary submandibular gland tumors. Retrospective review. Tertiary referral center. Forty-one adult patients, 22 male and 19 female, with primary submandibular gland tumors, 20 benign and 21 malignant. Age, gender, clinical findings, cyto- and histopathology, treatment and outcome were analyzed. Most tumors presented as a painless submandibular mass. Thirty three patients underwent a fine needle aspiration, the sensitivity, specificity and accuracy of which – in detecting malignant tumors – were 79%, 100% and 88%, respectively. Preoperative radiological imaging was performed in 30 cases. Patients with benign tumors were treated with surgery. Most malignant tumors were treated with a combined modality, including neck dissection and radiation therapy. Five patients developed a postoperative complication. Recurrent disease was encountered in 5 malignant tumors. The 2, 5 and 10year disease-specific survival of patients with malignancy were 84%, 75% and 41%, respectively. The preoperative assessment of the nature of submandibular gland tumors remains challenging. Aggressive treatment of patients with malignant disease may help to avoid poor prognosis.

Characterization and management of the keratocystic odontogenic tumor in relation to its histopathological and biological features - Corrected Proof

Rui Amaral Mendes, João F.C. Carvalho, Isaac van der Waal — 2010-03-02

Summary: Keratocystic odontogenic tumor (KCOT), formerly referred to as odontogenic keratocyst, is a benign neoplasm of odontogenic origin which may present an aggressive and infiltrative behavior leading to high recurrence rates. A review of the various treatment modalities, ranging from simple enucleation to radical surgery is portrayed in relation to clinical, radiological, histopathological and molecular features.Although prognostic factors based on clinico-pathologic and immunohistochemical findings for determining the potential for recurrence of KCOT still remains unclear, its use for determining the potential for recurrence of KCOT after surgical treatment may become important to successfully manage this neoplasm’s aggressive behavior.The key element for future management of KCOTs will probably be based on thorough knowledge of the biological basis of this tumor, thereby enabling a more tailored treatment approach.

Comprehensive review of small bowel metastasis from head and neck squamous cell carcinoma - Corrected Proof

2010-03-02

Summary: Secondary tumours of small intestine account for 10% of all small bowel cancers. The most common sites of primary tumour metastasizing to small bowel are uterus, cervix, colon, lung, breast and melanoma. The majority of these metastatic tumours come from adenocarcinoma primaries; squamous cell carcinoma constitutes a very small proportion of all metastatic small intestinal lesions. Metastasis to small bowel by head and neck squamous cell carcinoma is extremely rare and carries an unfavourable prognosis. Owing to the limited number of published studies, its characteristic features, clinical presentation and outcomes are poorly described. This work aims at specifying these characteristics by reviewing, compiling, analysing and reporting all published cases in the published literature on small bowel metastasis secondary to head and neck squamous cell carcinoma. To the best of our knowledge, this is the first comprehensive review article on the small intestinal metastasis from head and neck squamous cell carcinoma.

Betel-quid chewing with or without tobacco is a major risk factor for oral potentially malignant disorders in Sri Lanka: A case-control study - Corrected Proof

2010-03-02

Summary: We investigated the prevalence of, and risk factors for, oral potentially malignant disorders (OPMDs) in rural Sri Lanka. A cross-sectional community-based study was conducted by interview and oral examination of 1029 subjects aged over 30years. A community-based nested case-control study then took those with OPMDs as ‘cases’, “controls” being those with no oral abnormalities at time of initial screening. The prevalence of OPMD was 11.3% (95% CI: 9.4–13.2), after weighting for place of residence and gender. Risk factors were betel-quid (BQ) chewing daily [OR=10.6 (95% CI: 3.6–31.0)] and alcohol drinking daily or weekly [OR=3.55 (1.6–8.0)]. A significant dose–response relationship existed for BQ chewing. Smoking did not emerge when adjusted for covariates. A synergistic effect of chewing and alcohol consumption existed. The attributable risk (AR) of daily BQ chewing was 90.6%, the population AR 84%. This study demonstrates high prevalence of OPMD, betel-quid chewing with or without tobacco being the major risk factor.

Molecular analysis of surgical margins in head and neck cancer: More than a marginal issue - Corrected Proof

2010-03-02

Summary: The relatively modest survival of patients surgically treated for advanced HNSCC can partly be explained by the development of local relapse. It is important that surgeons are able to predict which patients are at high risk to develop local relapse, since clinical management can be tailored. Local relapse after resection of a primary HNSCC is easily explained, when tumour is detected in the surgical margins and thus residual tumour is likely to remain in the patient, but the pathobiology is more complex in cases where the margins are histologically tumour-free. Molecular studies indicate that there are two different mechanisms responsible in these cases. First, small clusters of residual tumour cells that are undetectable on routine histopathological examination (known as minimal residual cancer: MRC) proliferate and this forms the basis of recurring cancer. A second cause of relapse is a remaining field of preneoplastic cells that is struck by additional genetic hits leading to invasive cancer. It is likely that within this field, that can be over 7cm in diameter, the primary carcinoma has also emerged. Despite careful histopathological examination of the surgical margins of the primary carcinoma, it is at present not reliably possible to predict which patient will develop local relapse. Herein we focus on new developments regarding the analysis of margins, causes of local relapse, and how novel molecular techniques can be of help in a more accurate risk assessment. Critical analysis of the studies that have been published thus far shows that there is a list of promising markers, based on protein expression (immuno-histochemistry) and nucleic acid analysis. Further studies should be focused on validation and assessment of the clinical utility of these markers. Margin analysis should reveal whether one is dealing with residual cancer cells that might be treated by post-operative radiotherapy or with preneoplastic fields that remained behind. For this latter entity, there is no intervention available at present, except for a more intensive surveillance.

Narrow band imaging and high definition television in evaluation of oral and oropharyngeal squamous cell cancer: A prospective study - Corrected Proof

2010-03-02

Summary: Narrow band imaging (NBI) is an optical technique in which filtered light enhances superficial neoplasms based on their neoangiogenic pattern. The accuracy of NBI can be augmented by combining it with high definition television (HDTV). The aim of this study was to prospectively assess the diagnostic value of NBI in combination with HDTV in evaluation of oral (O) and oropharyngeal (OP) squamous cell carcinoma (SCC). Between April 2007 and December 2009, we analyzed 96 patients who were divided into 2 groups: Group A included 35 patients previously biopsied and diagnosed with OSCC or OPSCC and subjected to pre- and intraoperative HDTV white light (WL) and HDTV NBI endoscopy; Group B included 61 subjects already treated for OSCC or OPSCC and followed-up with HDTV WL and HDTV NBI. Fourteen of 35 (40%) patients in Group A showed adjunctive findings with NBI compared to standard WL. All of these findings were histologically confirmed. Twelve of 61 (20%) patients in Group B showed positive NBI findings, which were all confirmed by histology. The sensitivity, specificity, positive, negative predictive values, and accuracy for HDTV WL were 51%, 100%, 100%, 87%, and 68%, respectively, whilst for HDTV NBI were 96%, 100%, 100%, 93%, and 97%, respectively. Overall, 26 of 96 (27%) patients had a diagnostic advantage in applying NBI and HDTV: 6 patients received a diagnosis of recurrence and 1 of persistence after previous treatments; 5 showed a metachronous tumour; in 4 a synchronous tumour was diagnosed; 9 lesions were upstaged; in 1 patient previously diagnosed with an unknown primary by fine needle aspiration cytology on the neck, an anterior tonsillar pillar cancer was identified.

Epidermal growth factor receptor (EGFR)-inhibitors, rashes, and survival: Is doxycycline the missing link? - Corrected Proof

David Palma — 2010-03-02

In a recent article in Oral Oncology, Shen and colleagues assessed the effect of doxycycline on the growth of oral squamous cell carcinoma (SCC). Doxycycline is an antibiotic with inhibitory effects on matrix metalloproteinases (MMPs), enzymes that digest the extracellular matrix and basement membrane and are involved in angiogenesis, invasion and metastasis. The authors found that doxycycline inhibits SCC growth in vitro and in mice, and these effects are correlated with inhibition of MMPs. Similar effects of doxycycline have been demonstrated in other cell lines, including colorectal cancer cells.

Effectiveness of image-guided radiotherapy for laryngeal sparing in head and neck cancer - Corrected Proof

2010-02-26

Summary: We would like to compare the effectiveness of image-guided (IGRT) and intensity-modulated (IMRT) radiotherapy to spare the larynx in head and neck cancer patients. A retrospective review of 48 patients undergoing radiation for non-laryngeal and non-hypopharyngeal head and neck cancers. Mean laryngeal and hypopharyngeal dose was compared between 11 patients treated with IMRT and 37 patients treated with IGRT. Mean laryngeal dose was, respectively, 41.2Gy and 22.8Gy for the IMRT and IGRT technique (p<0.001). The radiation dose to the middle and inferior pharyngeal muscles was also significantly reduced with the IGRT technique. Mean pharyngeal dose was, respectively, 52Gy and 26Gy for the IMRT and IGRT technique (p=0.0001). Laryngeal sparing IGRT technique for head and neck cancer minimizes radiotherapy dose to the larynx and pharynx without sacrificing target coverage, even in the presence of neck lymph nodes.

Outcomes of oral cavity squamous cell carcinoma in pediatric patients - Corrected Proof

Luc G.T. Morris, Ian Ganly — 2010-02-26

Summary: Oral cavity squamous cell carcinoma (OCSCC) is uncommon in young patients and rare in the pediatric population. OCSCC is believed to behave aggressively in this age group, but the existing literature is limited to case reports. The objective of this study was to compare survival outcomes in pediatric and adult patients with oral cavity squamous cell carcinoma.We performed a population-based study of 54 pediatric (age⩽20) and 22,162 adult cases of OCSCC, recorded in the SEER cancer registry. Overall survival (OS) and disease-specific survival (DSS) were analyzed using the Kaplan–Meier method. Cox multivariable regression was used to control for covariates including gender, stage, histologic grade and treatment modality.Pediatric patients with OCSCC experienced significantly better 5year DSS than adult patients (75.3% vs. 63.5%, p=0.02). Pediatric patients were also more likely to be female (37.0% vs. 31.7%, p=0.04) and to receive surgery (87.0% vs. 68.6%, p<0.001). When these factors, as well as non-significant differences in rates of metastases and histologic grade were controlled for on multivariable analysis, the pediatric and adult groups experienced equivalent DSS (p=0.64).Pediatric patients with OCSCC experience better survival than adult patients. When differences in patient, tumor and treatment-related characteristics are adjusted for, the two groups experience equivalent survival.

Characterization of different tissue changes in normal, betel chewers, potentially malignant lesions, conditions and oral squamous cell carcinoma using reflectance confocal microscopy: Correlation with routine histopathology - Corrected Proof

2010-02-08

Summary: The goal of this study was to characterize the features of normal mucosa, mucosa in betel chewers and smokers, potentially malignant lesions and squamous cell carcinoma of oral mucosa using reflectance confocal microscopy.Oral cavity biopsies were acquired from 25 patients from College of Dental Surgery, Saveetha University who underwent screening for suspected lesions of Oral precancer and Oral cancer along with normal patients who underwent impaction. Biopsies were acquired from the clinically suspicious area and immediately placed in Dulbecco modified eagles growth medium (DMEM). Reflectance confocal images were obtained at multiple image plane depths from biopsies within 6h of excision. After imaging, biopsies were fixed in 10% formalin and submitted for routine histopathological examination by an experienced oral and maxillofacial pathologist. Reflectance confocal images were compared with histological images from the same sample to determine the tissue features which contribute to early cellular changes, image contrast and early diagnosis.The confocal images were obtained to a depth of up to 150microns on intact biopsy specimens and subsequent 3-dimensional images, keratin thickness measurements, cell measurements, cell density analysis and graphical representations were performed using Leica image analysis software. In normal mucosa keratin deposition were seen as alternating dark and bright stacks and in different cell layers the nuclei were seen as disks of varying intensities. In pre-cancerous lesions the keratin thickness and cell nuclear density were found to be increased when compared to normal controls. In OSMF cases confocal images of fibrosis show scattering from individual fibres as hyperdense areas. Oral squamous cell carcinoma cases demonstrated extensive variations in cell size, nuclear size and nuclear morphology. At cellular level, dysplastic features like increased nuclear density, increased nuclear cytoplasmic ratio, nuclear and cellular pleomorphism with loss of cohesiveness were identified in all five cases.Our results support the potential of reflectance confocal microscopy to play a significant role in clinical evaluations of oral lesions, early diagnosis of potentially malignant and malignant oral lesions and real time identification of tumour margins.

Impact of second primary esophageal or lung cancer on survival of patients with head and neck cancer - Corrected Proof

2010-02-08

Summary: Second cancers following head and neck cancer (HNC) most often involve the esophagus and lung, yet the actual magnitude of impact of second primary esophageal or lung cancer on survival of HNC patients has not been well established, particularly by a large-scale epidemiological study. To provide a quantitative estimate of the survival impact, we conducted a population-based study including 63,720 cases of HNC subsets, of which 3658 developed at least one second primary malignancy, 253 had a second esophageal cancer and 388 had a second lung cancer. A Cox proportional hazards model which included age at initial cancer diagnosis and gender were employed to compare the survival rates between patients with different types of second cancers. Our results showed that the second esophageal or lung cancer contributed to a poorer outcome than the other types of second cancer, regardless of the index tumor site (all Ps⩽0.019). The overall median survival was 0.76±0.04 and 0.72±0.08years for second esophageal and lung cancers, respectively. Compared to those without second cancers, the patients with second esophageal or lung cancer were associated with a significant reduction in survival, with an estimated 31–105% excess risk of death according to the site of the primary index tumor. In conclusion, the second esophageal and lung cancers have a significantly negative impact on the survival of HNC patients, thereby calling for a more effective program for surveillance and chemoprevention for these two sites.

Arecoline arrests cells at prometaphase by deregulating mitotic spindle assembly and spindle assembly checkpoint: Implication for carcinogenesis - Corrected Proof

2010-02-08

Summary: One apparent feature of cancerous cells is genomic instability, which may include various types of chromosomal aberrations, such as translocation, aneuploidy, and the presence of micronuclei inside the cells. Mutagenic factors that promote the emergence of genomic instability are recognized as risk factors for the development of human malignancies. In Asia, betel quid (BQ) chewing is one of such risk factors for oral cancer. Areca nut is an essential constitute of BQ and is declared as a group I carcinogen by the International Agency for Research on Cancer. However, the molecular and cellular mechanisms regarding the carcinogenicity of areca nut are not fully explored. Here we reported that arecoline, a major alkaloid of areca nut, could arrest cells at prometaphase with large amounts of misaligned chromosomes. This prometaphase arrest was evidenced by condensed chromosome pattern, increased histone H3 phosphorylation, and accumulation of mitotic proteins, including aurora A and cyclin B1. To investigate the molecular mechanisms accounting for arecoline-induced prometaphase arrest, we found that arecoline could stabilize mitotic spindle assembly, which led to distorted organization of mitotic spindles, misalignment of chromosomes, and up-regulation of spindle assembly checkpoint (SAC) genes. The SAC proteins BubR1 and Mps1 were differentially modified between the cells treated with arecoline and nocodazole. This together with aurora A overexpression suggested that SAC might be partly suppressed by arecoline. As a result, the arecoline-exposed cells might produce progeny that contained various chromosomal aberrations and exhibited genomic instability.

Nuclear Survivin expression is correlated with malignant behaviors of head and neck cancer together with Aurora-B - Corrected Proof

2010-02-08

Summary: Survivin belongs to the inhibitors of apoptosis (IAP) gene family and inhibits apoptosis. Besides its role as IAP, Survivin recently appears to function as a subunit of the chromosomal passenger complex (CPC) for regulating cell division with other CPC proteins including Aurora-B and INCENP. Nuclear Survivin is suspected to control cell division, whereas cytoplasmic Survivin is considered cytoprotective. Although there are several studies on Survivin expression and its function as inhibition of apoptosis, there is no study on Survivin function as a CPC and its correlation with other CPC proteins in head and neck squamous cell carcinoma (HNSCC). Here, therefore, we examined nuclear Survivin expression and its functional correlation with Aurora-B in HNSCC. High expression of Survivin was well correlated with Aurora-B expression in nuclear fraction of HNSCC cell lines and tissues. Moreover, nuclear Survivin expression was significantly correlated with Ki-67 and Aurora-B expression by immunohistochemistry. Notably, HNSCC cases with nuclear Survivin and Aurora-B expression exhibited marked malignant behaviors. Interestingly, both Survivin and Aurora-B knockdown inhibited cell growth and tumorsphere formation. Overall suggest that nuclear Survivin may be involved in tumor progression together with Aurora-B, and that Survivin and Aurora-B can be useful diagnostic markers and therapeutic targets.

Multivariate analyses to assess the effect of surgeon volume on survival rate in oral cancer: A nationwide population-based study in Taiwan - Corrected Proof

Ching-Chih Lee, Hsu-Chueh Ho, Pesus Chou — 2010-02-08

Summary: Patients with oral cancer utilize considerable health care resources, particularly when wide resection of the tumor and reconstruction with pedicle flap/free flap is performed. This study was conducted to explore the relationship between survival rates and surgeon volume. A total of 1256 patients who underwent resections for oral cancer in 2005 were identified from the Taiwan National Health Insurance Research Database. Survival analysis, the Cox proportional regression model, and propensity score were used to evaluate the association between 3-year survival rates and surgeon caseloads. Oral cancer patients treated by high-volume surgeons (caseload 22–117) had better survival rates (hazard ratio [HR]=0.656; 95% confidence interval [CI], 0.484–0.89; P=0.007) using the Cox proportional regression model after adjusting for patients’ comorbid conditions, hospital, and surgeon characteristics. When analyzed by propensity score, the adjusted 3-year survival rate was 74% for patients treated by high-volume surgeons compared to 58% in the low/medium-volume group (P=0.019). We concluded that for patients who underwent oral cancer resection and reconstruction, after adjusting for differences in the case mix, high-volume surgeons had better 3-year survival rates. Treatment strategies adopted by high-volume surgeons should be analyzed further and utilized more widely.

Potential biomarkers in saliva for oral squamous cell carcinoma - Corrected Proof

2010-02-08

Summary: Sensitive and reliable early diagnostic markers for oral squamous cell carcinoma (OSCC) remain unavailable. Early identification of recurrence for OSCC is also a challenge. Unlike the other deep cancers, OSCC is located in oral cavity. The DNA, RNA, and protein derived from the living cancer cells and inflammatory cells then can be conveniently obtained from saliva. High-throughput genomic and proteomic approaches have been carried out to identify the potential biomarkers in body fluids such as saliva and blood for diagnosis and prognosis of OSCC. This article reviewed the recently identified biomarkers from saliva for OSCC. In addition, the biomarkers which have been correlated with OSCC tumor malignancy by molecular pathology analysis are also described. Finally, the potential biomarkers that have been demonstrated to associate with the malignant OSCC may be used for salivary screening for high-risk patients are suggested. This article may help to identify the potential biomarkers for screening and the molecular pathology analysis for high-risk patients of OSCC. Effective screening to identify high-risk patients can allow the clinician to provide the appropriate treatment without delay and to reduce the recurrence of OSCC.

Surgical outcomes and prognostic factors of oral cancer associated with betel quid chewing and tobacco smoking in Taiwan - Corrected Proof

2010-02-08

Summary: Oral squamous cell carcinoma (OSCC) is one of the most common cancers in geographic regions where betel quid (BQ) chewing is prevalent; OSCC is an extremely malignant neoplasm whose prognostic factors are multiple and complex. The purpose of this study was to assess clinicopathological prognostic factors and treatment outcomes in 698 consecutive OSCC patients who had undergone surgery as the primary treatment in an area with a high prevalence of both betel quid chewing and tobacco smoking. The prognostic factors were predicted using Cox’s proportional-hazards regression model, and the survival rate was calculated using Kaplan–Meier analysis. The median followup for all patients was 44months. The 5-year cumulative overall, disease-specific, and locoregional control survival rates were 61%, 62%, and 46%, respectively. Multivariate analysis showed that the lower level of nodal metastasis, advanced stage, tumor thickness >7mm, and treatment failures were independent risk factors of overall survival. Furthermore, history of alcohol drinking, lower level of nodal metastasis, advanced stage, poor cell differentiation, and treatment failures were independent predictors of poor disease-specific survival. However, we did not find any significant factor that affected locoregional recurrence. Due to the high frequencies of locoregional recurrence and second primary cancer, our findings emphasize that aggressive surgical excision, adjuvant treatments according to clinicopathological prognostic factors and close surveillance are important to the survival of OSCC patients in an area with a high prevalence of betel quid chewing and tobacco smoking.