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Oral Cancer

Information for Patients and the Public
Information for Health Professionals / Researchers
Latest Research Publications
Salivary Gland Cancer
Molecular Biology of Oral Cancers

Information Patients and the Public (12 links)


Information for Health Professionals / Researchers (13 links)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Ouyang DQ, Liang LZ, Zheng GS, et al.
Risk factors and prognosis for salivary gland adenoid cystic carcinoma in southern china: A 25-year retrospective study.
Medicine (Baltimore). 2017; 96(5):e5964 [PubMed] Free Access to Full Article Related Publications
Adenoid cystic carcinoma (ACC) is characterized by slow growth, frequent local recurrences, and high incidence of distant metastasis (DM). The aim of this study was to evaluate predictive factors for local-regional (LR) recurrence, DM, and survival in ACC.A retrospective review of the medical records for patients with salivary glands ACC from 1990 to 2015 was performed. The clinical parameters were assessed to identify correlations with the development of LR recurrence, DM, and survival of these patients.Among 228 patients who underwent surgery as definitive treatment, 210 (92.1%) were followed up in the study. DM was detected in 64 (30.5%) patients, LR recurrence was detected in 58 (27.6%) patients. The estimated 5, 10, and 15-year overall survival rates were 84.7%, 70.8%, and 34.0%, respectively. Multivariate analysis revealed that the presence of lymphovascular invasion and a high T classification were very strong adverse factors, which independently influenced LR recurrence, DM, and survival of ACC patients. Positive/close margin and N+ status were independent risk factors for DM and LR recurrence, respectively. Survival of ACC patents was also affected by tumor location.Presence of lymphovascular invasion and a high T classification were very strong adverse factors and independent predictors for ACC patients' prognosis, which influenced LR control, DM control, and survival.

Lin X, Khalid S, Qureshi MZ, et al.
VEGF mediated signaling in oral cancer.
Cell Mol Biol (Noisy-le-grand). 2016; 62(14):64-68 [PubMed] Related Publications
Increasingly it is being realized that oral cancer arises from genetic/epigenetic mutations, dysregulations of spatio-temporally controlled signal transduction cascades and loss of apoptosis. Epidemiological studies have provided a stronger association between tobacco use (chewed and smoked) and oral cancer. Nevertheless, alcohol has also gained attention as a significant risk factor, having a multiplicative synergistic cancer promoting effect with tobacco. Vascular Endothelial Growth Factor (VEGF) mediated signaling has gained limelight because of its instrumental role in endothelial cell proliferation, survival, invasion, migration, chemotaxis of bone marrow (BM)-derived progenitor cells, vasodilation and vascular permeability. In this review we provide most recent updates on involvement of VEGF/VEGFR signaling axis in oral cancer. We partition this multi-component review into different sections and summarize latest advancements related to therapies against VEGF/VEGFR signaling axis and how microRNAs tactfully modulate VEGF and VEGFR in oral cancers. Data obtained through preclinical and clinical studies has revealed that therapeutic benefits associated with VEGF-targeted therapy are complicated in different cancers and involve myriad of mechanisms. A better understanding of VEGF/VEGFR mediated signaling in oral cancers and testing of novel therapeutic agents in preclinical models will prove to be helpful in effective translation of safest drugs from benchtop to the bedside.

Vishwakarma S, Agarwal R, Goel SK, et al.
Altered Expression of Sphingosine-1-Phosphate Metabolizing Enzymes in Oral Cancer Correlate With Clinicopathological Attributes.
Cancer Invest. 2017; 35(2):139-141 [PubMed] Related Publications
We have determined the gene expression of sphingosine-1-phosphate (S1P) metabolizing enzymes (SphK1, SphK2, SGPL1, SGPP1, SGPP2, PPAP2A, PPAP2B, and PPAP2C) by quantitative real-time polymerase chain reaction in tumor tissues and adjacent normal tissues of 50 oral squamous cell carcinoma (OSCC) patients. Expression of SphK1 and SGPP1 genes was up-regulated significantly in 70% and 75% OSCC tumors respectively. Importantly, expression of SphK2 and PPAP2B was down-regulated in the tumor tissues of 70% OSCC patients. Expression of SphK2 and PPAP2B negatively correlated with tumor-node-metastasis (TNM) staging and tumor volume respectively. Furthermore, LPP1 is an independent predictor of TNM staging and lymph node ratio.

Hsieh R, Nico MM, Camillo CM, et al.
Mutational Status of NRAS and BRAF Genes and Protein Expression Analysis in a Series of Primary Oral Mucosal Melanoma.
Am J Dermatopathol. 2017; 39(2):104-110 [PubMed] Related Publications
Primary oral mucosal melanoma is an extremely rare and aggressive tumor arising from melanocytes located in the mucosal epithelium of the oral cavity. Although malignant melanoma of oral mucosa shares some clinical features with its cutaneous counterpart, it has been associated with a worst prognosis; its etiopathogenesis are still only partially unraveled as there is no influence of UV radiation. It is known that the mitogen-activated protein kinase pathway mediates cellular responses to growth signals and its activation is an important phenomenon in melanoma. The aim of this study was to evaluate NRAS and BRAF genes, both components of mitogen-activated protein kinase molecular pathway, and compare with their protein expression. Point mutations of NRAS (codons 12, 13, and 61) and BRAF (codon 600) were screened by pyrosequencing method, and its results were associated to the protein expression of RAS and BRAF performed by immunohistochemistry. The authors observed mutation in BRAF 600 (3/14), NRAS codons 12 and 13 (2/14), and NRAS codon 61 (2/8). One case showed positive RAS protein expression, but no mutation was observed. Twelve in 14 cases showed positive BRAF protein expression: 3 cases showed BRAF mutation; 2 cases showed NRAS codon 61 mutation; 2 cases showed NRAS codons 12 and 13 mutation but not simultaneously. Although NRAS and BRAF mutation frequency and RAS protein expression are low, BRAF protein expression was intense; probably, NRAS and BRAF mutations are independent events and alternative molecular mechanisms in the primary oral mucosal melanoma tumorigenesis.

Noda Y, Kishino M, Sato S, et al.
Galectin-1 expression is associated with tumour immunity and prognosis in gingival squamous cell carcinoma.
J Clin Pathol. 2017; 70(2):126-133 [PubMed] Related Publications
AIMS: Galectin-1 (Gal-1) is a β-galactoside-binding protein that overexpresses in cancer and plays pivotal roles in tumour progression. Gal-1 regulates angiogenesis and invasiveness, and suppresses tumour immunity by inducing T cell apoptosis. Several studies have examined the relationship between Gal-1 and tumour immunosuppression in vivo, but they have not examined the clinicopathological relationship between Gal-1 expression and apoptotic T cell number in human tissue. In this study, we investigated the association between Gal-1 expression and apoptotic T cells of gingival squamous cell carcinoma (GSCC), as well as other clinicopathological factors.
METHODS: Immunohistochemical investigation of 80 GSCC specimens using anti-Gal-1, anti-CD3, anti-CD4, anti-CD8, anti-CD34, antipodoplanin and anticleaved caspase-3 (CC-3) antibodies was performed. Relative expression levels of CD3 and CC-3, as well as CD8 and CC-3 were assessed simultaneously by double immunostaining. Gal-1 expression and T cell apoptosis were evaluated in 6 high-power fields (3 in the tumour and 3 in the stroma).
RESULTS: Gal-1 expression in GSCC was significantly correlated with T cell infiltration (p=0.036), and apoptosis of CD3+ and CD8+ T cells (p<0.001). Moreover, Gal-1 expression was significantly correlated with lymph node metastasis (p=0.021), histological differentiation (p<0.001) and overall survival rate (p=0.021).
CONCLUSIONS: These findings suggest that Gal-1 plays an important role in immune escape of GSCC cells, and Gal-1 expression level may be a useful clinicopathological prognostic marker for GSCC.

Zhang CZ
Long non-coding RNA FTH1P3 facilitates oral squamous cell carcinoma progression by acting as a molecular sponge of miR-224-5p to modulate fizzled 5 expression.
Gene. 2017; 607:47-55 [PubMed] Related Publications
A growing body of evidence has indicated that long non-coding RNAs (lncRNAs) function as competing endogenous RNAs (ceRNAs) during tumorigenesis. In this study, the qRT-PCR results revealed that the lncRNA ferritin heavy chain 1 pseudogene 3 (FTH1P3) was over-expressed in oral squamous cell carcinoma (OSCC) and decreased the survival rate of OSCC patients. Ectopic expression of FTH1P3 facilitates cell proliferation and colony formation in OSCC cells. Moreover, FTH1P3 acted as a competitive endogenous RNA (ceRNA), effectively becoming sponge for miR-224-5p and thereby modulating the expression of fizzled 5. Importantly, expression analysis revealed that both FTH1P3 and fizzled 5 were up-regulated in OSCC cell lines and tissues, and over-expression of fizzled 5 also functioned as an oncogene in OSCC cells. Our data demonstrated FTH1P3 facilitated OSCC progression by acting as a molecular sponge of miR-224-5p to modulate fizzled 5 expression. Thus, targeting the ceRNA network referring FTH1P3 may be a therapeutic target for treatment of OSCC.

Ferreira JC, Oton-Leite AF, Guidi R, Mendonça EF
Granular cell tumor mimicking a squamous cell carcinoma of the tongue: a case report.
BMC Res Notes. 2017; 10(1):14 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Granular cell tumor is a rare benign tumor that can present a pseudoepitheliomatous hyperplasia of the covering epithelium. This lesion is not encapsulated and can be characterized by a pseudo invasive growth pattern, represented by the tumoral cells that infiltrate between adjacent connective tissue elements. Diagnostic difficulties may arise because histopathological features of the pronounced pseudoepitheliomatous hyperplasia can be confused with a well-differentiated oral squamous cell carcinoma. The aim of this case report is to demonstrate the role of an immunohistochemical panel in the diagnosis of a granular cell tumor in the tongue with clinical and microscopic features resembling an oral squamous cell carcinoma.
CASE PRESENTATION: A 44-year-old white man with a history of heavy smoking and alcohol abuse presented an ulcerated nodular lesion in the dorsum of the tongue. The lesion was asymptomatic with fast growth. The clinical diagnosis was an oral squamous cell carcinoma. An incisional biopsy was performed and the ensuing histopathological analysis showed a pseudoepitheliomatous hyperplasia in the overlying epithelium mimicking the invasion of epithelial tumor cells into the connective tissue as in an oral squamous cell carcinoma. Immunohistochemical antibodies (S-100, vimentin, CD68, p53, Ki-67, E-cadherin, collagen IV and cytokeratin AE1/AE3) were used to characterize molecular aspects of the lesion. Strong staining of S-100 protein, CD68, vimentin, E-cadherin and low proliferative activity observed with Ki-67 expression confirmed the diagnosis of a granular cell tumor. The patient was submitted to surgical excision of the whole lesion. At a 12-month check-up, there was no evidence of recurrence.
CONCLUSION: This case report showed that the immunohistochemical profile was helpful in determining the clinical behavior of the tumor and establishing the final diagnosis with appropriate treatment.

Torres KG, Carle L, Royer M
Nevus Spilus (Speckled Lentiginous Nevus) in the Oral Cavity: Report of a Case and Review of the Literature.
Am J Dermatopathol. 2017; 39(1):e8-e12 [PubMed] Related Publications
The congenital melanocytic nevus is a pigmented melanocytic lesion that presents at birth or shortly thereafter. It is commonly described on the skin, usually on the trunk and extremities. Only five intraoral cases of congenital melanocytic nevi have been described in the English literature. A nevus spilus (speckled lentiginous nevus) is a clinical variant of congenital melanocytic nevus. The authors present the case of a 19-year-old male with an intraoral nevus spilus. The anterior mandibular gingiva exhibited multiple speckled, pigmented papules and macules on a thickened, hyperplastic macular background. Microscopic examination revealed characteristic morphologic features of intramucosal nevi extending into the deep portions of the submucosa. Although other authors have reported similar clinical presentation in the oral mucosa, no other case reports were found in the English literature classifying an intraoral congenital nevus as an intraoral nevus spilus. The sixth case of an intraoral congenital melanocytic nevus and the first case subclassified as an intraoral nevus spilus (speckled lentiginous nevus) is reported, with a review of the literature.

Critchlow D
Part 2: Oral health care for the housebound patient.
Br J Community Nurs. 2017; 22(1):650-657 [PubMed] Related Publications
Oral disease can have a significant impact on the health and wellbeing of the housebound patient. The aetiology of oral conditions such as dental caries and periodontal disease have been well investigated and there is a solid evidence base in how to best prevent their progress. The Department of Health document Delivering better oral health: an evidence-based toolkit for prevention is a valuable resource that outlines the current best preventative evidence in the form of practical advice for clinicians and patients. This article aims to distil and present this advice for the benefit of community nurses. It will identify areas of particular importance for people with additional needs, particularly the elderly and infirm. Outlining how to best tailor preventative advice and treatment for this patient group.

Chiou SJ, Lin W, Hsieh CJ
Assessment of duration until initial treatment and its determining factors among newly diagnosed oral cancer patients: A population-based retrospective cohort study.
Medicine (Baltimore). 2016; 95(50):e5632 [PubMed] Free Access to Full Article Related Publications
Few studies have focused on the early treatment stages of cancer, and the impact of treatment delay on oncologic outcomes is poorly defined. We used oral cancer as an example to investigate the distribution of durations until initial treatment.This study was conducted using the National Health Insurance Research Database, which is linked to Taiwan's Cancer Registry and Death Registry databases. We defined "cutoff points for first-time treatment" according to a weekly schedule and sorted the patients into 2 groups based on whether their duration until initial treatment was longer or shorter than each cutoff. We then calculated the Kaplan-Meier estimator to determine the difference in survival rates between the 2 groups and performed logistic regression to identify determining factors.The average time between diagnosis and initial treatment was approximately 22.45 days. The average survival duration was 1363 days (standard deviation: 473.06 days). Oral cancer patients had no statistically significant differences in survival until a cutoff point of 3 weeks was used (with survival duration 71 days longer if initial treatment was received within 3 weeks). Patients with higher incomes or higher Charlson comorbidity index scores and patients treated at a hospital in a region with medium urbanization had lower likelihoods of treatment delay, whereas older patients were at higher risk of treatment delay.The attitudes, beliefs, and social contexts of oral cancer patients influence the treatment-seeking behaviors of these patients. Therefore, the government should advocate the merits of the referral system for cancer treatment or improve quality assurance for cancer diagnoses across different types of hospitals. Health authorities should also educate patients or use a case manager to encourage prompt treatment within 3 weeks and should provide screening and prevention services, particularly for high-risk groups, to reduce mortality risk.


Cervical lymph node metastasis in adenoid cystic carcinoma of the major salivary glands.
J Laryngol Otol. 2017; 131(2):96-105 [PubMed] Related Publications
OBJECTIVE: To verify the prevalence of cervical lymph node metastasis in adenoid cystic carcinoma of major salivary glands, and to establish recommendations for elective neck treatment.
METHODS: A search was conducted of the US National Library of Medicine database. Appropriate articles were selected from the abstracts, and the original publications were obtained to extract data.
RESULTS: Among 483 cases of major salivary gland adenoid cystic carcinoma, a total of 90 (18.6 per cent) had cervical metastasis. The prevalence of positive nodes from adenoid cystic carcinoma was 14.5 per cent for parotid gland, 22.5 per cent for submandibular gland and 24.7 per cent for sublingual gland. Cervical lymph node metastasis occurred more frequently in patients with primary tumour stage T3-4 adenoid cystic carcinoma, and was usually located in levels II and III in the neck.
CONCLUSION: Adenoid cystic carcinoma of the major salivary glands is associated with a significant prevalence of cervical node metastasis, and elective neck treatment is indicated for T3 and T4 primary tumours, as well as tumours with other histological risk factors.

Cai WX, Zheng LW, Ma L, et al.
Tumorigenicity and Validity of Fluorescence Labelled Mesenchymal and Epithelial Human Oral Cancer Cell Lines in Nude Mice.
Biomed Res Int. 2016; 2016:4897986 [PubMed] Free Access to Full Article Related Publications
Tumorigenicity and metastatic activity can be visually monitored in cancer cells that were labelled with stable fluorescence. The aim was to establish and validate local and distant spread of subcutaneously previously injected fluorescence transduced human tongue cancer cell lines of epithelial and mesenchymal phenotype in nude mice. A total of 32 four-week-old male athymic Balb/c nude mice were randomly allocated into 4 groups (n = 8). A single dose of 0.3 mL PBS containing 1 × 107 of four different cancer cell-lines (UM1, UM1-GFP, UM2, and UM2-RFP) was injected subcutaneously into the right side of their posterolateral back. Validity assessment of the labelled cancer cells' tumorigenicity was assessed by physical examination, imaging, and histology four weeks after the injection. The tumor take rate of cancer cells was similar in animals injected with either parental or transduced cancer cells. Transduced cancer cells in mice were easily detectable in vivo and after cryosection using fluorescent imaging. UM1 cells showed increased tumor take rate and mean tumor volume, presenting with disorganized histopathological patterns. Fluorescence labelled epithelial and mesenchymal human tongue cancer cell lines do not change in tumorigenicity or cell phenotype after injection in vivo.

Zhu L, Shen Y, Sun W
Paraoxonase 3 promotes cell proliferation and metastasis by PI3K/Akt in oral squamous cell carcinoma.
Biomed Pharmacother. 2017; 85:712-717 [PubMed] Related Publications
Paraoxonase 3 (PON3) is an oncogene in cancer, however, little is known about the mechanisms and roles of PON3 in oral squamous cell carcinoma (OSCC), which is the aim of our study. We found that the expression of PON3 was up-regulated in OSCC samples and cell lines. PON3 was associated with accelerating cell proliferation, cell cycle, migration and invasion in OSCC cells. Further research showed that PON3 was regulated by PI3K/Akt pathway. We also found that AP-1 was an important transcriptional factor regulating PON3 expression in OSCC. The study elucidates that PI3K/Akt pathway up-regulated the expression of PON3 in OSCC by AP-1.

Han MW, Lee JC, Park SY, et al.
Homotypic Interaction of Stabilin-2 Plays a Critical Role in Lymph Node Metastasis of Tongue Cancer.
Anticancer Res. 2016; 36(12):6611-6618 [PubMed] Related Publications
BACKGROUND/AIM: Lymph node (LN) metastasis of solid types of tumors has important clinical significance and it is therefore critical to identify molecular biomarkers that would enable the selection of patients with LN metastases.
PATIENTS AND METHODS: We evaluated the expression of stabilin-2 in primary oral tongue tumors and metastatic LNs using immunohistochemical staining. The correlation between risk factors and nodal metastasis was assessed and disease-free survival was analyzed.
RESULTS: Stabilin-2 expression remained a significant predictor of LN metastasis and the factor affecting recurrence in tongue cancer. Most importantly, all metastatic tumors of tongue, lung, stomach and colon cancers stained positive for stabilin-2 and stabilin-2 was expressed strongly in the sinusoidal endothelial cell of metastatic LNs.
CONCLUSION: Stabilin-2 can play a critical role in the first entrapping step of LN metastasis through homotypic interaction with the lymphatic endothelium and appears to be a tumor biomarker predicting for LN metastasis in patients with solid tumors.

Obata K, Shimo T, Okui T, et al.
Tachykinin Receptor 3 Distribution in Human Oral Squamous Cell Carcinoma.
Anticancer Res. 2016; 36(12):6335-6341 [PubMed] Related Publications
BACKGROUND: Tachykinin 3 (TAC3) and its preferred tachykinin receptor 3 (TACR3) that are prominently detected in the central nervous system, play significant roles in physiological development and specifically in the human reproductive system. The roles of TAC3/TACR3 in oral squamous cell carcinoma are unknown.
MATERIALS AND METHODS: We examined the expression pattern of TAC3/TACR3 in clinically-resected oral squamous cell carcinoma samples using immunohistochemistry and immunofluorescence analysis.
RESULTS: We found that even though the expression level of TACR3 was negative in the normal epithelium, it was highly elevated in tumor cells. A more intense signal was observed in the invasive front of tumor cells that had migrated into the mandible bone matrix. TAC3 was not detected in tumor cells, but was expressed in PGP-9.5-positive sensory nerves in the mandible.
CONCLUSION: Our results suggest that peripheral sensory nerve-derived TAC3 may affect gingival oral squamous cell carcinoma cells through TACR3 in the bone matrix.

Gharat SA, Momin M, Bhavsar C
Oral Squamous Cell Carcinoma: Current Treatment Strategies and Nanotechnology-Based Approaches for Prevention and Therapy.
Crit Rev Ther Drug Carrier Syst. 2016; 33(4):363-400 [PubMed] Related Publications
Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer; it involves damage to oral epithelial cells due to accumulation of multiple genetic mutations in the cells. OSCC remains major cause of morbidity and mortality in patients with head and neck cancers. Tobacco, smoking, alcohol consumption alone or with chewing tobacco, and betel quid are potential carcinogens contributing to the high occurrence of OSCC. Current treatment modalities for OSCC like chemoradiotherapy, surgery, EGFR inhibitors and COX-2 inhibitors, and photodynamic therapy have led to the major problems related to non-specific cell death. Nanoengineered systems offer solutions to these problems that not only minimize the major drawbacks of nonspecific cell death but also maximize the efficacy of the cancer therapeutic agents. Various efficacious nanotechnology-based carrier systems are being widely investigated for their potential in OSCC treatment: polymeric nanoparticles, polymeric micelles, nanoemulsions and layered nanoemulsions, nanoliposomes, solid lipid nanoparticles and nanolipid carriers, cyclodextrin complexes, hydrogels, metallic nanoparticles, nanocarbon tubes, and receptor mediated drug delivery systems. We highlight the etiology, line of the treatment and chemopreventive measures related to OSCC. We focus on data available in the research carried out worldwide in past 15 years related to the management of OSCC.

Jin L, Miao J, Liu Y, et al.
Icaritin induces mitochondrial apoptosis by up-regulating miR-124 in human oral squamous cell carcinoma cells.
Biomed Pharmacother. 2017; 85:287-295 [PubMed] Related Publications
AIM OF THE STUDY: The present study is aimed to investigate the apoptosis-inducing effect of icaritin in human oral squamous cell carcinoma (OSCC) cells and the associated mechanisms.
MATERIALS AND METHODS: KB and SCC9 cell lines were used as model cell lines. Effect of icaritin on apoptosis was analyzed by flow cytometry. The effect of icaritin on mitochondrial apoptotic pathway was demonstrated by loss of mitochondrial membrane potential and release of cytocrome C from mitochondria. MiR-124 mimic and miR-124 inhibitor were used to manipulate the expression of miR-124 in OSCC cells. SiRNA targeting Sp1 and DNMT1 as well as Sp1 and DNMT1 overexpressing vector were utilized to confirm their roles in the apoptosis-inducing effect of icaritin in OSCC cells. Activation of relevant signaling pathway by icaritin and effect of icaritin on expression of targeting molecules were determined by western blots or qRT-PCR.
RESULTS: Our results showed that icaritin inhibited tumor cell viability in a dose- and time-dependent manner, and induced cell apoptosis via intrinsic mitochondrial pathway by upregulating miR-124. Moreover, our results showed that the icaritin exerted regulatory effect on miR-124 through suppressing Sp1/DNMT1 signaling.
CONCLUSION: Our data provide the first experimental evidence that icaritin induces mitochondrial apoptosis in OSCC cells by upregulating miR-124 and suggest a new mechanism to explain its anti-tumor effects.

Lundberg M, Munsterhjelm B, Mäkitie A, Leivo I
Immunohistochemical Staining of Histological Fragments Derived from Salivary Gland Tumour Fine-Needle Biopsy Aspirates.
Acta Cytol. 2017; 61(1):17-20 [PubMed] Related Publications
OBJECTIVES: The aim of this study was to describe a method for analysing histological fragments derived from fine- needle aspirate biopsy (FNAB) of salivary gland tumours (SGTs), and to evaluate the use of immunohistochemistry (IHC) on them.
STUDY DESIGN: We reviewed all 509 FNAB pathology reports taken from SGTs at Helsinki University Hospital, Finland, between 1999 and 2009. In 51% of the cases (n = 209) "histo-fragments" had been obtained and 31 had been further analysed by IHC. Of these, 25 (81%) were available for review. We evaluated the benefit of IHC by relating its added value to the preoperative cytological diagnosis and its accuracy compared with the postoperative histological diagnosis.
RESULTS: Most of the samples analysed by IHC were assigned a malignant diagnosis, with 12 different types of malignancy represented. IHC was advantageous in 76% of the cases. In the 108 studies using IHC in this series, antibodies to 36 different antigens were used.
CONCLUSION: Analysis of histo-fragments in FNABs using IHC can be valuable in specific differential diagnostics and raises diagnostic accuracy in SGTs.

Abdul-Razak M, Chung H, Wong E, et al.
Sentinel lymph node biopsy for early oral cancers: Westmead Hospital experience.
ANZ J Surg. 2017; 87(1-2):65-69 [PubMed] Related Publications
BACKGROUND: Sentinel lymph node biopsy (SLNB) has become an alternative option to elective neck dissection (END) for early oral cavity squamous cell carcinoma (OCSCC) outside of Australia. We sought to assess the technical feasibility of SLNB and validate its accuracy against that of END in an Australian setting.
METHODS: We performed a prospective cohort study consisting of 30 consecutive patients with cT1-2 N0 OCSCC referred to the Head and Neck Cancer Service, Westmead Hospital, Sydney, between 2011 and 2014. All patients underwent SLNB followed by immediate selective neck dissection (levels I-III).
RESULTS: A total of 30 patients were diagnosed with an early clinically node-negative OCSCC (seven cT1 and 23 cT2), with the majority located on the oral tongue. A median of three (range: 1-14) sentinel nodes were identified on lymphoscintigraphy, and all sentinel nodes were successfully retrieved, with 50% having a pathologically positive sentinel node. No false-negative sentinel nodes were identified using selective neck dissection as the gold standard. The negative predictive value (NPV) of SLNB was 100%, with 40% having a sentinel node identified outside the field of planned neck dissection on lymphoscintigraphy. Of these, one patient had a positive sentinel node outside of the ipsilateral supraomohyoid neck dissection template.
CONCLUSION: SLNB for early OCSCC is technically feasible in an Australian setting. It has a high NPV and can potentially identify at-risk lymphatic basins outside the traditional selective neck dissection levels even in well-lateralized lesions.

Otsuka Y, Sato H, Oikawa T, et al.
High expression of EPB41L5, an integral component of the Arf6-driven mesenchymal program, correlates with poor prognosis of squamous cell carcinoma of the tongue.
Cell Commun Signal. 2016; 14(1):28 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Squamous cell carcinoma of the tongue (tongue SCC) is a major subtype of head and neck squamous cell carcinoma (HNSCC), which is an intractable cancer under current therapeutics. ARF6 and its effector AMAP1 are often overexpressed in different types of cancers, such as breast cancer and renal cancer, and in these cancers, AMAP1 binds to EPB41L5 to promote invasion, metastasis, and drug resistance. EPB41L5 is a mesenchymal-specific protein, normally induced during epithelial-mesenchymal transition (EMT) to promote focal adhesion dynamics. Similarly to breast cancer and renal cancer, the acquisition of mesenchymal phenotypes is the key process that drives the malignancy of HNSCC. We previously showed that the overexpression of AMAP1 in tongue SCC is statistically correlated with the poor outcome of patients. In this study, we examined whether tongue SCC also expresses EPB41L5 at high levels.
RESULTS: Immunohistochemical staining of clinical specimens of tongue SCC demonstrated that high expression levels of EPB41L5 statistically correlate with poor disease-free survival and poor overall survival rates of patients. The tongue SCC cell line SCC-9, which overexpress Arf6 and AMAP1, also expressed EPB41L5 at high levels to promote invasiveness, whereas the weakly invasive SCC-25 cells did not express EPB41L5 at notable levels. Among the different EMT-associated transcriptional factors, ZEB1 was previously found to be most crucial in inducing EPB41L5 in breast cancer and renal cancer. In contrast, expression levels of ZEB1 did not correlate with the expression levels of EPB41L5 in tongue SCC, whereas KLF8 and FOXO3 levels showed positive correlations with EPB41L5 levels. Moreover, silencing of EPB41L5 only marginally improved the drug resistance of SCC-9 cells, even when coupled with ionizing radiation.
CONCLUSION: Our results indicate that activation of the cancer mesenchymal program in tongue SCC, which leads to EPB41L5 expression, closely correlates with the poor prognosis of patients. However, ZEB1 was not the major inducer of EPB41L5 in tongue SCC, unlike in breast cancer and renal cancer. Thus, processes that trigger the mesenchymal program of tongue SCC, which drives their malignancies, seem to be substantially different from those of other cancers.

Lee DH, Yoon TM, Lee JK, Lim SC
Atheroma of the facial artery mimicking a parotid gland tumor: A case report.
Medicine (Baltimore). 2016; 95(46):e5403 [PubMed] Free Access to Full Article Related Publications
INTRODUCTION: Atheroma of the facial artery is an extremely rare disease.
CLINICAL FINDINGS/PATIENT CONCERNS: Herein, we report an extremely rare case of an atheroma arising from the facial artery, mimicking a parotid gland tumor.
DIAGNOSES: The preoperative diagnosis was a right-sided parotid gland tumor.
INTERVENTIONS: We performed removal of the right parotid gland tumor, via a modified face-lift incision.
OUTCOMES: Histological examination of the specimen revealed an atheroma of the facial artery.
CONCLUSION: Clinicians should consider atheroma in the differential diagnosis of tumors arising around the parotid gland.

Sarkar R, Dey S, Pal M, et al.
Risk prediction for oral potentially malignant disorders using fuzzy analysis of cytomorphological and autofluorescence alterations in habitual smokers.
Future Oncol. 2017; 13(6):499-511 [PubMed] Related Publications
AIM: This study aims to develop a novel noninvasive method for early cancer trend diagnosis in habitual smokers by corroborating cytomorphological and autofluorescence alterations.
MATERIALS & METHODS: A total of 120 subjects were included and categorized into nonsmoker, smoker and clinically diagnosed oral potentially malignant disorder (OPMD) patients. Oral exfoliative epithelial cells were studied through differential interference contrast and fluorescence microscopy. Fuzzy trend analysis was performed using measured parameters for determining the risk factors among smokers.
RESULTS: The risk assessment in this study showed a positive correlation of smoking duration with early cancer risk factors with a correlation co-efficient of 0.86.
CONCLUSION: Alterations in cellular morphology and autofluorescence intensities showed positive correlation with OPMD. The present study will benefit to investigate early prediction of OPMD among susceptible individuals.

Gaje PN, Amalia Ceausu R, Jitariu A, et al.
Mast Cells: Key Players in the Shadow in Oral Inflammation and in Squamous Cell Carcinoma of the Oral Cavity.
Biomed Res Int. 2016; 2016:9235080 [PubMed] Free Access to Full Article Related Publications
Although mast cells (MCs) have been discovered over 130 years ago, their function was almost exclusively linked to allergic affections. At the time being, it is well known that MCs possess a great variety of roles, in both physiologic and pathologic conditions. In the oral tissues, MCs release different proinflammatory cytokines, tumor necrosis factor alpha (TNF-α), that promote leukocyte infiltration in various inflammatory states of the oral cavity. These cells play a key role in the inflammatory process and, as a consequence, their number changes in different pathologic conditions of the oral cavity, like gingivitis, periodontitis, and so on. MCs also represent a rich source of proteases, especially of mast cell tryptase and chymase, which directly degrade the extracellular matrix through their proteolytic activity and thus indirectly stimulate angiogenesis and facilitate invasion and metastasis. It may be stated that mast cells could have an impact on primary tumor development, progression, and metastases in oral squamous cell carcinoma. By understanding the role of mast cells in the pathogenesis of different inflammatory and tumor diseases of the oral cavity, these cells may become therapeutic targets that could possibly improve the prognosis and survival of these patients.

Sood S, McGurk M, Vaz F
Management of Salivary Gland Tumours: United Kingdom National Multidisciplinary Guidelines.
J Laryngol Otol. 2016; 130(S2):S142-S149 [PubMed] Free Access to Full Article Related Publications
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. Salivary gland tumours are rare and have very wide histological heterogeneity, thus making it difficult to generate high level evidence. This paper provides recommendations on the assessment and management of patients with cancer originating from the salivary glands in the head and neck. Recommendations • Ultrasound guided fine needle aspiration cytology is recommended for all salivary tumours and cytology should be reported by an expert histopathologist. (R) • Adjuvant radiotherapy (RT) following surgery is recommended for all malignant submandibular tumours except in cases of small, low-grade tumours that have been completely excised. (R) • For benign parotid tumours complete excision of the tumour should be performed and offers good cure rates. (R) • In the event of intra-operative tumour spillage, most cases need long-term follow-up for clinical observation only. These should be raised in the multidisciplinary team to discuss the merits of adjuvant RT. (G) • As a general principle, if the facial nerve function is normal pre-operatively then every attempt to preserve facial nerve function should be made during parotidectomy and if the facial nerve is divided intra-operatively then immediate microsurgical repair (with an interposition nerve graft if required) should be considered. (G) • Neck dissection is recommended in all cases of malignant parotid tumours except for low-grade small tumours. (R) • Where malignant parotid tumours lie in close proximity to the facial nerve there should be a low threshold for adjuvant RT. (G) • Adjuvant RT should be considered in high grade or large tumours or in cases where there is incomplete or close resection margin. (R) • Adjuvant RT should be prescribed on the basis of clinical factors in addition to histology and grade, e.g. stage, pre-operative facial weakness, positive margins, peri-neural invasion and extracapsular spread. (R).

Kerawala C, Roques T, Jeannon JP, Bisase B
Oral cavity and lip cancer: United Kingdom National Multidisciplinary Guidelines.
J Laryngol Otol. 2016; 130(S2):S83-S89 [PubMed] Free Access to Full Article Related Publications
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. It provides recommendations on the assessment and management of patients with cancer of the oral cavity and the lip. Recommendations • Surgery remains the mainstay of management for oral cavity tumours. (R) • Tumour resection should be performed with a clinical clearance of 1 cm vital structures permitting. (R) • Elective neck treatment should be offered for all oral cavity tumours. (R) • Adjuvant radiochemotherapy in the presence of advanced neck disease or positive margins improves control rates. (R) • Early stage lip cancer can be treated equally well by surgery or radiation therapy. (R).

Butterworth C, McCaul L, Barclay C
Restorative dentistry and oral rehabilitation: United Kingdom National Multidisciplinary Guidelines.
J Laryngol Otol. 2016; 130(S2):S41-S44 [PubMed] Free Access to Full Article Related Publications
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK and provides recommendations on the pre-treatment oral and dental assessment, during and after treatment and oral rehabilitation. Restorative dentists are core members of the multidisciplinary team treating head and neck cancer patients, involved from the treatment planning phase through to long-term rehabilitation. Recommendations • Preventative oral care must be delivered to patients whose cancer treatment will affect the oral cavity, jaws, salivary glands and oral accessibility. (G) • Close working and communication between the surgeons, oncologists and restorative dental specialists is important in ensuring optimal oral health outcomes. (G) • Intensity-modulated radiotherapy has been shown to reduce long-term xerostomia and should be offered to all appropriate patients. (R) • If patients are deemed at risk of trismus they should be warned and its progressive and potentially irreversible nature explained. (G) • Where it is known that adjuvant radiotherapy will be given, extractions should take place at primary surgery to maximise the time for healing and minimise the number of surgical events for patients. (G) • Osseointegrated implants should be considered for all patients having resection for head and neck cancer. (G).

Jajodia E, Raphael V, Shunyu NB, et al.
Brush Cytology and AgNOR in the Diagnosis of Oral Squamous Cell Carcinoma.
Acta Cytol. 2017; 61(1):62-70 [PubMed] Related Publications
OBJECTIVE: We aimed to evaluate the role of brush cytology in the screening of oral lesions with malignant suspicion and compare it with histopathology in north-eastern India.
STUDY DESIGN: Brush cytology samples taken from 48 patients were processed for conventional cytology (CC) and liquid-based cytology (LBC), and biopsy samples were also obtained. LBC samples were also stained to assess the argyrophilic nucleolar organizer region (AgNOR). The cytology was compared with histopathology, both individually and in combination with AgNOR. The smear quality was compared with histopathology for evaluating their diagnostic accuracy.
RESULTS: The sensitivity of diagnosing oral cavity squamous cell carcinoma by LBC and CC alone was 75 and 85%, respectively, which improved on combining with the AgNOR count, with a cutoff of 6.5. The presence of round cells on cytology was significantly associated with high-grade lesions. LBC provided clearer cytomorphology but compromised the background information in high-grade lesions.
CONCLUSION: Brush cytology is a minimally invasive tool for screening oral lesions with malignant suspicion. LBC and CC are complementary techniques for cytological screening and combining them with AgNOR can increase the diagnostic yield. With objective criteria for assessment, cytology can be an indispensable tool for screening oral lesions in a resource-limited set-up, especially in high-incidence regions.

Li CX, Sun JL, Gong ZC, et al.
Prognostic value of GLUT-1 expression in oral squamous cell carcinoma: A prisma-compliant meta-analysis.
Medicine (Baltimore). 2016; 95(45):e5324 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: A variety of studies have evaluated the correlation between glucose transporter-1 (GLUT-1) expression and prognosis of oral squamous cell carcinoma (OSCC); however, the results were inconsistent and inconclusive. A meta-analysis was performed to assess the prognostic significance of GLUT-1 in OSCC.
METHODS: Electronic databases of PubMed, Embase, and Web of Science were searched for relevant studies. The last search was updated on July 2016. Odds ratio (OR) and 95% confidence interval (CI) were pooled to evaluate the relationship between GLUT-1 and clinical features and hazard ratio (HR) and 95% CI were combined to measure the effect of GLUT-1 on overall survival (OS). P value < 0.05 was considered as statistically significant.
RESULTS: A total of 13 studies with 1301 subjects were included for meta-analysis. The pooled data showed that high GLUT-1 expression was associated with advanced tumor stages (n = 7, OR = 2.99, 95% CI: 2.01-4.46, P < 0.001), higher tumor grade (n = 5, OR = 3.34, 95%CI: 1.12-9.94, P = 0.031), tumor size (n = 5, OR = 3.36, 95%CI: 2.04-5.51, P < 0.001), lymph node metastasis (n = 5, OR = 3.15, 95%CI: 1.89-5.25, P < 0.001), tobacco use (n = 3, OR = 2.18, 95%CI: 1.18-4.01, P = 0.013), and distant metastasis (n = 2, OR = 3.06, 95%CI: 1.19-7.9, P = 0.02). Furthermore, increased GLUT-1 expression was also correlated with shorter OS (n = 8, HR = 1.88, 95%CI: 1.51-2.33, P < 0.001). No significant publication bias was detected in this meta-analysis.
CONCLUSION: GLUT-1 overexpression was in connection with aggressive clinical features and worse OS in OSCC. However, further studies are still needed to verify whether GLUT-1 could serve as a prognostic biomarker for OSCC.

Tiwari S, Gupta PK, Bagbi Y, et al.
L-cysteine capped lanthanum hydroxide nanostructures for non-invasive detection of oral cancer biomarker.
Biosens Bioelectron. 2017; 89(Pt 2):1042-1052 [PubMed] Related Publications
In this paper, we present the result of studies related to the in situ synthesis of amino acid (L-Cysteine) capped lanthanum hydroxide nanoparticles [Cys-La(OH)3 NPs] towards the fabrication of efficient immunosensor for non-invasive detection of oral cancer. The characterization of Cys-La(OH)3 NPs was carried out by different techniques including X-ray diffraction, scanning electron microscopy, transmission electron microscopy, fourier transform infrared spectroscopy and electrochemical techniques. These Cys-La(OH)3 NPs were electrophoretically deposited onto an indium-tin-oxide glass substrate and used for immobilization of anti-cytokeratin fragment-21-1 (anti-Cyfra-21-1) for the electrochemical detection of Cyfra-21-1. This immunosensor shows a broad detection range of 0.001-10.2ngmL(-1), the low detection limit of 0.001ngmL(-1), and high sensitivity of 12.044µA (ng per mL cm(-2))(-1) with a response time of 5min. This immunosensor was found to be more advanced in terms of high sensitivity and low detection limit as compared to previously reported biosensors and commercially available ELISA kit (Kinesis DX).

Ansari SS, Akgün N, Berger MR
Erufosine increases RhoB expression in oral squamous carcinoma cells independent of its tumor suppressive mode of action - a short report.
Cell Oncol (Dordr). 2017; 40(1):89-96 [PubMed] Related Publications
PURPOSE: Recently, we found that erufosine (erucylphospho-N,N,N trimethylpropylammonium) can induce up-regulation of RhoB expression in oral squamous carcinoma (OSCC) cells, thereby hinting at a tumor suppressive role. Therefore, we aimed to evaluate the role of RhoB in the tumor suppressive mode of action of erufosine on OSCC cells.
METHODS: Anti-proliferative effects of erufosine were determined in HN-5 and FaDu OSCC-derived cells using a MTT assay. RhoB up-regulation was detected using microarray and qRT-PCR-based expression assays at IC25, IC50 and IC75 concentrations of erufosine. The results obtained were verified by Western blotting. In addition, siRNA-mediated RhoB knockdown was carried out and combined with erufosine treatment, after which cell cycle, colony formation and migration assays were performed to evaluate its combined effects.
RESULTS: We found that after erufosine treatment of HN-5 and FaDu cells for 24, 48 and 72 h the IC50 values ranged from 43 to 37 μM and 27- to 15 μM, respectively. Microarray and qRT-PCR-based expression analyses revealed RhoB up-regulation up to 9-fold and 20-fold, respectively. Using Western blotting, an increase in RhoB protein expression was observed, as well as a decrease in pAkt (Ser(473) and Thr(308)) expression and an increase in PARP cleavage. Combined siRNA-mediated RhoB knockdown and erufosine treatment resulted in slightly reduced RhoB and pAkt levels compared to erufosine treatment alone. Subsequent cell cycle analyses revealed an increased apoptotic induction, but a reduced G2 cell cycle arrest, of the combination. At the functional level, synergistic effects were observed using cell migration and colony formation assays.
CONCLUSIONS: Our data show that erufosine can cause up-regulation of RhoB expression in OSCC cells. Combining erufosine treatment with siRNA-mediated RhoB knockdown did, however, not reveal a role of RhoB in its tumor suppressive mode of action.

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