Decreased expression of Ep-CAM protein is significantly associated with the progression and prognosis of oral squamous cell carcinomas in Taiwan

Background:  The epithelial cell adhesion molecule (Ep-CAM) is involved in cell signaling, migration, proliferation, cell-cycle regulation, and cancer metastasis.
Methods:  This study used an immunohistochemical technique to examine the expression of Ep-CAM protein in 84 specimens of oral squamous cell carcinoma (OSCC), 98 specimens of oral epithelial dysplasia (OED, 31 mild, 41 moderate, and 26 severe OED cases), and 15 specimens of normal oral mucosa (NOM).
Results:  We found that the mean Ep-CAM labeling indices (LIs) decreased significantly from NOM (80 ± 18%) and mild OED (76 ± 14%) through moderate OED (66 ± 22%) and severe OED (55 ± 20%) to OSCC samples (46 ± 16%, P <  0.001). A significant correlation was found between the lower mean Ep-CAM LI and OSCCs with larger tumor size ( P =  0.003), positive lymph node metastasis ( P =  0.022), more advanced clinical stages ( P <  0.001), cancer recurrence ( P =  0.021), or extracapsular spread of lymph node ( P =  0.015). However, only Ep-CAM LI  <  50% ( P  < 0.0001) was identified as an independent unfavorable prognosis factor by multivariate analyses with Cox proportional hazard regression model. Kaplan–Meier curve showed that OSCC patients with an Ep-CAM LI < 50% had a significantly poorer cumulative survival than those with an Ep-CAM LI ≥ 50% ( P  < 0.00001, log-rank test).
Conclusions:  We conclude that the decreased expression of Ep-CAM protein is an early event in oral carcinogenesis. The Ep-CAM LI in OSCC samples can predict the progression of OSCCs and the survival of OSCC patients.     

Expression of hepatocyte growth factor and c-met protein is significantly associated with the progression of oral squamous cell carcinoma in Taiwan

BACKGROUND: Hepatocyte growth factor (HGF) is a pleotropic growth factor that regulates cell proliferation, migration, survival, tumor angiogenesis, and tumor cell invasion and metastasis. Its diverse biological effects are mediated through its interaction with its receptor, c-met protein. METHODS: In this study, we examined the expression of HGF and c-met protein in 93 specimens of oral squamous cell carcinoma (OSCC), 10 specimens of oral epithelial dysplasia (OED), 14 specimens of oral epithelial hyperkeratosis (OEH), and 16 specimens of normal oral mucosa (NOM) by immunohistochemistry. The HGF and c-met labeling indices (LIs) in OSCC, OED, OEH, and NOM groups were calculated and compared between groups. The correlation between the expression of HGF or c-met in OSCCs and clinicopathological parameters, or survival of OSCC patients was analyzed statistically to investigate the possible influence of HGF or c-met on the progression and prognosis of OSCCs in Taiwan. RESULTS: Positive HGF or c-met staining was mainly cytoplasmic. The mean HGF LI increased significantly from NOM (3.1 +/- 5.1%) through OEH (32.5 +/- 19.8%) and OED (52.0 +/- 19.3%) to OSCC (71.9 +/- 28.6%; P = 0.000). The mean c-met LI also increased significantly from NOM (25.8 +/- 30.8%) and OEH (34.4 +/- 19.3%) through OED (53.0 +/- 20.0%) to OSCC (73.0 +/- 29.4%; P = 0.000). Statistical analysis showed that the c-met LI in either the tumor center or invasion front was significantly associated with T status, N status, and clinical staging of OSCC. However, only the HGF LI in the tumor invasion front was significantly correlated with N status and clinical staging of OSCC. CONCLUSION: Our results suggest that the expression of HGF and c-met protein is an early event in oral carcinogenesis in Taiwan. The HGF LI in the tumor invasion front and the c-met LI in either the tumor center or invasion front can predict the progression of OSCCs in Taiwan.     

Fatty acid synthase expression in squamous cell carcinoma of the tongue: clinicopathological findings

Background:  Overexpression of fatty acid synthase (FAS), the cytosolic enzyme responsible for the conversion of dietary carbohydrates to fatty acids, has been reported in several human malignancies and pointed as a potential prognostic marker for some tumors. This study investigated whether FAS immunohistochemical expression is correlated with the clinicopathological characteristics of oral squamous cell carcinoma (OSCC).
Materials and methods:  The clinical features of 102 patients with OSCC of the tongue treated in a single institution were obtained from the medical records and all histopathological diagnoses were reviewed. The expression of FAS was determined by the standard immunoperoxidase technique in formalin-fixed and paraffin-embedded specimens and correlated with the clinicopathological characteristics of the tumors.
Results:  Eighty-one cases (79.41%) were positive for FAS. Microscopic characteristics such as histological grade ( P  < 0.05), lymphatic permeation ( P  < 0.001), perineural infiltration ( P  < 0.05), and nodal metastasis ( P  < 0.02) were associated with FAS status. A significantly lower survival probability for patients with advanced clinical stage (log-rank test, P  < 0.001), lymph nodes metastasis (log-rank test, P  < 0.001), presence of vascular permeation (log-rank test, P  = 0.05), and perineural invasion (log-rank test, P  = 0.01) was observed in the studied samples.
Conclusion:  The expression of FAS in OSCC of the tongue is associated with the microscopic characteristics that determine disease progression and prognosis.     

Activation of nuclear factor-kappa B correlates with tumor necrosis factor-alpha in oral lichen planus: a clinicopathologic study in atrophic-erosive and reticular form

Backgroud:  Nuclear factor-kappa B (NF-κB) is believed to be involved in the pathogenesis of various inflammatory diseases, including oral lichen planus (OLP). The objective of the present study was to investigate the possible relationship between NF-κB activation and expression of tumor necrosis factor-alpha (TNF-α) in OLP and their expression pattern in relation to several clinical features.
Methods:  Thirty OLP cases were divided into atrophic-erosive form (14 cases) and reticular form (16 cases) according to their clinical manifestations. The expression of NF-κB p65 and TNF-α of both two groups were investigated by immunohistochemical staining, and the percentage of positive cells was calculated in each case. Biopsies of 10 normal oral mucosa (NOM) also underwent the same procedure as controls.
Results:  Nuclear factor-kappa B p65 nuclear staining was found in nuclei of basal and suprabasal epithelial keratinocytes in OLP, however, no positive staining was found in NOM. Positive TNF-α staining was detected in cytoplasm of basal epithelial keratinocytes in OLP, and only scattered staining was detected in NOM. Expression of NF-κB p65 and TNF-α were significantly different with respect to clinical forms and lesion sites ( P  < 0.05), except for genders ( P  > 0.05) in 30 OLP cases. NF-κB nuclear staining positively correlated ( r  = 0.676, P  < 0.01) with TNF-α overexpression in OLP.
Conclusions:  Nuclear factor-kappa B activation and its correlation with overexpression of TNF-α may play an important role in pathogenesis of OLP. There might be a positive regulatory loop between NF-κB and TNF-α, which may contribute to inflammation in OLP; NF-κB may also protect epithelial keratinocytes from excessive apoptosis.     

Expression of CXCR4 in oral squamous cell carcinoma: correlations with clinicopathology and pivotal role of proliferation

J Oral Pathol Med (2010) 39 : 63–68
Background:  The chemokine SDF-1 and its receptor CXCR4 play active role in the metastasis and proliferation of several malignancies.
Methods:  In this study, we used an immunohistochemical technique in 91 specimens of oral squamous cell carcinoma (SCC), and flow cytometry technique in oral SCC cell line, and then evaluated the role of proliferation of CXCR4 using MTT assay in oral SCC cell line.
Results:  The expression of CXCR4 in 91 specimens of oral SCC was 62.6% and in oral SCC cell line was 68.6%. There was a significant association between the expression of CXCR4 and lymph node metastasis ( P  = 0.012), tumor size ( P  = 0.01), UICC stage ( P  = 0.016), tumor histology grade ( P  < 0.001). SDF-1 stimulated proliferation of oral SCC cell and CXCR4 neutralization by monoclonal antibodies decreased proliferation.
Conclusions:  Our results suggest that CXCR4 might be a novel biomarker to evaluate the biological behavior of oral SCC. CXCR4 inhibitors or antagonists might be potential anticancer agents to suppress tumor proliferation.     

The close association between dental and periodontal treatments and oral ulcer course in behcet's disease: a prospective clinical study

Objective:  The aim of the study was to evaluate the influence of dental and periodontal treatments to the course of oral ulcers in patients with Behcet's disease (BD).
Methods:  Fifty-eight consecutive BD patients with oral ulcers were studied. Twenty-nine patients were in the intervention group (F/M: 15/14, mean age: 39.6 ± 6.9 years) and 29 (F/M: 15/14, 39.4 ± 10.6 years) were followed with a conventional treatment approach. In addition to oral hygiene education, dental and periodontal treatments were carried out in the intervention group, whereas the control group was only given oral hygiene education. Patients were evaluated in the pre-treatment observation period (1 month), treatment period (1 month) and 6 months after treatment.
Results:  An increase in the number of new oral ulcers (4.1 ± 3.5) was observed within 2 days during the treatment compared with 3–30 days during treatment month (2.3 ± 1.2) ( P  = 0.002). However, 6 months after the treatment, the number of oral ulcers (1.9 ± 1.5) was significantly lower compared with the pre-treatment observation (4.8 ± 3.2) ( P  = 0.000) and treatment periods (6.4 ± 2.3) in the intervention group ( P  = 0.05), whereas a similar oral ulcer presence was observed in the control group (2.8 ± 2.4, 3.7 ± 2.3 and 4.8 ± 4.3, respectively) ( P  > 0.05). Dental and periodontal indices were also better in the intervention group during the 6-month follow-up.
Conclusion:  Our results suggest that, in BD patients, dental and periodontal therapies could be associated with a flare-up of oral ulcers in the short term, but may decrease their number in longer follow-up. They also lead to a better oral health.     

Shifts in cellular localization of moesin in normal oral epithelium, oral epithelial dysplasia, verrucous carcinoma and oral squamous cell carcinoma

BACKGROUND: Moesin, a member of ERM (ezrin/radixin/moesin) family, links actin filaments of cell surface structure to the cell membrane. The purpose of the study is to assess the shifts in cellular distribution of moesin in normal oral epithelium, oral epithelial dysplasia (OED), verrucous carcinoma (VC), and oral squamous cell carcinoma (OSCC). METHODS: The expression of moesin was evaluated immunohistochemically in paraffin-embedded tissues of 59 specimens of OSCC, 35 specimens of OED, 17 specimens of VC, and five specimens of normal oral epithelium. RESULTS: In the normal oral epithelia, all specimens showed a pattern of membranous expression against the anti-moesin antibody in the basal layer cells. In the OED specimens, moesin was dominantly expressed in the cell membrane except for the cornified layer. In VC and OSCC specimens, almost the whole of the carcinoma cells were stained with anti-moesin antibody. However, in OSCC samples, moesin was markedly expressed increasingly in the cytoplasm and decreasingly in the cell membrane, as compared with OED and VC. In addition, there was a significant correlation between the pattern of moesin expression and tumor differentiation in OSCC. CONCLUSIONS: Our results suggest that it is useful to detect the moesin expression as adjunct to screening mucosal lesions in the oral cavity.     

A composite index for determining the impact of oral ulcer activity in Behcet's disease and recurrent aphthous stomatitis

Background:  Although number, frequency and healing time of oral ulcers and pain are generally used for clinical practice and studies in Behcet's disease (BD) and recurrent aphthous stomatitis (RAS), no standardized activity index is currently present to monitor clinical manifestations associated with oral ulcers. The aim of this study was to develop a standardized composite index (CI) to assess oral ulcer activity in BD and RAS.
Methods:  In this cross-sectional study, 121 patients with BD and 45 patients with RAS were included. Sixty-five percentage of BD and 68.9% of RAS patients were in active stage during the previous 3 months. The developed CI included the presence of oral ulcers, ulcer-related pain and functional status and was evaluated in patients with both active and inactive disease for content validity.
Results:  Composite index score was observed to be higher in active patients with RAS (6.94 ± 2.19) compared with active BD patients (6.01 ± 2.04) ( P  = 0.04). The number of oral ulcers and healing time of oral ulcers were significantly higher in RAS compared with BD ( P  = 0.018, P  = 0.001 respectively). CI score correlated with the number of oral ulcers in both BD and RAS ( P  = 0.000, P  = 0.002 respectively). CI score was '0' for inactive patients without oral ulcer in BD and RAS.
Conclusions:  The presented CI as an oral ulcer activity index seems to be a reliable and suitable tool for evaluating the clinical impact and disease-specific problems in BD and RAS.     

K_v3.4在口腔扁平苔藓和口腔鳞状细胞癌中的表达

目的:研究钾离子通道蛋白kv3.4在正常口腔黏膜(normal oral mucosa,NOM)、口腔扁平苔藓(oral lichen planus,OLP)、口腔鳞状细胞癌(squamous cell carcinoma,OSCC)中的表达及意义。方法:免疫组织化学技术检测16例NOM、20例OLP和30例OSCC组织中kv3.4的表达,采用Wilcoxon秩和检验,α=0.05。结果:kv3.4在OSCC中的表达强度高于OLP(P<0.05),kv3.4在OLP组织的表达高于正常组织(P<0.05),且糜烂型OLP中的表达高于非糜烂型OLP(P<0.05),差异均具有统计学意义。结论:kv3.4可能与OLP及OSCC的发生、发展有一定的关系。     

Prognostic significance of Bcl-2 and Bax protein expression in the patients with oral squamous cell carcinoma

Background:  The aim of this study was to investigate the expression of the apoptosis-inhibitory Bcl-2 protein and the apoptosis-promoting Bax protein and to identify their association with the clinical parameters and prognosis of the patients with oral squamous cell carcinoma (OSCC).
Methods:  The expression of Bcl-2 and Bax proteins was evaluated by immunohistochemical staining in specimens from 110 patients with OSCC. Every section was scored according to both the percentage of positive staining tumor cells and the staining intensity. The Kaplan-Meier test and Cox proportional hazards regression analysis were performed to assess the correlation between the protein levels and the long survival rate of patients. The association between Bax, Bcl-2 immunoexpression and clinicopathologic variables was analyzed with the chi-square test and non-parametric analysis. The Bcl-2 and Bax immunoexpression in 20 oral mucosa samples were also investigated as normal control.
Results:  The results showed that the 5-year survival rate was significantly higher in the patients with the ratio of Bcl-2/Bax ≤ 1 than in those with Bcl-2/Bax > 1 (76.79 ± 6.69% vs. 59.26 ± 6.69%, P  = 0.0489). Bax immunoreactivity was significantly correlated with histological grading and lymph node metastasis. Univariate analysis indicated that the ratio of Bcl-2/Bax and lymph node metastasis were two independent factors related to the prognosis.
Conclusion:  The ratio of Bcl-2/Bax could be used as an effective biomarker to predict the prognosis of OSCC.     

Progressive increase of human papillomavirus carriage rates in potentially malignant and malignant oral disorders with increasing malignant potential

Introduction:  We investigated the potential role of human papillomaviruses (HPVs) in potentially malignant oral disorders, oral leukoplakia (OL) and oral lichen planus (OLP), and in oral squamous cell cancer (OSCC) in an Eastern Hungarian population with a high incidence of OSCC.
Methods:  Excised tumor samples (65 OSCC patients) and exfoliated cells from potentially malignant lesions (from 44 and 119 patients with OL and OLP, respectively) as well as from healthy controls (72 individuals) were analysed. OLPs were classified based on clinical appearance, 61 patients had erosive–atrophic lesions (associated with higher malignancy risk, EA-OLP) and 58 had non-erosive non-atrophic lesions (with lower risk of becoming malignant, non-EA-OLP), respectively. Exfoliated cells collected from apparently healthy mucosa accompanied each lesion sample. HPV was detected by MY/GP polymerase chain reaction (PCR) and genotyped by restriction analysis of amplimers. Copy numbers in lesions were determined using real-time PCR. Prevalence rates, copy number distributions, and association with risk factors and diseases were analysed using chi-square test, t -test, and logistic regression, respectively.
Results:  We detected HPVs significantly more frequently in lesions than in controls ( P  ≤ 0.001 in all comparisons). HPV prevalence increased gradually with increasing severity of lesions (32.8, 40.9, and 47.7% in OLP, OL, and OSCC, respectively). Copy number distribution patterns roughly corresponded to prevalence rates, but OLP and OL were comparable. HPV prevalence differed significantly between EA-OLP and non-EA-OLP groups (42.6 vs. 22.4%); EA-OLP group showed a prevalence similar to that found in OL.
Conclusion:  HPVs may be involved in the development or progression of not only OSCC but also of potentially malignant oral lesions.     

Treatment with levamisole and colchicine can result in a significant reduction of IL-6, IL-8 or TNF-α level in patients with mucocutaneous type of Behcet's disease

Background:  Mucocutaneous type of Behcet's disease (MCBD) is a multisystemic inflammatory disease with oral and genital ulcers with or without skin lesions.
Methods:  A solid phase, two-site sequential chemiluminescent immunometric assay was used to measure serum levels of interleukin (IL)-6, IL-8 and tumour necrosis factor (TNF)-α in 54 normal control subjects and in 64 MCBD patients before and after treatment with levamisole plus colchicine.
Results:  We found that 67%, 83% or 67% of MCBD patients had a serum IL-6, IL-8 or TNF-α level greater than the upper normal limit of 4.7, 8.7 or 7.4 pg/ml, respectively. The mean serum level of IL-6 (9.9 ± 2.4 pg/ml, P  < 0.005), IL-8 (107.5 ± 21.4 pg/ml, P  < 0.001) or TNF-α (22.5 ± 4.1 pg/ml, P  < 0.001) in 64 MCBD patients was significantly higher than that (2.1 ± 0.2, 5.7 ± 0.2 or 3.8 ± 0.2 pg/ml for IL-6, IL-8 or TNF-α level, respectively) in normal control subjects. In 43 MCBD patients with all the serum IL-6, IL-8 and TNF-α levels higher than their upper normal limits, treatment with levamisole plus colchicine for a period of 0.5–11.5 (mean, 3.2 ± 2.4) months could significantly reduce the mean serum IL-6, IL-8 and TNF-α levels from 9.0 ± 1.7 to 1.6 ± 0.2 pg/ml ( P  < 0.001), 134.6 ± 28.2–6.0 ± 0.4 pg/ml ( P  < 0.001) and 25.7 ± 5.6–3.5 ± 0.4 pg/ml ( P  < 0.001), respectively.
Conclusions:  Treatment with levamisole and colchicine can result in a significant reduction of serum IL-6, IL-8 or TNF-α level in MCBD patients.     

Expression of Mcm-2, Ki-67 and geminin in benign and malignant salivary gland tumours

Background:  Recent studies have proposed that minichromosome maintenance (Mcm) proteins may be sensitive proliferation markers and may serve as novel biomarkers for prognostication and diagnosis of various pre-malignant and malignant lesions. The aims of this study were to determine the expression of Mcm-2, Ki-67 and geminin in salivary gland (SG) tumours, and to evaluate their usefulness for diagnosis or for prediction of tumour behaviour.
Methods:  Tissue from 62 SG tumours was assembled in tissue microarray format. There were 13 adenoid cystic carcinomas (ACC), 10 carcinoma ex pleomorphic adenomas (CEPA), 10 mucoepidermoid carcinomas (MEC), 10 polymorphous low-grade adenocarcinomas (PLGA), 10 pleomorphic adenomas (PA) and nine acinic cell carcinomas (AcCC). Clinicopathological data were collected retrospectively and immunohistochemical analyses of Mcm-2, Ki-67 and geminin were performed on all lesions. Labelling index (LI) for each marker was determined by counting the percentage of positive cells in six random fields from three arrays per case.
Results:  Mcm-2 expression was higher than Ki-67 and geminin in all tumours studied. Mcm-2 LI was higher in ACC (28.2 ± 19.2%) than in CEPA, AcCC, MEC, PA and PLGA (5.3 ± 4.1%, P  = 0.001). Mcm-2 LI was higher in CEPA (20.4 ± 5.0%) than in PA (6.9 ± 5.0%, P  = 0.001). LI did not correlate to tumour grade or outcome for any of the markers or tumour types.
Conclusions:  The findings suggest that Mcm-2 may be a sensitive proliferation marker in SG tumours and may be useful for differential diagnosis between PA and CEPA, and ACC and PLGA. Further studies are warranted to assess the value of Mcm-2 as a predictor of recurrence and survival.     

CXCR-4 knockdown by small interfering RNA inhibits cell proliferation and invasion of oral squamous cell carcinoma cells

Background:  Oral squamous cell carcinomas (OSCCs) are characterized by a high degree of local invasion and a high rate of metastases to cervical lymph nodes. Downregulation of CXCR-4 by siRNA inhibits invasion and growth of breast and colon cancer cells. However, there have been no reports on the downregulation of CXCR-4 by small interfering RNA (siRNA) in oral cancer cells.
Methods:  We generated two stable CXCR-4-knockdown clones (KBsi and KOSCC-25Bsi) from the KB and KOSCC-25B OSCC cell lines by lentiviral delivery. In vitro invasion and cell proliferation assays were used to investigate the effect of CXCR-4 downregulation on cell proliferation and invasiveness in KBsi and KOSCC-25Bsi. Immunohistochemistry was performed to evaluate the correlation between CXCR-4 expression and proliferation in 26 OSCC tissue samples.
Results:  CXCR4-knockdown OSCC cells showed reduced invasiveness. The invasiveness of KBsi decreased to 29.5% of the vector-infected controls, and KOSCC-25Bsi decreased to 38.1% of the control vector-infected cells ( P  <   0.05). The CXCR4-knockdown OSCC cells grew significantly slower than the vector-infected control cells. KBsi and KOSCC-25Bsi cells proliferated at 69.5% and 71.7%, respectively, of the rate of control vector-infected cells ( P  <   0.05). CXCR-4-positive group had significantly higher PCNA labeling index than CXCR-4-negative group in OSCC tissue samples.
Conclusion:  These results suggest that the downregulation of CXCR-4 induces anti-proliferative and anti-invasive effects in OSCC and that CXCR-4 might be a useful target molecule for the treatment of OSCC.     

Expression of phosphorylated Akt in oral carcinogenesis and its induction by nicotine and alkaline stimulation

Background:  In Taiwan, it is well documented that cigarette smoking and areca nut chewing contribute to the risk of oral squamous cell carcinoma (OSCC). The role of phosphorylated Akt (p-Akt) in oral carcinogenesis induced by nicotine and alkaline environments was investigated.
Method:  Immunohistochemistry (IHC) was used to detect p-Akt expression in cancerous ( n  = 30) precancerous ( n  = 30), and normal mucosa tissues ( n  = 10). Western blotting was used to detect time-dependent induction of p-Akt by 100 μM nicotine in normal human bronchial epithelial cell (NHBE), normal human oral keratinocytes (NHOK), immortalized human epithelial cells (HaCaT) and OEC-M1 cells, dose-dependent induction of p-Akt in OEC-M1 and HaCaT cells and pH effect of p-Akt in OEC-M1. The unpaired t -test and the Fisher's exact test were used to analyze the p-Akt immunoreactivity in various groups and its association with clinicopathological parameters.
Results:  Higher p-Akt expression in cancerous group than in normal mucosa ( P  = 0.0002) and precancerous ( P  = 0.0049) groups was observed. A time-dependent increase in p-Akt in the NHBE, NHOK, HaCaT and OEC-M1 cell lines was observed with 100 μM nicotine treatment. The dose-dependent increase in p-Akt by nicotine treatment in HaCaT and OEC-M1 cells was obviously observed. Higher p-Akt expression in more alkaline environment (pH 8.0) was observed than at pH 7.4 in OEC-M1 cells.
Conclusion:  A potential role for increased p-Akt may relate to the dose and time of nicotine use. The potential role of an alkaline environment to enhance nicotine-related oral carcinogenesis may exist.     

Loss of human β-defensin 1, 2, and 3 expression in oral squamous cell carcinoma

Introduction:  Human β-defensins (HBDs) are cationic, antimicrobial peptides produced by epithelial cells and involved in various aspects of the innate and acquired immune responses. They are expressed by oral tissues as constitutive and inducible genes. Recently, single nucleotide polymorphisms (SNPs) of β-defensins have been correlated with increased susceptibility to certain diseases. Studies have reported altered expression of β-defensins in cancers suggesting their involvement in carcinogenesis. The purpose of this study was to evaluate the regulation of HBD-1 (also published as DEFB1), HBD-2 (DEFB4) and HBD-3 (DEFB103A) ( http://www.genenames.org/index.html ) and HBD-1 SNPs in oral squamous cell carcinoma cell lines (OSCC) and healthy gingival keratinocytes.
Methods:  β-defensin expression was quantitatively assessed using real-time polymerase chain reactions in OSCC and control cell lines after exposure to interleukin-1β, tumor necrosis factor-α, and interferon-γ. Control data were obtained in a previous study. DNA from 19 OSCC cell lines and 44 control subjects were extracted and the HBD-1 region spanning the 5' untranslated region to the first intron was sequenced and analysed for SNP identification and distribution.
Results:  HBD-1 and HBD-2 basal messenger RNA expression were significantly lower in OSCC. In addition, the ability to be induced was significantly reduced in OSCC for all three β-defensins. Four HBD-1 SNPs were differentially distributed between cancer and control populations. Genotype distribution at the HBD-1 locus also suggested loss of heterozygosity in OSCC.
Conclusions:  The genetic variation observed in OSCC compared with that in control cell lines may account for differences in β-defensin expression. These results suggest a putative role for β-defensins in carcinogenesis and indicate that β-defensins may be useful markers of OSCC.     

Metallothionein and p-Akt proteins in oral dysplasia and in oral squamous cell carcinoma: an immunohistochemical study

Background:  Oral leukoplakia (OL) is the main potentially malignant lesion of the oral cavity, and oral squamous cell carcinoma (OSCC) accounts for more than 95% of all malignant neoplasms in the oral cavity. Therefore, the aim of this study was to verify the immunoexpression of p-Akt and Metallothionein (MT) proteins in dysplasic and neoplasic oral lesions.
Methods:  Immunohistochemical studies were carried out on 10 normal epithelium, 30 OL and 15 OSCC paraffin-embedded samples. Immunoperoxidase reaction for p-Akt and MT proteins was applied on the specimens, and the positivity of the reactions was calculated for 1000 epithelial cells.
Results:  Using the ANOVA and the Tukey's post hoc statistical analyses, it was observed a significant difference in the immunoexpression for p-Akt and MT when the OSCC samples were compared with normal and dysplasic epithelial groups. In addition, the Pearson's correlation test showed a significant correlation between the proteins' expression.
Conclusion:  Based on the data obtained, p-Akt and MT activation may play an important role in the conversion of a potentially malignant oral lesion to a malignant carcinoma since its earlier stages.