Eosinophils may predict occult lymph node metastasis in early oral cancer

Objective

The aim of this study was to investigate whether tumor-associated tissue eosinophilia (TATE) in early oral squamous cell carcinoma (OSCC) would aid in predicting occult lymph node metastasis.

Patients and methods

Seventy-one patients undergoing elective neck dissection for T1 and T2 OSCC were evaluated for clinical features, prognosis, and TATE. The degree of TATE in OSCC was statistically analyzed in relation to the clinicopathological features, tumor invasion, occult lymph node metastasis, and survival using χ ² test and Kaplan–Meier method.

Results

Statistical analysis revealed that intense TATE was a significant feature (p?=?0.004) to predict occult lymph node metastasis in patients with early OSCC. All regional recurrences of the OSCC occurred in patients showing intense TATE.

Conclusions

These results suggest that intense TATE can be clinically used as a predictive factor for occult lymph node metastasis.

Clinical relevance

The presence of intense TATE is an adjunctive histopathological marker to reinforce the indication of elective neck dissection of the patients with early OSCC.     

P21/ WAF1 and cyclin D1 variants and oral squamous cell carcinoma

Background:  Genetic factors are known to be involved in oral squamous cell carcinoma (OSCC) development.
Method:  We evaluated a possible association between CCND1 A870G and P21/WAF1 C98A polymorphisms and OSCC, as well as the impact of the genotypes on protein immunoexpression. The study group consisted of 80 individuals with histopathological diagnosis of OSCC and the control group consisted of 80 healthy individuals without oral lesions and matched by age, sex and tobacco usage. The genotypes were studied by the polymerase chain reaction and restriction fragment length polymorphic analysis. Paraffin-embedded sections were used for immunohistochemical analysis.
Results:  No statistical association between CCND1 and/or P21/WAF1 genotypes and OSCC was demonstrated, although we found that people harbouring the combined presence of at least one variant allele of both genes showed a 1.8 times more chance of developing OSCC compared to the referent genotype. OSCC tumours from individuals with P21 heterozygous genotype showed a significantly higher immunopositivity than tumours from wild-type individuals.
Conclusion:  The present study did not demonstrate a significant association between CCND1 and / or P21 / WAF1 genotypes and OSCC. However, P21 protein expression in OSCC tumours is affected by P21 / WAF1 genotype.     

Role of TP53 in the progression of pre-malignant and malignant oral mucosal lesions. A follow-up study of 144 patients

Background:  Prediction of progression from pre-malignant oral mucosal lesions to malignancy, or recurrence of an existing oral squamous cell carcinoma (OSCC), is an important clinical problem in oral medicine.
Methods:  This study presents a follow-up of a study published in 2002. Samples from 54 patients with OSCC, 45 with oral lichen planus (OLP) and 45 with hyperkeratosis (clinically leukoplakia), diagnosed between 1987 and 1996, were analysed for TP53 protein expression and TP53 mutation. Follow-up was 11–17 years for OSCC (mean 13.3), 12–22 years for OLP (mean 15.9) and 12–17 years for hyperkeratosis (mean 14.5).
Results:  Of the 54 OSCC patients, 28 experienced recurrent disease, 21 died of OSCC, 22 died of other causes. Of the 14 OSCC patients with mutated TP53 ( n  = 11), the cancer recurred in eight (57%) and in 20/39 (51%) without mutation. Expression of TP53 protein was significantly associated with reduced overall survival. Among OLP patients, nine were TP53- mutated out of 31 tested. One TP53- mutated OLP patient developed OSCC in a different site. Of the hyperkeratosis patients, three were mutated of 22 tested. One hyperkeratosis patient (non-mutated) developed OSCC in the same site.
Conclusion:  TP53 mutations can exist in benign oral mucosal lesions for many years without progression to malignancy. No association was found between TP53 protein expression or TP53 mutation and recurrence of OSCC or disease-related survival. Overall survival was reduced in patients with positive TP53 protein expression.     

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.     

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.     

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.     

Expression of hypoxia-inducible factor-1α is significantly associated with the progression and prognosis of oral squamous cell carcinomas in Taiwan

Background:  Overexpression of hypoxia-inducible factor-1α (HIF-1α) has been found to be significantly associated with the tumor invasion, lymph node metastasis, clinical stage, and prognosis of a variety of human cancers.
Methods:  This study examined the expression of HIF-1α in 57 specimens of oral squamous cell carcinoma (OSCC), 41 specimens of oral epithelial dysplasia (OED, 12 mild, 17 moderate, and 12 severe OED cases), and 14 specimens of normal oral mucosa (NOM) by immunohistochemistry.
Results:  We found that the mean nuclear HIF-1α labeling indices (LIs) increased significantly from NOM (9 ± 6%) through mild OED (25 ± 18%), moderate OED (41 ± 27%), and severe OED (42 ± 22%) to OSCC samples (55 ± 23%, P  < 0.001). A significant correlation was found between the higher mean nuclear HIF-1α LI and OSCCs with larger tumor size ( P  < 0.001), regional lymph node metastasis ( P  < 0.001), or more advanced clinical stages ( P  < 0.001). Only larger tumor size ( P  = 0.002) and nuclear HIF-1α LI ≥ 60% ( P  = 0.048) were identified as independent unfavorable prognosis factor by multivariate analyses with Cox regression model. Kaplan–Meier curve showed that OSCC patients with a nuclear HIF-1α LI ≥ 60% had a significantly poorer cumulative survival than those with a nuclear HIF-1α LI < 60% (log-rank test, P  = 0.022).
Conclusions:  We conclude that the expression of HIF-1α is an early event in oral carcinogenesis. The nuclear HIF-1α LI in OSCC samples can predict the progression of OSCCs and the survival of OSCC patients.     

Eotaxin expression in oral squamous cell carcinomas with and without tumour associated tissue eosinophilia

AIM: Eotaxin is a powerful and selective eosinophil chemoattractant. The purpose of this study was to compare the expression of eotaxin in oral squamous cell carcinomas with and without tumour associated tissue eosinophilia (TATE). The mechanisms that control the recruitment of eosinophils to these tumours are not clearly established. METHODS: A total of 60 patients with oral squamous cell carcinomas (OSCC) with TNM stages II and III, located in the tongue, oral floor, retromolar area and inferior gingiva were divided in two groups: 1--OSCC with intense eosinophilic inflammatory infiltrate and 2--OSCC with absent/low eosinophilic inflammatory infiltrate. The eotaxin expression was analyzed by immunohistochemistry using standard streptavidin-biotin-peroxidase complex technique with monoclonal (mouse anti-human eotaxin) and polyclonal (rabbit anti-human eotaxin) antibodies. RESULTS: The eotaxin expression was identified in normal oral mucosa as well as in both OSCC groups including malignant epithelial cells, eosinophils, neutrophils, plasma cells and fibroblasts. The eosinophils showed intense immunopositivity for eotaxin. CONCLUSION: These results suggest that the eotaxin expressed in oral squamous cell carcinomas, mainly derived from eosinophils, is probably involved in the mechanisms of eosinophils chemotaxis to the tumour and in the maintenance of TATE in these malignant tumours.     

Overexpression of cytokeratin 17 protein in oral squamous cell carcinoma in vitro and in vivo

Objective:  To determine the cytokeratin 17 (CK17) expression in oral squamous cell carcinoma (OSCC) both in vitro and in vivo .
Methods:  Comparative proteomic analysis of an in vitro cellular carcinogenesis model of OSCC (including a line of human immortalized oral epithelia cells (HIOECs), a line of cancerous HB96 cells and another kind of cells (HB56 cells) at the early stage of carcinogenesis was performed to identify differentially expressed proteins. CK17 was further validated in vitro (cellular carcinogenesis model and other three OSCC lines) and in vivo (tissues from six healthy persons and 30 primary OSCC patients) by Western blotting and immunohistochemistry respectively.
Results:  Increased CK17 expression was identified by two-dimensional gel electrophoresis and liquid chromatography–tandem mass chromatography in the HB56 and HB96 cells over HIOECs. Western blotting confirmed the increased CK17 expression in the HB56, HB96 cells and other three OSCC lines. Immunohistochemistry confirmed the increased CK17 expression in the cancerous tissues from OSCC patients compared with the paired adjacent non-malignant epithelia.
Conclusion:  Increased CK17 expression may play an important role in the carcinogenesis progression of OSCC; however, further studies on the molecular function of CK17 are encouraged to clear the precise mechanism of CK17 in OSCC.     

Functional variants of IL4 and IL6 genes and risk of tobacco-related oral carcinoma in high-risk Asian Indians

Oral Diseases (2011) 17 , 720–726 Background: Tobacco‐related oral squamous cell carcinoma (OSCC) is one of the most common cancers involving Indian males. We assessed the association of IL4 promoter –589 T>C, –33 T>C, and IL6–174 G>C functional genetic polymorphisms with tobacco‐related OSCC in Asian Indians. Patients and Methods: The IL4 and IL6 promoter polymorphisms were assessed in 140 patients with OSCC and 120 normal subjects by PCR–RFLP technique, and significance of the data was determined using chi‐square test. Results: The frequency of TC, CC genotype, and C allele at IL4 promoter sites –589 and –33 were higher in patients when compared with controls. Consequently, TC/CC genotypes and C allele at both sites appeared as susceptible. However, IL6–174 G>C single‐nucleotide polymorphisms (SNP) appeared to be protective in patients with OSCC. Of eight haplotypes, five were associated with two‐ to seven‐fold increased risk of tobacco‐related OSCC. These SNPs further showed heterogeneity among different ethnic population, but their distribution in Asian Indians stand closer to other Asian populations. Conclusions: In this study, IL4–589 CC, –33 CC genotype, and *C allele at both sites appeared to be susceptible, while IL6–174 CC genotype and *C allele appeared to be protective in patients with OSCC; hence, these SNPs may be a potential prognostic markers for tobacco‐related OSCC in Asian Indians.     

Association of vitamin D receptor gene polymorphisms in Chinese patients with generalized aggressive periodontitis

Background and Objective:  The clinical features suggest that genetic factors may have a strong influence on susceptibility to aggressive periodontitis. The aim of this study was to investigate the association of vitamin D receptor gene polymorphisms with generalized aggressive periodontitis in Chinese patients.
Material and Methods:  A restriction fragment length polymorphism (RFLP) for 10,438,141 C to T (rs1544410, Bsm I), 10,382,063 A to G (rs731236, Taq I), 10,382,143 C to A (rs7975232, Apa I) and 10,416,201 A to G (rs2228570, Fok I) of vitamin D receptor gene was analysed by polymerase chain reaction, followed by digestion with restriction enzymes and gel electrophoresis. The genotypes of 51 generalized aggressive periodontitis patients and 53 periodontally healthy control subjects were analysed. The genotypic and allelic frequencies of each polymorphism site for the patients and control subjects were compared.
Results:  The distribution of vitamin D receptor Fok I genotypes and alleles between the two groups was significantly different ( p =  0.043 and p  = 0.012, respectively). The F allele seemed to increase the susceptibility of aggressive periodontitis (odds ratio = 2.02, 95% confidence interval = 1.16–3.50) in Chinese patients. There was no significant difference in the genotype distribution or the allele frequencies of vitamin D receptor Bsm I, Apa I and Taq I between two groups.
Conclusion:  The study indicates that Fok I polymorphism of vitamin D receptor gene might be associated with generalized aggressive periodontitis in Chinese patients. In addition, the carriage of F allele increases the risk of developing generalized aggressive periodontitis.     

Oxidant–antioxidant status in blood and tumor tissue of oral squamous cell carcinoma patients

Background and Objective:  Increased oxidative and nitrosative stress associated with disturbances in antioxidant defense system have been implicated in the pathogenesis of several diseases, most notably oral cancer. The aim of this study was to evaluate the oxidant–antioxidant status in blood samples and tumor tissue in oral squamous cell carcinoma (OSCC) patients in comparison with the healthy controls.
Methods:  Blood and tumor tissue samples from the diseased individuals and the normal controls were analyzed for malondialdehyde (MDA) and nitric oxide (NO) as indicators of oxidative stress and nitrosative stress respectively; superoxide dismutase (SOD) and catalase enzymes as indicators of antioxidant defense by UV visible spectrophotometer.
Results:  Malondialdehyde and NO levels were significantly elevated in the blood and tissue samples of OSCC patients as compared with the healthy controls. The antioxidant enzymes SOD and catalase were significantly reduced in tissue samples of OSCC group than in the control group while in the erythrocytes, catalase levels were significantly reduced and the SOD levels were higher in OSCC group in comparison with the healthy controls.
Interpretation and Conclusion:  Increased levels of MDA and NO indicate an increase in the oxidative stress in OSCC patients associated with a deficient antioxidant defense mechanism. This oxidant–antioxidant imbalance may be considered as one of the factors responsible for pathogenesis of cancer. Future studies regarding assessment of oxidant–antioxidant status in OSCC patients in view of selecting appropriate mode of therapy and the effectiveness of such therapy in limiting the tumor progression and recurrence is to be carried out.     

Serum soluble CD44v6 levels in patients with oral and maxillofacial malignancy

Objective:  To determine the levels of serum sCD44v6 in patients with oral cancer and evaluate the value of serum sCD44v6 in adjuvant diagnosis, staging and monitoring treatment response in these patients.
Materials and Methods:  A total of 112 hospitalized patients with oral and maxillofacial malignancy and 28 healthy individuals were examined for serum sCD44v6 levels. Venous blood was collected from these patients and the healthy individuals. One week after treatment, venous blood was collected once again in 60 patients with oral and maxillofacial squamous cell carcinoma (OSCC).
Results:  The sCD44v6 concentration was not significantly different between patients with oral and maxillofacial malignancy and control group ( P  > 0.05). The levels of serum sCD44v6 in patients with OSCC and salivary carcinoma showed no difference with those in control group ( P  > 0.05). The sCD44v6 level in patients with stage III and IV disease was higher than that of patients with stage I and II and that of the control group, but the difference was not significant ( P  > 0.05).  Serum sCD44v6 levels in patients with OSCC after treatment became lower than that prevailed during pretreatment ( P  < 0.05).
Conclusion:  The possible roles of CD44v6 in the diagnosis of oral and maxillofacial malignancy deserve further elucidation and evaluation. Serum sCD44v6 may be a valuable marker in monitoring treatment response in patients with 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.     

Effects of small interfering RNAs targeting Fascin on gene expression in oral cancer cells

Background:  Oral squamous cell carcinoma (OSCC) is one of the most common head and neck cancers. The prognosis of OSCC is usually poor because of extensive local invasion at initial diagnosis. In the literature, Fascin has been reported responsible for cell motility and over-expression of Fascin contributes to an unfavorable clinical course. Nevertheless, the roles of Fascin protein playing in aggressiveness of OSCC and their potential mechanisms need to be elucidated.
Methods:  Two cell lines of OSCC (OECM-1 and SCC-25) via the vector-based small interfering RNA (siRNA) to suppress the expression of the Fascin gene were used. Subsequent analyses and observation regarding the expression of Fascin protein and cyto-morphological alterations were detected by Western blot and immunofluorescent microscopy. Boyden chamber invasion assay, cell migration assay and adhesion assay were also applied to investigate the functional changes of OSCC.
Results:  There were statistically significant differences ( P  < 0.05) of Fascin expression before and after silencing. Down-regulation of Fascin protein directly led to changes of cell surface protrusions under immunofluorescent microscopy and resulted in suppression of migration, invasion and increase of adhesion in both cell lines ( P  < 0.05). Furthermore, down-regulation of Fascin expression also resulted in alterations of E-cadherin, β-catenin and TWIST at certain level, implicative of an association with epithelial-mesenchymal transition (EMT).
Conclusions:  Our results suggest that expression of Fascin protein may play an essential role in regulation of progression of OSCC and contributes to the event of EMT in the early aggressiveness of OSCC.     

Cyclooxygenase-2-765G>C functional promoter polymorphism and its association with oral squamous cell carcinoma

Aim: Cyclooxygenase‐2 is a key enzyme in the conversion of arachidonic acid to prostaglandins, and has critical role in the progression of several malignancies, including oral squamous cell carcinoma. Methods: We designed a case‐control study to evaluate the susceptibility of the functional ?765G>C genetic variation in oral squamous cell carcinoma patients. Polymerase chain reaction‐based restriction fragment length polymorphism analysis was used to determine the polymorphism in oral squamous cell carcinoma (n = 150) patients and healthy controls (n = 150). Results: The genotype frequencies of cyclooxygenase‐2 765G>G, 765G>C, and 765C>C were 73.3%, 18.66%, and 8.0% in the cancer patients, and 94.66%, 4% and 1.3% in the controls, respectively. The cyclooxygenase‐2 GC and CC genotypes were significantly associated (P = 0.0003 and P = 0.01, respectively) with oral squamous cell carcinoma patients, when compared to the controls. The 765G>C genotypes were statistically significant, with habitual tobacco chewing and alcohol consumption + smoking (P = 0.05). Conclusions: This study highlights the genetic variant that might play a role in mediating susceptibility to oral squamous cell carcinoma in this population.     

Promoter hypermethylation of mismatch repair genes, hMLH1 and hMSH2 in oral squamous cell carcinoma

Objectives:  Major risk factors of oral squamous cell carcinoma (OSCC) are environmental and can lead to DNA mutagenesis. Mismatch repair (MMR) system functions to repair small DNA lesions, which can be targeted for promoter hypermethylation. We therefore wanted to test whether hypermethylation of MMR genes ( hMLH1, hMSH2 ) could contribute to oral carcinogenesis by correlating the information to patient clinical data.
Methods:  Genomic DNA was extracted from 28 OSCC and six normal oral epithelium samples. The methylation status of the two MMR genes was assessed using Methylation Specific PCR after DNA modification with sodium bisulfite. Serial sections of the same tissues were immunostained with antibodies against hMLH1 and hMSH2 protein.
Results:  Promoter hypermethylation was observed in 14/28 OSCC cases. Remarkably, 100% of patients with multiple oral malignancies showed hypermethylation in hMLH1 or hMSH2 compared with 31.5% of single tumor patients. In 10 cancer cases, expression of the hMLH1 and hMSH2 genes by immunostaining showed reduced or absence of expression of one of the genes, although some did not reflect the methylation status.
Conclusions:  Hypermethylation of hMLH1 and hMSH2 might play a role in oral carcinogenesis and may be correlated with a tendency to develop multiple oral malignancies.     

Apoptosis-associated markers and clinical outcome in human oral squamous cell carcinomas

Background:  Apoptosis is a genetically regulated cell death involved in the deletion of cells in normal or malignant tissues. Proteins of the Bcl-2 family play a key role in the control of apoptosis and carry out both pro-apoptotic and anti-apoptotic functions. The present study evaluated the prognostic value of Bcl-2 and Bax expression at the invasive front of oral squamous cell carcinoma (OSCC), taking clinicopathological findings into account.
Methods:  Fifty-six specimens of OSCC were randomly selected, and Bcl-2 and Bax expression was evaluated by immunohistochemistry in formalin-fixed, paraffin-embedded pre-treated specimens at the invasive front of OSCC. Clinicopathological data were gathered and patient survival was analysed.
Results:  No significant relationship was found between Bcl-2 or Bax expression and clinical variables. Patients with Bcl-2 expression had a worse prognosis than those without Bcl-2 expression, but the difference did not reach statistical significance. Patients with Bax expression had a significantly better prognosis than those without Bax expression ( P  <   0.05). In univariate analyses, T category, mode of cancer invasion and Bax expression showed significant correlations. Multivariate analysis revealed that the mode of cancer invasion and Bax expression were significant and independent variables. Bax expression was found to be the strongest independent prognostic parameter. Patients with negative Bcl-2 expression and positive Bax expression had a significantly better prognosis ( P  <   0.005).
Conclusion:  We suggest that Bax expression at the invasive front of OSCC is a significant predictor of prognosis and that it is therefore important to investigate the expression of Bcl-2 and Bax in this disease.