Alteration in the expression of cdk4 and cdk6 proteins in oral cancer and premalignant lesions

J Oral Pathol Med (2010) 39 : 793–799 Background: Cdk4 and cdk6, key players in G1 phase, have been shown to play an important role in the development of oral squamous cell carcinoma (OSCC). This study investigated the expression of these two proteins in OSCC and premalignant lesions including oral leukoplakia (OL) with and without dysplasia and determined if alterations in the expression of these two proteins could be used as markers of malignant transformation. Methods: Expressions of cdk4 and cdk6 were evaluated in 61 samples including OSCC, OL with and without dysplasia and normal oral mucosa using immunohistochemistry method. Nuclear staining of the keratinocytes was considered positive and the percentage of positive cells was calculated. Results: Expression of cdk4 was found in 11/15 (73.33%) OSCC, 13/14 (92.85%) OL with dysplasia, 13/20 (65%) OL without dysplasia and 3/12 (25%) normal mucosa. Expression of cdk6 was detected in 9/15 (60%) OSCC, 3/14 (21.43%) OL with dysplasia, 5/20 (25%) OL without dysplasia and 1/12 (8.33%) normal mucosa. In cdk4 stained specimens, the frequency of positive cases and the percentage of positive cells in normal mucosa was significantly lower than OL with dysplasia and OSCC. For cdk6 staining, the prevalence of positive cases and the percentage of positive cells in normal mucosa were significantly lower than OSCC. Conclusions: Overexpressions of cdk4 and cdk6 were observed in OSCC, indicating that these two proteins play a crucial role in OSCC. The aberrant expression of cdk4 was found in OL with dysplasia, suggesting that cdk4 may be involved in the early event of carcinogenesis.     

E‐cadherin downregulation and Twist overexpression since early stages of oral carcinogenesis

There is some evidence of Twist participation in oral carcinogenesis; however, little is known about its interaction with E‐cadherin in oral squamous cell carcinoma (OSCC) development. This experimental study included an immunohistochemical analysis of Twist and E‐cadherin proteins in paraffin‐embedded specimens of oral leukoplakia (OL), OSCC, and normal oral mucosa. In addition, it was also performed a Western blot and double‐immunofluorescence analysis of Twist and E‐cadherin expression in OSCC cell lines. Significant differences in Twist and E‐cadherin immunoexpression were observed between normal oral mucosa and OL, with an inverse relation since the earliest stages of oral dysplasia (r = ?0,512; P < 0.001). Western blot and double‐immunofluorescence analysis showed differences in Twist and E‐cadherin expression among human oral keratinocytes and OSCC cell lines suggesting that downregulation of E‐cadherin occurs in a dependent manner of Twist in OSCC. Our results showed a possible value of Twist and E‐cadherin in the prediction of risk of oral epithelium malignant transformation.     

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.     

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.     

诱导型一氧化氮合酶表达在口腔癌前病变口腔鳞癌发展过程中的作用研究

目的　探讨诱导型一氧化氮合酶 (iNOS)在口腔癌前病变、口腔鳞癌发展过程中的表达情况及其作用。方法　采用免疫组化SABC法检测 10例正常口腔黏膜、8例上皮单纯增生、2 0例上皮异常增生和 3 2例鳞状细胞癌组织中iNOS的表达。结果　正常口腔黏膜iNOS阴性表达 ;上皮异常增生组和鳞癌组中iNOS的表达较上皮单纯增生组均显著增加 (P <0 .0 5 ) ;随着上皮异常增生程度的加重 ,iNOS的标记指数逐级显著上升 (P <0 .0 5 ) ;上皮异常增生组与鳞癌组之间以及鳞癌的各病理分级之间iNOS的表达均无显著性差异 (P >0 .0 5 )。结论　iNOS的表达可能参与了口腔鳞癌的衍进过程     

Expression of p53 in oral mucosal hyperplasia, dysplasia and squamous cell carcinoma

OBJECTIVE: To assess p53 expression in a range of oral mucosal lesions and to relate the results to the clinical outcome in patients with dysplastic oral mucosal lesions and oral squamous cell carcinomas (OSCC).
MATERIALS AND METHODS: Archival tissue was available for eight cases of normal oral mucosa, 50 cases of oral mucosal hyperplasia, 41 cases of oral mucosal dysplasia and 48 cases of OSCC. The monoclonal antibody DO-7, reactive to p53 protein, was applied to paraffin-embedded sections using microwave pretreatment and immu-nohistochemical techniques.
RESULTS: The results showed that normal oral mucosa did not express p53.Positive nuclear staining was found in 18/50 (36%) cases of hyperplasia, 35/41 (85%) cases of dysplasia and 45/48 (94%) cases of OSCC.None of the p53 negative dysplasias progressed, while 19% of p53 positive cases of dysplasia recurred following excision and 11% of the cases underwent neoplastic transformation. Five out of 10 (50%) cases of severe dysplasia which were p53 positive resolved.
CONCLUSION: The proportion of cases with positive p53 expression increased from hyperplasia to dysplasia to OSCC. These results may indicate an involvement of p53 in neoplastic transformation as well as in proliferative events although the presence or absence of p53 staining could not be used to predict the outcome of potentially malignant oral mucosal lesions.     

RNA from brush oral cytology to measure squamous cell carcinoma gene expression

Background:  RNA expression analysis of oral keratinocytes can be used to detect early stages of disease such as oral cancer or to monitor on-going treatment responses of the same or other oral diseases. A limitation is the inability to obtain high quality RNA from oral tissue without using biopsies. While oral cytology cell samples can be obtained from patients in a minimally invasive manner they have not been validated for quantitative analysis of RNA expression.
Methods:  As a starting point in the analysis of tumor markers in oral squamous cell carcinoma (OSCC), we examined RNA in brush cytology samples from hamsters treated with dibenzo[a,l]pyrene to induce oral carcinoma. Three separate samples from each animal were assessed for expression of candidate marker genes and control genes measured with real-time RT-PCR.
Results:  Brush oral cytology samples from normal mucosa were shown to consist almost exclusively of epithelial cells. Remarkably, ß-2 microglobulin and cytochrome p450, 1B1 (CYP1B1) RNA showed potential utility as markers of OSCC in samples obtained in this rapid and non-surgical manner.
Conclusion:  Brush oral cytology may prove useful as a source of RNA for gene expression analysis during the progression of diseases of the oral epithelium such as OSCC.     

p16,p53,Ki67在口腔癌前病变表达及4年临床随访

目的 :研究 p16,p5 3 ,Ki-67蛋白表达与口腔癌前病变的关系。 方法 :采用免疫组织化学LsAB法对43例上皮异常增生 ( 2 0例轻度上皮异常增生 ,2 3例重度上皮异常增生 )和 2 0例正常口腔黏膜 p16,P5 3和Ki -67蛋白的表达进行研究 ,并对上皮异常增生患者实际癌变率做了 4年追踪。结果 :正常黏膜组 ,p5 3不表达 ,Ki -67少量表达 ,p16的阳性表达为 10 0 %。轻度上皮异常增生 ,p5 3 ,Ki-67少数表达 ,p16表达率为 86.96%。重度上皮异常增生 ,p5 3和Ki-67过度表达 ,p16表达明显下降 ,与正常黏膜 ,轻度上皮异常增生相比差异显著 (P <0 .0 5 )。p5 3和Ki-67蛋白过度表达而 p16呈低表达与实际口腔癌前病变癌变率有一定相关性。 结论 :口腔黏膜癌变是一个由量变到质变的过程 ,它们的调控基因 p16,p5 3 ,Ki -6发生了显著的变化 ,可能起着重要的调控作用。     

口腔白斑和鳞癌中p16基因甲基化的研究

目的　探讨p16基因甲基化在口腔黏膜白斑癌变中的作用。方法　采用甲基特异性PCR技术检测了 10例正常口腔黏膜、20例白斑上皮单纯增生、11例白斑上皮轻度异常增生、10例白斑上皮中度异常增生、9例白斑上皮重度异常增生、10例鳞癌Ⅰ级、12例鳞癌Ⅱ级、8例鳞癌Ⅲ级标本的p16基因甲基化情况。结果　上述各组的p16基因甲基化率分别为 0、5%、18%、10%、22%、50%、42%和 63%。p16基因甲基化率与口腔黏膜组织恶性度显著正相关,并与p16蛋白缺失表达率呈显著正相关关系(rp=0 777 , rs=0 960, P<0 001)。结论　p16基因甲基化状态可作为白斑癌变和口腔鳞癌诊断的分子生物学重要标志之一。     

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.     

Evaluation of myofibroblasts in oral epithelial dysplasia and squamous cell carcinoma

Background:  Carcinogenesis is accompanied by a number of changes in the adjacent stroma including the appearance of myofibroblasts. The purpose of this study was to evaluate and compare the presence of myofibroblasts in normal mucosa, oral epithelial dysplasia, and different grades of oral squamous cell carcinoma.
Methods:  The study sample consisted of three groups, including 40 oral squamous cell carcinomas, 15 dysplasias, and 15 sections of normal oral epithelium. Vimentin, desmin, and alpha-smooth muscle actin were used to identify myofibroblasts.
Results:  The percentage and intensity of alpha-smooth muscle actin were examined, and positive immunostaining was observed in the myofibroblasts of all squamous cell carcinomas; however these cells did not stain in the dysplasias or normal epithelium specimens. The presence of myofibroblasts was significantly higher in oral squamous cell carcinomas compared to both, dysplasias and normal mucosa cases ( P  < 0.001). A significant difference was not observed between the different grades of oral squamous cell carcinoma ( P  = 0.2).
Conclusions:  These findings show the presence of myofibroblasts in the stroma of oral squamous cell carcinoma but not dysplasia and normal mucosa, suggesting further investigation to clarify the role of myofibroblasts in the carcinogenesis of this tumor.     

Detection of survivin mRNA in healthy oral mucosa, oral leucoplakia and oral cancer

Background:  Survivin is involved in modulation of cell death and cell division processes. Survivin expression in normal adult tissues has not been fully understood, although it is markedly lower than in cancer, where it is over-expressed.
Objective:  To investigate survivin expression in normal, potentially malignant and cancerous oral mucosa.
Methods:  We measured survivin mRNA levels by real-time RT-PCR in specimens of oral mucosa (15 from normal mucosa, 17 from potentially malignant lesions, 17 from neoplasms). Scores were compared using Kruskal–Wallis test and post hoc according to Conover. Chi-squared test was used for dichotomous data.
Results:  The median relative levels of survivin mRNA resulted six for normal mucosa, eight for potentially malignant lesions, 13 for cancers: differences among these three groups were statistically significant, as between cancer and potentially malignant lesions. Expression in normal mucosa and potentially lesions group showed no significant difference. Low, but not marginal expression of survivin in normal mucosa is a new finding, and it could be explained with the higher sensibility of our methods.
Conclusions:  Survivin expression in oral potentially malignant lesions might indicate a progressive deregulation of expression paralleling oncogenesis, particularly during the first stages of process, suggesting a putative predictive role for survivin.     

Stromal myofibroblasts in oral leukoplakia and oral squamous cell carcinoma

Objectives: Oral leukoplakia (OL) is the main potentially malignant disorder and oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral mucosa. Stromal myofibroblasts play an important role in tumor invasion and metastasis, due to its ability to modify the extracellular matrix. This study aimed to evaluate the presence of stromal myofibroblasts in OL and OSCC. Differences in the presence of myofibroblasts among OL with distinct grades of epithelial dysplasia as well as between histologically high- and low-invasive OSCC were also assessed. Study Design: A total of 30 OL and 41 OSCC from archival formalin-fixed, paraffin-embedded specimens were evaluated. 10 samples of normal oral mucosa were used as a control. Myofibroblasts were identified by immunohistochemical detection of alpha smooth muscle actin and its presence was classified as negative, scanty or abundant. Differences in the presence of myofibroblasts among OL with distinct grades of epithelial dysplasia as well as between high- and low-invasive OSCC were analyzed using the Mann-Whitney test. Results: Myofibroblasts were not detected in normal oral mucosa and OL, whatever its histological grade. In OSCC, the presence of stromal myofibroblasts was classified as negative in 11 (26.8%), scanty in 15 (36.6%), and abundant in 15 samples (36.6%). The presence of stromal myofibroblasts was statistically higher in high-invasive OSCC than in low-invasive OSCC (p<0.05). Conclusions: Stromal myofibroblasts were not detected in OL, indicating that these cells are not important during oral carcinogenesis. Nevertheless, stromal myofibroblasts were heterogeneously detected in OSCC and its presence was higher in tumors with a more diffuse histological pattern of invasion. These findings suggest that myofibroblasts are associated with the creation of a permissive environment for tumor invasion in OSCC. Key words:Leukoplakia, oral squamous cell carcinoma, myofibroblast.     

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.     

Stromal myofibroblasts in oral leukoplakia and oral squamous cell carcinoma

Objectives: Oral leukoplakia (OL) is the main potentially malignant disorder and oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral mucosa. Stromal myofibroblasts play an important role in tumor invasion and metastasis, due to its ability to modify the extracellular matrix. This study aimed to evaluate the presence of stromal myofibroblasts in OL and OSCC. Differences in the presence of myofibroblasts among OL with distinct grades of epithelial dysplasia as well as between histologically high- and low-invasive OSCC were also assessed. Study Design: A total of 30 OL and 41 OSCC from archival formalin-fixed, paraffin-embedded specimens were evaluated. 10 samples of normal oral mucosa were used as a control. Myofibroblasts were identified by immunohistochemical detection of alpha smooth muscle actin and its presence was classified as negative, scanty or abundant. Differences in the presence of myofibroblasts among OL with distinct grades of epithelial dysplasia as well as between high- and low-invasive OSCC were analyzed using the Mann-Whitney test. Results: Myofibroblasts were not detected in normal oral mucosa and OL, whatever its histological grade. In OSCC, the presence of stromal myofibroblasts was classified as negative in 11 (26.8%), scanty in 15 (36.6%), and abundant in 15 samples (36.6%). The presence of stromal myofibroblasts was statistically higher in high-invasive OSCC than in low-invasive OSCC (p<0.05). Conclusions: Stromal myofibroblasts were not detected in OL, indicating that these cells are not important during oral carcinogenesis. Nevertheless, stromal myofibroblasts were heterogeneously detected in OSCC and its presence was higher in tumors with a more diffuse histological pattern of invasion. These findings suggest that myofibroblasts are associated with the creation of a permissive environment for tumor invasion in OSCC.     

Human papillomavirus as a risk factor in oral carcinogenesis: a study using in situ hybridization with signal amplification

Introduction:  It is still controversial whether human papillomavirus (HPV) can be considered a risk factor in oral carcinogenesis. The aim of this study was to detect HPV DNA in 50 cases diagnosed as oral leukoplakias, with different degrees of epithelial dysplasia, and as oral squamous cell carcinomas, using in situ hybridization with signal amplification (CSA-ISH).
Methods:  HPV DNA was assessed in paraffin sections using CSA-ISH with a wide-spectrum biotinylated DNA probe. In HPV-positive cases, genotyping with specific probes to HPV types 6/11, 16/18 and 31/33 was performed.
Results:  The overall prevalence of HPV infection was 24%, markedly higher than that found in the control group. Results showed a discrete proportional relationship in the indices found in leukoplakia with no dysplasia, leukoplakia with dysplasia, and squamous cell carcinoma, but this was not statistically significant. When separating the group of leukoplakia by degrees of dysplasia, this relation of proportion was not observed. In genotyping, HPV types 16/18 were the most prevalent, and types 6/11 were only found in groups of mild or no dysplasia.
Conclusion:  The results suggest that HPV is not likely to play a role in the progression of malignant transformation in oral lesions. Nevertheless, the increased prevalence of HPV infection compared to normal oral mucosa and the fact that high-risk HPV types were the most frequently identified do not allow the exclusion of HPV as a risk factor in oral carcinogenesis.     

High frequency of hypermethylation of p14, p15 and p16 in oral pre-cancerous lesions associated with betel-quid chewing in Sri Lanka

Background:  Oral squamous cell carcinoma and the most common oral pre-malignancies appear to be related to the habit of betel-quid chewing in Sri Lanka. Although hypermethylation of the tumour suppressor genes in oral cancer have been well documented, little information has been available concerning hypermethylation in oral pre-cancerous lesions. In the present study, we investigated the hypermethylation of p14, p15 and p16 in pre-cancerous lesions including epithelial dysplasia and submucous fibrosis.
Methods:  All samples were obtained from patients with a betel-quid chewing habit in Sri Lanka. Sixty-four patients were clinically diagnosed with leukoplakia, and histopathologically diagnosed with mild or severe dysplasia. Ten patients were diagnosed with submucous fibrosis without epithelial dysplasia. CpG island hypermethylation was assessed by a methylation-specific PCR method. Immunohistochemical staining was performed using anti-p53 antibodies.
Results:  A high frequency of hypermethylation of p14, p15 and p16 was detected in the pre-cancerous lesions, although no hypermethylation was found in normal epithelium. The frequency of hypermethylation was higher than that of positive staining for p53 mutation except in the case of p16 in mild dysplasia. No significant correlation was observed between p53-positive reactions and hypermethylation in any lesions. The hypermethylation was highly detectable even in p53-negative lesions, suggesting that hypermethylation of p14, p15 and p16 occur regardless of whether the lesions have p53 mutations or not.
Conclusions:  The present study indicates that hypermethylation may be involved in the pathogenesis of oral pre-cancerous lesions associated with betel-quid chewing in Sri Lanka.     

口腔黏膜癌变过程中Bmi-1及P16蛋白的表达及意义

目的:了解Bmi-1及P16蛋白在口腔黏膜癌变过程中的表达情况,探讨Bmi-1-P16通路在口腔鳞癌发生发展中的作用及意义。方法::正常口腔黏膜10例、上皮异常增生31例、口腔鳞癌61例的石蜡包埋组织,采用免疫组化SP法检测Bmi-1及P16表达情况,分析二者的相关性及其临床病理学意义。结果:Bmi-1在正常口腔黏膜、上皮异常增生及OSCC组织中的阳性率分别为0%、29%(9/31)和62.3%(38/61);P16在正常、上皮异常增生及OSCC组中的阳性率分别为100%(10/10)、77.4%(24/31)和47.5%(29/61)。OSCC中Bmi-1阳性率在P16阴性组高于P16阳性组,差异有统计学意义(P<0.05),Spearman相关分析显示两者间具负相关关系(r=-0.414,P<0.05)。Bmi-1阳性表达及Bmi-1高表达且P16失表达与OSCC临床分期及淋巴结转移密切相关(P<0.05)。结论:Bmi-1过表达是口腔黏膜癌变过程中的早期事件,口腔鳞癌中Bmi-1过表达可能与P16失表达有关并与临床分期及淋巴结转移密切相关,有可能作为临床评估口腔鳞癌浸润、转移和预后的参考指标之一。     

Gene expression analysis by oligonucleotide microarray in oral leukoplakia

Background:  Oral leukoplakias (LP) are the most frequent types of oral pre-cancerous lesions, but there is no accurate assessment of this malignant transformation or even genetic diagnosis of the oral epithelial dysplasia. We need to identify the new genetic diagnosis system of the epithelial dysplasia.
Methods:  Oligonucleotide microarray was used to analyze expression patterns of 29 952 genes in 10 LP patients. We compared the different gene expressions between mild dysplasia cases and severe dysplasia cases.
Results:  Ninety-six genes expressed differentially were selected as candidates for up-regulated in severe dysplasia. Subsequently, we further selected 16 genes with highest differentially expression. By hierarchical clustering analysis, the 10 cases were divided mild dysplasia from severe dysplasia.
Conclusions:  The 16 genes are suggested as biomarker gene sets of efficacy and quickly recognized in the development of oral epithelial dysplasia.