口腔鳞状细胞癌患者血清TSGF、SCC-Ag、CEA的表达及其临床意义

目的　探讨联合检测血清中恶性肿瘤特异性生长因子(TSGF) 、鳞状细胞癌抗原(SCC-Ag)及癌胚抗原（CEA）在口腔鳞状细胞癌诊断中的价值。方法　采集58例口腔鳞状细胞癌患者、36例口腔良性肿瘤患者及30例健康人血液,分别检测血清中TSGF、SCC-Ag和CEA含量。结果　口腔鳞状细胞癌组TSGF、SCC-Ag、CEA含量明显高于口腔良性肿瘤组和健康组(P< 0.05)。口腔鳞状细胞癌组TSGF、SCC-Ag、CEA阳性率分别为74.14%、55.17%、24.14%,联合检测阳性率为86.21%。结论　血清TSGF、SCC-Ag、CEA分别检测对口腔鳞状细胞癌的诊断有一定意义,联合检测提高口腔鳞状细胞癌的诊断率。     

存活蛋白在口腔鳞状细胞癌中的表达及意义

目的 探讨存活蛋白(survivin)与口腔鳞状细胞癌发生和预后的相关性.方法 收集口腔鳞状细胞癌21例(试验组)及良性肿物10例(对照组)的口腔脱落细胞、唾液、血清及组织,应用酶联免疫吸附测定和实时定量聚合酶链式反应技术检测标本中存活蛋白及mRNA表达.结果 试验组脱落细胞的存活蛋白表达质量浓度[(43.93±33.30) ng/L]显著高于对照组[(8.49±3.73)ng/L] (P＜0.01);口腔脱落细胞存活蛋白表达浓度随淋巴结转移而升高(P＜0.05);口腔鳞状细胞癌组织存活蛋白mRNA的表达通过相对定量倍数关系比较,为正常组织的3.3倍,差异有统计学意义(P＜0.01).结论 存活蛋白在口腔癌的发生过程中起重要作用,口腔脱落细胞的存活蛋白检测可早期诊断口腔鳞状细胞癌并判断预后.     

TRAIL在口腔鳞状细胞癌和白斑中的表达及意义

目的：研究肿瘤坏死因子相关凋亡诱导配体（TNF-related apoptosis inducing ligand,TRAIL）在口腔鳞状细胞癌（OSCC）组织及白斑中的表达及意义。方法：采用免疫组化Maxvision两步法检测54例口腔鳞状细胞癌、30例口腔黏膜白斑、22例正常口腔黏膜组织中TRAIL的表达水平。结果：TRAIL在口腔鳞状细胞癌组织和黏膜白斑中的表达水平均低于其在正常口腔黏膜中的表达水平（P〈0.05）,分别为33.3%、56.7%、86.4%,其在癌组织与白斑中表达水平的差异无统计学意义。TRAIL在高分化癌组织中的表达水平高于中低分化组（P〈0.05）。TRAIL在不同临床分期组间及淋巴结转移与非转移组间表达水平的差异无统计学意义。结论：TRAIL表达的抑制可能与口腔鳞状细胞癌及口腔黏膜白斑的发生有关,并且TRAIL可能参与了初始阶段的正常黏膜向癌组织的转化。TRAIL在口腔鳞状细胞癌中的表达水平与癌组织的分化程度相关。     

p16和p53蛋白在口腔白斑和鳞状细胞癌中表达的比较研究

目的比较p16和p53在口腔白斑和口腔鳞状细胞癌中异常表达的情况。方法对17例健康者的口腔粘膜、60例白斑患者和40例口腔鳞状细胞癌患者的病损组织进行了p16和p53蛋白的免疫组化染色。结果正常口腔粘膜、白斑单纯增生、白斑异常增生和口腔鳞状细胞癌的p16阳性率分别为100％、90％、60％和35％，p53蛋白的阳性率分别为12％、27％、50％和73％，p16阳性率和细胞染色强度指数（stainning intensity index，SII）分别与口腔粘膜组织恶性度的增高显著负相关；p53阳性率和S11分别与口腔粘膜组织恶性度的增高显著正相关。p16和p53在不同组织中的阳性率显著负相关；p16和p53在白斑异常增生的协同失活率达23％，在口腔鳞状细胞癌中达到42．5％。p16阳性率、p16SII、p53SII及两种基因均异常的比率在口腔鳞状细胞癌无淋巴结转移和口腔鳞状细胞癌有淋巴结转移患者之间均有显著差异。结论p16可作为早期监视口腔白斑恶变、监测口腔鳞状细胞癌发展进程和判断口腔鳞状细胞癌预后的分子生物学指标。p16和p53失活在白斑癌变和口腔鳞状细胞癌的发展过程中可能有叠加效应。     

口腔鳞状细胞癌中p27与Skp2蛋白表达及其意义的初步观察

目的:探讨p27与Skp2蛋白在口腔鳞状细胞癌组织中的表达及其与口腔鳞状细胞癌临床病理之间的相互关系。方法:免疫组化SP法检测p27、Skp2蛋白在69例口腔鳞状细胞癌和12例正常口腔黏膜组织中的表达情况,并分析其与患者的年龄、性别、肿瘤的部位、临床分期、病理分级、颈淋巴结转移之间的相关性。结果:口腔鳞状细胞癌中p27蛋白的阳性率63.73%明显低于正常黏膜组织92.72%(P<0.05),Skp2蛋白在口腔鳞状细胞癌中的阳性率19.02%明显高于正常黏膜组织4.24%(P<0.05)。p27蛋白阳性表达率与肿瘤的临床分期、病理分级、颈淋巴结转移呈负相关(P<0.05),Skp2蛋白阳性表达率则与以上临床病理特征呈正相关(P<0.05);二者的阳性表达率与口腔鳞状细胞癌患者的年龄、性别、肿瘤部位无关(P>0.05)。p27蛋白在口腔鳞状细胞癌中的表达与Skp2蛋白呈负相关(P<0.05)。结论:Skp2蛋白表达与靶蛋白细胞周期抑制因子p27降解相关,可能参与了口腔鳞状细胞癌的发生、发展。联合检测p27和Skp2蛋白表达有助于判断口腔鳞状细胞癌的恶性程度和预后。     

乳腺丝氨酸蛋白酶抑制剂在口腔鳞状细胞癌中的表达及意义

目的 探讨乳腺丝氨酸蛋白酶抑制剂(marray serine proteinase inhibitor,Maspin)在口腔鳞状细胞癌中的表达及其与临床病理特征之间的关系.方法 应用免疫组织化学方法 对口腔鳞状细胞癌45例的癌组织及其癌旁上皮组织标本行Maspin蛋白含量的半定量测定,与各临床病理指标采用SPSS 13.0统计学软件进行统计学分析.结果 Maspin蛋白在口腔鳞状细胞癌组织中的表达(弱阳性31%,强阳性31%)显著低于癌旁上皮组织(弱阳性13%,强阳性87%),P=0.001;口腔鳞状细胞癌组织中Maspin蛋白的表达与淋巴结转移(P=0.038)、术后转移(P=0.004)呈负相关,与总体生存状况呈正相关(P=0.014).结论 Maspin蛋白的检测对口腔鳞状细胞癌患者判断预后具有重要价值.     

乳腺丝氨酸蛋白酶抑制剂在口腔鳞状细胞癌亚细胞中的表达及意义

目的 检测乳腺丝氨酸蛋白酶抑制剂(mammary serine proteinase inhibitor,Maspin)在口腔鳞状细胞癌亚细胞中的表达,观察其与口腔鳞状细胞癌患者临床病理特征之间的关系,以期为临床提供参考.方法 应用免疫组织化学方法对45例口腔鳞状细胞癌的癌组织标本行Maspin蛋白含量的半定量测定,统计其亚细胞定位表达,并与各临床病理指标进行统计学分析.结果 Maspin蛋白在口腔鳞状细胞癌胞核中表达的强阳性率为24%(11/45),弱阳性率为11%(5/45),阴性率为64%(29/45),细胞核表达与肿瘤大小(P=0.019)、淋巴结转移(P=0.011)及术后转移(P=0.017)呈负相关,与患者术后的生存时间呈正相关(P=0.030);Maspin蛋白在口腔鳞状细胞癌胞质中表达的强阳性率为31%(14/45),弱阳性率为31%(14/45),阴性率为38%(17/45),细胞质表达与淋巴结转移(P=0.038)、术后转移(P=0.004)呈负相关,与患者术后的生存时间呈正相关(P=0.014).结论 Maspin蛋白在口腔鳞状细胞癌胞核或胞质中的表达对判断预后可能具有重要价值.     

COX-2及PINCH蛋白在口腔鳞状细胞癌中的表达及其相关性研究

目的研究COX-2及PINCH蛋白在口腔鳞状细胞癌中的表达情况,探讨二者在口腔鳞状细胞癌中表达的相关性。方法采用免疫组织化学ABC法,检测20例正常口腔粘膜和57例口腔鳞状细胞癌石蜡存档标本中COX-2及PINCH蛋白的表达情况。结果COX-2蛋白在正常口腔粘膜中少量表达,而在口腔鳞状细胞癌中的表达明显增加,二者比较有显著性差异;在口腔鳞状细胞癌中,淋巴结转移组阳性表达率为73%(19/26),淋巴结无转移组阳性表达率为29%(9/31),二者差异有显著性;COX-2蛋白的表达与患者性别、年龄、肿瘤大小、部位和分化程度无相关性;COX-2与PINCH有明显的相关性。结论COX-2蛋白在口腔鳞状细胞癌的发生、发展中可能起着重要作用,并与口腔鳞状细胞癌的淋巴结转移相关,其转移机制可能与通过PINCH蛋白促进淋巴管生成有关。     

口腔鳞状细胞癌组织乏氧状况的初步研究

目的 检测口腔鳞状细胞癌组织乏氧程度,探讨口腔鳞状细胞癌组织乏氧影响因素,认识和利用肿瘤乏氧区域的特性,为治疗提供依据.方法 经临床和病理证实的口腔鳞状细胞癌组织石蜡标本42例,建立口腔鳞状细胞癌动物移植瘤模型,采用单光子发射计算机断层成像(single photon emission computerized tomography,SPECT)乏氧显像技术检测癌组织的乏氧程度;采用免疫组织化学方法检测肿瘤乏氧标志物(hypoxia inducible factorla,HIF-1α)在口腔鳞状细胞癌组织中的分布,并分析与临床病理资料的相关性.结果 乏氧显像剂在动物模型鳞状细胞癌组织内高浓度聚集,与肿瘤体积呈线性相关,相关指数为0.926(P＜0.05),呈全层乏氧;口腔鳞状细胞癌组织中HIF-1α蛋白高表达,且在低分化、淋巴结转移及高临床分期组中的表达较高分化、无淋巴结转移及低临床分期组高(P＜0.05);正常口腔黏膜组织巾HIF-1α无表达.结论 口腔鳞状细胞癌组织乏氧区域分布广泛.HIF-1α在口腔鳞状细胞癌组织中高表达,可能在口腔鳞状细胞癌的发生和发展中起重要作用.     

P33ING1b在口腔鳞状细胞癌中的表达及其临床意义

目的:观察P33ING1b蛋白在口腔鳞状细胞癌中的表达情况,探讨其临床病理意义。方法:采用免疫组织化学ABC法,检测20例正常口腔黏膜和57例口腔鳞状细胞癌石蜡存档标本中P33ING1b的表达情况,并分析P33ING1b蛋白表达情况与患者临床病理特征的关系。结果:P33ING1b在大部分正常黏膜有表达,以细胞核为主,阳性表达率为90.00%,在口腔鳞状细胞癌中的表达以细胞核、细胞质共同着色为主,阳性表达率为24.56%,二者比较差异有显著性(P<0.05)。口腔鳞状细胞癌中淋巴结转移组阳性表达率为46.15%(12/26),淋巴结无转移组阳性表达率为6.45%(2/31),二者比较有显著性差异(P<0.05)。结论:P33ING1b蛋白在口腔鳞状细胞癌的发生发展中可能有重要的作用。其表达由细胞核转移到细胞质可能是主要机制;P33ING1b蛋白的表达与淋巴结转移有关,可以作为判断预后的一个潜在生物学标志。     

ALDH1在OLP和LK组织中的表达及其意义

目的：通过检测干细胞标记物ALDH1在口腔扁平苔藓（OLP）和白斑（LK）中的表达水平,评价其与癌变的关系。方法：采用免疫组织化学SP法检测ALDH1在10例正常口腔黏膜,30例OLP,60例LK,10例口腔鳞癌（OS－CC）中表达水平;再检测ALDH1在30例癌变与30例未癌变LK中的表达差异。结果：ALDH1在正常口腔黏膜中不表达,在OLP、LK和OSCC中的表达率分别为26．7％,63．3％和90．0％（P＜0．05）;ALDH1在未癌变和癌变LK中的表达率分别是43．3％和83．3％（P＜0．01）。结论：ALDH1与口腔黏膜恶性潜能程度相关,可能是预测癌变的分子标记物。     

AgNOR count as objective marker for dysplastic features in oral leukoplakia

BACKGROUND: Dysplasia is an important feature of leukoplakia. Because agreement among oral pathologists is poor regarding lesional diagnosis, silver stainable nucleolar organizer regions (AgNORs) as replicatory markers may have a place in objectively characterizing dysplasia in tissue specimens. METHODS: We studied 41 normal oral epithelia, 51 oral leukoplakia (26 dysplastic, 25 non-dysplastic), and 51 cases of squamous cell carcinoma specimens for their mean AgNOR counts. RESULTS: Mean AgNOR counts increased gradually from normal epithelium to non-dysplastic to dysplastic leukoplakia to squamous cell carcinoma. Using ROC analysis, we determined a mean AgNOR count cut-point (2.37) that can be used to distinguish between dysplastic and non-dysplastic leukoplakia. The test had a sensitivity of 75% and specificity of 83% with area under the curve being 88%. CONCLUSIONS: Mean AgNOR count could be a valuable criterion for defining objective parameters for diagnosis/determination of dysplasia distinguishing between dysplastic and non-dysplastic leukoplakia.     

Patients with oral cancer developing from pre‐existing oral leukoplakia: do they do better than those with de novo oral cancer?

Background:  It has been suggested that patients with squamous cell carcinomas derived from oral leukoplakia have a better prognosis than patients with carcinomas that are not associated with oral leukoplakia.
Aim:  To study the mortality rate of 19 patients with a squamous cell carcinoma derived from pre-existing oral leukoplakia.
Method:  The mortality rate of 19 patients with a proven oral squamous cell carcinoma derived from a pre-existing oral leukoplakia was compared with that of a similar size group of patients with oral carcinoma without a pre-existing oral leukoplakia, being matched for gender, age, smoking habits, use of alcohol, oral subsite and histopathologic grade. Treatment in all patients was primarily by surgical excision. The mortality rates up to 5 years have been computed according to the Kaplan–Meier method.
Result:  No significant difference of the mortality rates up to 5 years of follow-up was observed between the two groups of patients.
Conclusion:  Patients with oral cancer developing from pre-existing oral leukoplakia do not do better than those with de novo oral cancer.     

Relationship of oral leukoplakia and cancer by immunohistochemical expression of EGF-receptor

To examine the relationship between the oral leukoplakia and cancer, an immunohistochemical study of the EGF-receptor was performed by the avidin-biotin peroxidase-complex method and silver enhancement with anti-human EGF-receptor antibody (Bio-yeda). Totally 61 cases of leukoplakias without relation to cancer, 20 cases of leukoplakias with relation to cancer and 31 cases of squamous cell carcinomas were examined. Seventy percent of leukoplakias and 55% of cancer cases were positive for the EGF-receptor. The proportion of the EGF-receptor-positive cells in the leukoplakia cases was slightly decreased in proportion to the degree of the epithelial dysplasia. The proportion of the EGF-receptor-positive cells in the poorly differentiated type cancer cases (3%) was fewer than that in the differentiated type cancer cases (31%). In the leukoplakia related to cancer, the leukoplakia and cancer of the same patient did not always show the same pattern of EGF-receptor.     

Fine needle aspiration cytology as a diagnostic test for oral squamous cell carcinoma

OBJECTIVE: The purpose of this study was to determine the possibility of using fine needle aspiration cytology (FNAC) as a primary diagnostic test in oral leukoplakia and squamous cell carcinoma.
MATERIALS AND METHODS: The sample consisted of 1 1 cases of oral leukoplakia and 60 cases of oral squamous cell carcinoma. FNAC and biopsy was done on all cases. A cytological and histopathological correlation was undertaken to determine the proportion of cancers that can be accurately diagnosed by FNAC and its ability to identify differentiation gradings of squamous cell carcinomas. A blind examination was undertaken.
RESULTS: In oral leukoplakias equal rates of true positive and false negative results were obtained. The overall positive correlation accounted for 33.33% with 33.33% inadequate FNACs. In oral squamous cell carcinomas 92.85% of true positive and 7.14% of false negative results were obtained. The differentiation gradings correlated in only 41.07%. The overall positive correlation was 86.66% with 6.66% inadequate FNACs.
CONCLUSIONS: The present study indicates that FNAC can be used as a reliable diagnostic test for oral squamous cell carcinoma but its use in oral leukoplakia is of limited value.     

不同癌基因在口腔白斑和鳞癌中表达的研究

目的 研究正常口腔黏膜，口腔黏膜白斑及口腔鳞癌组织中不同癌基因的表达。方法 通过HE染色确定口腔黏膜组织类型，提取组织中RNA，采用RT－PCR的方法研究不同组织中c-myc、ras、cyclinD1及bcl-2基因的表达。结果 正常口腔黏膜中未见c-myc、ras、cyclinD1及bcl-2基因表达；轻、中、重度异常增生白斑和鳞癌组织中c-myc、ras、cyclinD1及bcl-2基因表达显著增加。结论 c-myc、ras、cyclinD1及bcl-2基因的表达增加与口腔黏膜白斑及鳞癌的发生相关。     

Salivary 8-hydroxy-2-deoxyguanosine,malondialdehyde, vitamin C,and vitamin E in oral pre-cancer and cancer: diagnostic value and free radical mechanism of action

Objectives

The objectives of this study are to analyze oxidative DNA and lipid damage using salivary 8-hydroxy-2-deoxyguanosine (8-OHdG), malondialdehyde (MDA), and vitamins C and E in oral lichen planus lesions, oral leukoplakia, oral submucous fibrosis, oral squamous cell carcinoma (SCC), and controls and to determine the value of salivary biomarkers in the diagnosis of oral pre-cancer and cancer patients.

Materials and methods

Unstimulated saliva was collected from a group of patients diagnosed with 40 oral squamous cell carcinoma (OSCC), 40 oral lichen planus lesions, 40 oral leukoplakia, 40 oral submucous fibrosis, and from a control group of healthy age- and gender-matched individuals. Salivary 8-OHdG, MDA, and vitamins C and E were measured.

Results

Squamous cell carcinoma and pre-cancer patients showed significantly higher levels of salivary 8-OHdG and MDA and lower levels of vitamins C and E when compared to levels in healthy normal subjects. The specificity and sensitivity of the combination of 8-OHdG, MDA, vitamin C, and vitamin E are high for the diagnosis of oral pre-cancer and SCC compared to an individual biomarker approach using either 8-OHdG, MDA, or vitamin C and vitamin E independently.

Conclusions

This study indicates the presence of oxidative DNA and lipid damage in pre-cancerous and SCC patients. It is postulated that the mechanism may have a significant link to carcinogenesis in oral cancer. Detection of salivary 8-OHdG, MDA, vitamin C, and vitamin E can act as suitable diagnostic biomarkers of oral pre-cancer and cancer.

Clinical relevance

Of clinical importance is that salivary 8-OHdG, MDA, vitamin C, and vitamin E could play a significant role in oral cancer and pre-cancer patients and could therefore be useful for diagnosis in patients with oral lichen planus lesions, oral leukoplakia, oral submucous fibrosis, and oral squamous cell carcinoma.

     

Bcl-2、MDM2和p21在口腔白斑和口腔鳞状细胞癌中的表达水平研究

目的：了解Bcl-2、MDM2、p21在人口腔正常黏膜、白斑、鳞状癌细胞中的表达情况.方法：采用免疫组化二步法检测15例人正常口腔黏膜、15例单纯增生性白斑、10例异常增生性白斑,25例口腔鳞癌中Bcl-2、MDM2和p21蛋白的表达情况.结果：Bcl-2、MDM2蛋白在异常增生性白斑和口腔鳞癌中的表达明显高于正常口腔黏膜上皮细胞;p21蛋白在异常增生性白斑和口腔鳞癌中的表达明显低于正常口腔黏膜上皮细胞.结论：Bcl-2、MDM2和p21三者与口腔黏膜癌变具有相关性.     

Mutated and wild-type p53 expression and HPV integration in proliferative verrucous leukoplakia and oral squamous cell carcinoma

The frequencies of overexpression and mutation in the p53 tumor suppressor gene were examined in proliferative verrucous leukoplakia and oral squamous cell carcinoma with immunohistochemistry and single-strand conformation polymorphism analysis of DNA fragments amplified by polymerase chain reaction. Ten samples each of normal oral mucosa, proliferative verrucous leukoplakia, and squamous cell carcinoma were immunostained with antibodies against p53 protein; 8 of 10 cases of proliferative verrucous leukoplakia cases and 7 of 10 cases of oral squamous cell carcinoma were positive for p53 protein. Minimal staining was observed in normal oral tissues. The quantified labeling indexes demonstrated a range that corresponded to lesion progression. Single-strand conformation polymorphism analysis revealed p53 gene mutations within exons 5 to 8 in 40% (4 of 10) of the squamous cell carcinoma samples. Two of the 4 mutated squamous cell carcinoma samples lacked p53 expression. No p53 mutations were detected in proliferative verrucous leukoplakia tissues. Human papillomavirus 16 was identified in 2 of 7 p53 positive oral squamous cell carcinoma samples. Human papillomavirus 16 and 18 were identified in two of eight p53 positive proliferative verrucous leukoplakia samples. One p53 negative squamous cell carcinoma sample was positive for human papillomavirus 16 and had a mutation in exon 6 of the p53 gene. Human papillomavirus infection along with p53 expression plays a yet to be defined role in the pathogenesis of a limited number of cases of proliferative verrucous leukoplakia and squamous cell carcinoma. p53 Immunohistochemistry, p53 gene mutations, and human papillomavirus infection prevalence do not provide a means to differentiate between leukoplakia and carcinoma and do not provide a predictive test for progression of leukoplakia to carcinoma.