HPV与Survivin在口腔上皮组织中致癌作用研究

目的:研究口腔鳞癌(OSCC)及口腔黏膜白斑(OLK)组织中HPV感染与Survivin的表达,探讨上皮组织肿瘤的形成机制。方法:应用原位杂交法和免疫组化染色法分别检测30例OSCC组织,20例OLK组织及20例正常口腔黏膜组织中HPV及Survivin的表达情况。结果:Survivin在OSCC中的表达高于OLK中的表达,具有统计学意义。HPV阴性的OSCC中Survivin的表达明显高于HPV阳性OSCC组织;HPV阳性的OLK中survivin的表达明显高于HPV阴性的OLK组织。结论:Survivin可能通过抑制细胞凋亡调节HPV对口腔上皮的致癌作用,HPV感染对Survivin的表达水平存在调节作用。     

大鼠舌癌变过程中生存素、Bcl-2和p53蛋白的表达

目的 探讨生存素(survivin)蛋白在大鼠舌癌变过程中的表达及其与Bcl-2、p53蛋白表达的相关性.方法 0.002%4-硝基喹啉-1-氧化物(4一nitro-quinoline 1-oxide,4NQO)饮水喂养SD大鼠9～36周建立大鼠舌癌变模型,用免疫组化二步法检测60例大鼠舌癌变过程中生存素、Bcl-2及p53蛋白的表达.结果 36例止常组织中生存素蛋白表达仅1例,而11例异常增生组织中其表达为6例,11例口腔癌组织中其表达为10例.生存素蛋白在正常舌黏膜、异常增生黏膜及舌癌中的阳性表达差异有统计学意义(P<0.001),异常增生及口腔癌组织中生存素蛋白表达显著高于正常黏膜中的表达(P<0.01).在17例生存素蛋白表达阳性的大鼠舌组织中,Bcl-2蛋白阳性表达12例,p53蛋白阳性表达8例;生存素蛋白表达与Bcl-2、053蛋白表达呈正相关(P<0.01).结论 生存素蛋白的表达增高和口腔鳞状上皮的异常增生、癌变有关,提示生存素可能参与了口腔癌的发生、发展;生存素、Bcl-2及p53蛋白的表达可能在口腔癌的发生、发展中起协调作用.     

Survivin蛋白在人成釉细胞瘤中的表达及意义

目的:探讨survivin在成釉细胞瘤中的表达及意义。方法:采用免疫组织化学S-P法检测70例成釉细胞瘤(ameloblastoma, AB)、 15例恶性AB、30例正常口腔黏膜中survivin的表达。采用SPLUS13.0软件包对数据进行统计学分析。结果:AB、恶性AB中survivin明显表达,恶性AB中阳性表达率最高,为100%,其次为AB(82.9%);正常口腔黏膜轻微表达,其阳性率为30%,各组间差异显著(P<0.05)。结论:AB中survivin高表达,且明显高于正常口腔黏膜。Survivin可能参与AB的发生与发展,AB的侵袭性增加和恶变与survivin的高表达相关。     

端粒酶蛋白催化亚基(hTRT)mRNA在口腔鳞癌形成过程中的表达

目的:观察端粒酶催化蛋白基因hTRT在口腔粘膜恶性转化不同阶段中的表达,探讨其与口腔粘膜细胞恶性程度的关系。方法:用原位杂交技术检测82例标本,其中正常口腔粘膜7例、上皮单纯性增生7例、上皮异常增生30例、原位癌8例、口腔粘膜鳞癌30例。结果:正常口腔粘膜、上皮单纯性增生组织中hTRT的mRNA表达较弱,阳性信号仅局限于上皮基底层及副基底层间,阳性率21.4%(3/14);上皮异常增生中hTRTmRNA阳性表达见于多层上皮细胞,并随细胞异形性增高而表达增强,阳性率46.7%(14/30);口腔粘膜鳞癌组织中hTRT的mRNA有较强阳性表达,阳性率81.6%(31/38)。结论:端粒酶hTRT基因的表达与口腔粘膜细胞的恶性程度密切相关,端粒酶的重新激活在口腔鳞癌的形成过程中起了关键性作用     

Increased survivin expression in high-grade oral squamous cell carcinoma: a study in Indian tobacco chewers

BACKGROUND: Oral cancer is one of the five leading sites of cancer in the Indian population. In the present study we analyzed the expression of apoptosis regulating genes, viz. survivin, Bcl-2, Bax and p53 in precancerous and cancerous lesions of the buccal mucosa of Indian tobacco chewers. METHOD: Paraffin-embedded tissue samples from 38 patients with primary oral squamous cell carcinoma (OSCC) and 17 patients with leukoplakia were used. The expression of survivin, Bcl-2, Bax, and p53 was evaluated using immunohistochemical staining method. RESULTS: Thirty-six percent OSCC were found to be positive for nuclear p53 staining while none of the precancerous lesions showed p53 positivity. Survivin, Bcl-2 and Bax expression was found to increase with increased grade of malignancy. Increase in survivin expression was statistically most significant (P < 0.001). CONCLUSION: Increased expression of anti-apoptotic survivin in high-grade tumors suggests that survivin is likely to contribute significantly to apoptosis resistance in response to therapy.     

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.     

survivin在口腔鳞状细胞癌中的表达及其与 bcl-2,P53,bax表达之间的关系

目的初步探讨口腔鳞状细胞癌中凋亡抑制蛋白survivin的表达和临床意义,以及survivin的表达与bcl-2,P53,bax表达之间的关系。方法采用免疫组化二步法,DAB染色。27例口腔鳞癌和1例乳腺癌阳性对照病例手术前均未进行放疗、化疗或生物治疗。结果27例口腔鳞癌组织中survivin阳性表达率为88.89%(24/27),11例正常组织中survivin没有表达。在口腔鳞癌不同的临床病理分级survivin的表达有差异(P<0.05),其表达随着临床病理分级的增加而增加。Survivin在有淋巴结转移者阳性表达率(100%)高于无淋巴结转移者(82.35%),但统计学比较无差异(P>0.05)。口腔鳞癌中survivin的表达在不同的年龄组和性别间无差异(P>0.05),而在不同部位的鳞癌中表达有差异(P<0.05)。口腔鳞癌中survivin的表达和bcl-2,突变型P53的表达成正相关,(P<0.05),而与bax的表达成负相关,(P<0.05)。结论①Survivin可作为口腔鳞癌诊断的一项重要指标;②Survivin可作为口腔鳞癌基因治疗和免疫治疗的靶分子;③在口腔鳞癌基因治疗方面可以考虑协同抑制突变型P53和bcl-2的表达,或者提高bax的表达来提高疗效。     

端粒酶hTR基因在口腔癌前病变及鳞癌中的表达

目的探讨端粒酶ｈＴＲ基因在口腔癌前病变及鳞癌中的表达。方法用原位杂交技术检测８２例标本,其中正常口腔粘膜７例,上皮单纯性增生７例,上皮异常增生３０例,原位癌、鳞癌３８例。结果正常口腔粘膜及上皮单纯性增生组织中ｈＴＲ表达较弱,阳性细胞主要位于基底层,检出率２８．５６％（４／１４）。癌前病变中随着异常增生程度的增加,ｈＴＲ表达逐渐增强,阳性细胞逐步由基底层向棘层波及,检出率６０％（１８／３０）。原位癌及鳞癌均有较强的ｈＴＲ表达,检出率为８１．５８％（３１／３８）。结论端粒酶的激活可能出现在口腔癌前病变的晚期阶段,在口腔鳞癌的形成过程中起了关键性作用。     

Survivin在口腔鳞癌组织中的表达及其与COX-2相关性研究

目的:探讨凋亡抑制基因Survivin在口腔鳞癌组织中的表达及其与COX-2表达的相关性。方法:运用S-P免疫组化技术,检测Survivin和COX-2蛋白在50例口腔鳞癌组织、10例正常口腔黏膜组织中的阳性率。结果:Survivin蛋白在10例正常口腔黏膜组织中呈阴性,而在50例口腔鳞癌组织中有42例阳性,占84%,差异有极显著性差异(P<0.01),COX-2蛋白在口腔鳞癌组织中的阳性率为86%(43/50)。Survivin蛋白阳性率与年龄和性别不相关,而与COX-2蛋白阳性呈正相关(P<0.05)。Survivin蛋白在低分化癌组织中的表达比在高分化癌中高,但在统计学上无明显差异性。结论:肿瘤组织中Survivin蛋白的高阳性表达对口腔鳞癌的发生发展起重要作用;COX-2蛋白在口腔鳞癌组织中也有高阳性表达,并与Survivin有相关性。两者可能存在共同的激活机制,从而抑制口腔鳞癌细胞的凋亡。     

口腔鳞状细胞癌发生发展过程中P21wafl表达的研究

目的 :了解P21wafl表达与口腔鳞状细胞癌发生发展的关系。方法 :利用免疫组化技术 ,进行石蜡切片回顾性研究。结果 :P21wafl蛋白在口腔上皮单纯增生的表达率为75% (12/16) ,显著高于口腔不典型增生 (26.09% ,6/23) (p<0.05)和鳞状细胞癌(28.26%,13/46) (p<0.05) ;P21wafl阳性标本的阳性细胞计数与组织恶性程度成正相关。结论 :P21wafl表达的下调是口腔鳞癌发生发展过程中较早期事件 ,P21wafl表达率结合P21wafl阳性细胞计数在口腔粘膜癌前病变监视方面是一项有用的指标。     

多肿瘤抑制基因1在口腔黏膜癌前病变和鳞癌中的变异

目的　检测多肿瘤抑制基因 1(multipletumorsuppressor 1,MTS1)基因在口腔黏膜癌前病变和鳞癌中的表达和变异 (纯合性缺失和突变 )情况 ,以期发现MTS1在口腔黏膜恶变发生发展中的作用。方法　采用免疫组化SP法检测MTS1的表达情况 ;同时采用PCR、SSCP技术检测相同标本中MTS1基因exon1和exon2的纯合性缺失和突变情况。结果　口腔癌前病变中MTS1基因全部表达 ,无基因缺失和突变。鳞癌中MTS1的表达阳性率 6 0 % ;有 10例发生exon1和 (或 )exon2的纯合性缺失 ,4例基因突变 ,总变异率为 31.1% (14 / 4 5 ) ;伴有局部淋巴结转移的鳞癌的基因变异率为5 7.1% ,不伴有淋巴结转移的为 8.3% ,两者间差异有显著性 (P <0 .0 5 )。结论　MTS1基因在口腔癌前病变中无改变 ,不能作为检测口腔癌前病变的生物学指标 ;MTS1基因改变在口腔鳞癌的发生、发展中起一定作用     

新疆部分维族、汉族口腔黏膜癌前病变及口腔鳞状细胞癌P16蛋白表达的研究

目的 探讨新疆维吾尔族、汉族口腔黏膜癌前病变及口腔鳞状上皮细胞癌的发生与发展过程中P16蛋白表达的意义。方法 采用免疫组化LSAB法对40例口腔扁平苔藓（维吾尔族20例，汉族20例），43例口腔白斑（维吾尔族23例，汉族20例）和60例口腔鳞状上皮细胞癌（维吾尔族24例，汉族41例）分别进行检测。结果口腔鳞状上皮细胞癌组织中P16蛋白阳性率为32．3％，明显低于口腔白斑（55．8％）和口腔扁平苔藓（72．5％），P＜0．005，维族与汉族之间的的差异均无统计学意义（P＞0．05）。结论 P16蛋白表达缺失在口腔鳞状上皮细胞癌的发生与发展过程中起重要作用；据本研究资料，尚不能认为P16蛋白的表达在维族与汉族之间的差异有显著性。     

MAGE-A antigens in lesions of the oral mucosa

Oral squamous cell carcinoma develops continuously out of predamaged oral mucosa. For the physician and pathologist, difficulties arise in distinguishing precancerous from cancerous lesions. MAGE-A antigens are tumor antigens that are found solely in malignant transformed cells. These antigens might be useful in distinguishing precancerous from cancerous lesions. The aim of this study was to verify this assumption by comparing MAGE-A expression in benign, precancerous, and cancerous lesions of the oral mucosa. Retrospectively, biopsies of different oral lesions were randomly selected. The lesions that were included are 64 benign oral lesions (25 traumatic lesions (oral ulcers), 13 dental follicles, and 26 epulis), 26 oral lichen planus, 123 epithelial precursor lesions (32 epithelial hyperplasia found in leukoplakias, 24 epithelial dysplasia found in leukoplakias, 26 erythroplasia with oral epithelial dysplasia, and 41 carcinomas in situ in erythroleukoplakias). The lesions were immunohistochemically stained with the poly-MAGE-A antibody 57B, and the results were compared. Biopsies of oral lichen planus, oral ulcers, dental follicles, epulis, and leukoplakia without dysplasia showed no positive staining for MAGE-A antigens. Leukoplakia with dysplasia, dysplasia, and carcinomata in situ displayed positive staining in 33%, 65%, and 56% of the cases, respectively. MAGE-A antigens were not detectable via immunohistochemistry in benign lesions of the oral mucosa. The staining rate of dysplastic precancerous lesions or malignant lesions ranged from 33% to 65%. The MAGE-A antigens might facilitate better differentiation between precancerous and cancerous lesions of the oral mucosa.     

口腔鳞癌中碱性成纤维细胞生长因子和凋亡抑制因子Survivin的关系

目的：检测口腔鳞癌组织中碱性成纤维细胞生长因子(basic fibroblast growth factor，bFGF)和Survivin的表达，探讨二者在口腔鳞癌中的关系和临床意义。方法：收集口腔鳞癌标本42例(其中有淋巴结转移者14例)和10例正常口腔粘膜组织，用免疫组织化学染色法检测bFGF和Survivin的表达情况。结果：口腔鳞癌中bFGF表达阳性率为69．05％(29／42)，Survivin的表达阳性率为80．95％(34／42)。二者共同表达率为61．90％(26／42)，其表达阳性程度呈显著正相关。结论：bFGF和Survivin在口腔鳞癌的发展中可能起协同作用。     

P53蛋白在口腔鳞状细胞癌发生过程中的表达及意义

本研究采用微波处理暴露抗原,通过免疫组化ＬＳＡＢ方法对ＮＯＭ６例,ＯＰＬ２８例,ＯＳＣＣ３４例中Ｐ５３蛋白表达进行观察,其ＮＯＭ无表达;在ＯＰＬ中的表达率为８２％随着上皮异常增生的程度加重,表达率呈上升趋热（Ｐ〈０．０５）;而在ＯＳＣＣ中表达率为６５％,随着肿瘤的分极增加,表达率呈下降趋势（Ｐ〈０．０５）。结果表明,Ｐ５３蛋白在ＯＰＬ和ＯＳＣＣ中呈异常表达,并与ＯＰＬ程度和ＯＳＣＣ分级有关,Ｐ５３     

Evaluation of survivin as a prognostic marker in oral squamous cell carcinoma

J Oral Pathol Med (2010) 39 : 368–375 Background: Poor prognosis of oral squamous cell carcinoma (OSCC) is partly attributed to the lack of significant tumor marker for accurate staging and prognostication. We have evaluated survivin, which is a member of the inhibitor of apoptosis family as a cancer marker associated with proliferation, angiogenesis, oral carcinogenesis, and OSCC patient survival, as we reported a prognostic significance of survivin expression in lymph node previously. Methods: To evaluate survivin expression in six OSCC cell lines, Western blotting was performed. Hamster oral carcinogenesis model was used to observe changes of survivin expression in oral carcinogenesis. Finally, we assessed the diagnostic and prognostic significance of survivin in a series of 38 primary OSCC through immunohistochemistry (CD31, PCNA) and Kaplan–Meier’s test. Results: Survivin expression was detected in all OSCC cell lines at a varying level but not observed in normal gingival keratinocyte cells. In hamster model, survivin expression was observed from 8 weeks through 16 weeks and the intensity of expression became strong until 16 weeks. Clinicopathological analysis revealed a significant correlation between survivin expression and lymph node metastasis (P = 0.006) and proliferation (P < 0.001). However, there was no significant relationship with differentiation, micro vessel density, and cancer stage based on TNM. Survivin overexpression had a significant negative effect on survival of patients. Conclusions: These results demonstrate the significant relationship between survivin expression and oral carcinogenesis and aggressiveness of OSCC including survival rate of patient. Survivin therefore may be used as a significant cancer marker to gain prognostic information of OSCC.     

环氧酶-2在人舌鳞癌及癌前病变组织中的表达

目的　探讨环氧酶 2 (COX 2 )在口腔癌前病变和舌癌组织中的表达及其意义。方法　采用免疫组化法(IHC)检测 6 0例人舌鳞状细胞癌和 2 0例癌前病变石蜡标本的COX 2表达。结果　COX 2在正常舌粘膜上皮组织中仅有 1例 (1/ 10 )弱表达 ,在舌粘膜上皮异常增生及舌癌组织中的阳性率分别为 6 5 0 %、78 3% ,舌癌组织中的表达强度明显高于舌粘膜上皮异常增生组织 (P =0 0 2 17)。结论　COX 2在舌癌及其癌前病变中有不同程度的高表达 ,可以作为化学预防和治疗的靶点     

Management of oral carcinoma: benefits of early precancerous intervention

Management of oral precancerous lesions remains polarised between interventional surgery and conservative treatment. We have previously shown the efficacy of carbon dioxide laser excision for both diagnosis and treatment of oral precancerous lesions. The aim of this study was to review the clinicopathological details of a group of patients in whom pre-existing but occult invasive carcinoma was diagnosed histopathologically in specimens excised by laser. We retrospectively reviewed 169 patients who attended the Maxillofacial Dysplasia Clinic at Newcastle General Hospital with single, new oral premalignant lesions over a 5-year period (2004-2008). They were all treated by laser excision of lesions that were confirmed to be dysplastic from examination of preoperative incisional biopsy specimens. There was a significant correlation between the results of diagnostic incisional, and laser excision, biopsy specimens (p < 0.01), but 15 patients had signs of occult invasive carcinoma in the excision specimens (9%). In all cases the carcinomas were completely excised by the laser. Carbon dioxide laser excision is not only an effective treatment of precancerous lesions, but also facilitates early diagnosis and management of oral carcinoma at a stage when it is otherwise clinically undetectable.