Immunohistochemical study of oral keratoses including lichen planus

Biopsies of non-ulcerated oral mucosa from 13 patients with oral lichen planus and 12 patients with leukoplakia were immunohistochemically stained using monoclonal antibodies to pan T, pan B, T helper and T suppressor/cytotoxic cells and the stained lymphocytes enumerated using an image analyser. The results show the preponderance of T cells infiltrating both oral lichen planus and leukoplakia. The T helper: T suppressor/cytotoxic cell ratio was the same (1:2) for both oral lichen planus and leukoplakia. A similar proportion of T suppressor/cytotoxic cells was found infiltrating the epithelium. These data indicate that T cell subset analysis is of no value in distinguishing oral lichen planus from other oral keratoses.     

Longitudinal study of TP53 mutations in eight patients with potentially malignant oral mucosal disorders

Objectives:  In a previous cross-sectional study, the authors found a higher rate of TP53 mutation in oral lichen planus (OLP) than in hyperkeratosis. By analysing for TP53 mutations in serial samples from patients on long-term follow-up of their oral lesions, it was hoped to determine if these mutations were related to disease progression.
Methods:  Eight patients presenting with lesions diagnosed clinically as oral leukoplakia or lichen planus were followed from 2 to 12 years. Two to five samples of archival biopsy tissue were analysed from each patient by constant denaturant gradient gel electrophoresis for hotspots A, B, C, D and exon 6.
Results:  Four patients were diagnosed clinically as OLP: two of these were confirmed histopathologically, one was diagnosed as non-specific hyperkeratosis and one as cancer. Four patients had leukoplakia only, with a histopathological diagnosis of hyperkeratosis. Seven patients had TP53 mutations, three of them on repeated occasions. All five patients who developed squamous-cell carcinoma had mutations. Two of them had mutated pre-malignant lesions, and one of these previously had a non-mutated cancer. Three patients had two different primary cancers, only one of them mutated. One patient developed a mutated cancer 5 years after the last mutation-free biopsy. Of the cancer-free patients, a lesion regarded clinically as cancer-suspicious in one case was mutated, in another patient two OLP lesions were mutated, the third had five biopsies taken during 8 years, all non-mutated.
Conclusions:  TP53 mutations may occur early or late in the development of oral squamous-cell carcinoma.     

Sequential immunohistochemical p53 expression in biopsies of oral lichen planus undergoing malignant evolution

Transformation in squamous cell carcinoma (SCC) may occur in a small percentage of patients affected by oral lichen planus (OLP), but the pathogenesis remains to be elucidated. Overexpression of p53 protein was investigated immunohistochemically in 28 cases of OLP, followed up by sequential biopsies for up to 96 months. In 15 cases (Group 1), no dysplastic changes or neoplastic transformation occurred during the follow-up period; in 7 cases, OLP and SCC were synchronously observed (Group 2), whereas in another 6 cases (Group 3) SCC developed several months or years after diagnosis of OLP. The percentage of p53-positive epithelial cells at first diagnosis was significantly higher in the cases of Groups 2 and 3 than in those of Group 1. In contrast, evaluation of growth fraction by MIB-1 monoclonal antibody did not show any statistical differences among the three groups. Although no conclusions can be drawn about the molecular pathway leading to neoplastic transformation of OLP, or about the role of p53, the results indicate that immunohistochemical evaluation of p53 expression may be a practical tool to select cases of OLP with a high risk of neoplastic transformation.     

COX-2、VEGF在口腔扁平苔藓、口腔白斑及口腔鳞状细胞癌中的表达

目的研究环氧合酶(COX)-2、血管内皮生长因子(VEGF)在口腔扁平苔藓(OLP)、口腔白斑(OLK)及口腔鳞状细胞癌(OSCC)组织中的表达及分布,探讨其在OLP、OLK癌变机制中的作用。方法采用免疫组化法检测33例OLP患者(单纯扁平苔藓19例,伴异常增生14例)、35例OLK患者(单纯增生14例、伴异常增生21例)、31例OSCC患者及10例正常对照者口腔黏膜组织(NOM)中COX-2、VEGF的分布和表达。应用统计分析软件SPSS 13.0对结果进行统计分析。结果COX-2、VEGF在正常口腔黏膜组织无表达或低表达;在单纯扁平苔藓组均为26.32%过表达;在扁平苔藓异常增生组分别为71.43%、64.29%过表达;在白斑单纯增生组过表达情况均为21.42%;在白斑异常增生组分别为80.95%、71.43%过表达;在口腔鳞状细胞癌组分别为93.55%、90.32%过表达;COX-2、VEGF在扁平苔藓异常增生组的表达明显高于单纯扁平苔藓组(P<0.05),低于OSCC组(P<0.05),与白斑异常增生组无明显差异(P>0.05)。COX-2的表达与VEGF表达呈明显正相关(r=0.595,P<0.01)。结论COX-2、VEGF在NOM、OLP及OLK伴异常增生、OSCC的表达逐渐增高,表明COX-2及VEGF与OLP、OLK的异常增生及癌变有关。     

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.     

KLF-6在口腔扁平苔藓恶变中的表达研究

目的 探讨KLF 6在口腔扁平苔藓发病机制及癌变中的作用。方法 分别采用免疫组化和Western blot方法对10例正常口腔黏膜、30例扁平苔藓患者和22例口腔鳞癌患者的上皮组织中KLF 6蛋白进行t检测,比较其在三者之间的差异。SPSS 14.0对数据进行检验。结果 扁平苔藓患者组织中KLF 6蛋白的表达明显低于正常口腔黏膜,两组之间具有显著性差异;口腔鳞癌患者组织中KLF 6蛋白的表达明显低于扁平苔藓组织,两组之间具有显著性差异。结论 KLF 6的表达异常可能在口腔扁平苔藓的发生发展及癌变的过程中起作用。     

EP—CAM在OLP和OSCC组织中的表达及意义

目的：观察上皮细胞黏附分子（Ep—CAM）在口腔正常黏膜、扁平苔癣（OLP）和鳞癌（OSCC）组织中表达的变化,分析Ep—CAM在口腔黏膜疾病及其癌变发病机制中的作用。方法：采用免疫组织化学法检测10例正常口腔黏膜、30例OLP（15例非糜烂型、15例糜烂型）及20例OSCC组织中Ep—CAM的表达变化。结果：Ep—CAM在正常黏膜组织阴性表达,而在非糜烂型OLP、糜烂型OLP及OSCC组织中表达逐渐增强。结论：Ep—CAM在口腔黏膜癌变的发展过程中可能具有一定的指示意义。     

Occurrence of oral leukoplakia and lichen planus in diabetes mellitus

The occurrence of oral leukoplakia and lichen planus in 1600 patients with diabetes mellitus (815 type 1: insulin-dependent, 761 type 2: non-insulin-dependent)-under care at the International Medicine Department-was studied. Precancerous lesions and conditions were diagnosed and grouped according to internationally accepted criteria. The prevalence of oral leukoplakia in diabetic patients was 6.2%, as compared to 2.2% in the healthy controls, that of oral lichen was 1.0% in the test-, and 0.0% in the control group. Leukoplakia and lichen both showed the highest occurrence in the second year of established diabetes, and their prevalence was higher among insulin-treated diabetics. Smokers were more often affected, by both kind of lesions, oral lichen showed a more frequent association with candidiasis. The prevalence of oral leukoplakia and lichen in diabetes mellitus patients was higher, than average ratios in population samples from the same country.     

Oral lichen planus: a retrospective study of 690 British patients

OBJECTIVE: This is the largest UK patient group with oral lichen planus (OLP) to be studied in terms of the demographic and clinical characteristics. MATERIALS AND METHODS: Data were taken from the medical records of 690 consecutive patients referred to Oral Medicine subsequently found to have clinical, and usually histopathological confirmatory features of OLP. Over two-thirds (68.7%) of the patients were Caucasians. RESULTS: Eighty-two per cent of the patients had been referred to a specialist Oral Medicine service by general dental practitioners, 62% of the patients being referred as a consequence of oral mucosal and/or gingival pain. Reticular OLP was the most common intra-oral presentation, but 60% of such lesions were accompanied by other clinical types of OLP. 95% of lesions were bilateral. About 13% of patients reported symptoms or signs, or had a known history of lichen planus or possible lichen planus affecting non-oral epithelia. In only 13% of patients did all signs and symptoms of OLP resolve within 12-246 months (median 35 months). A malignant transformation rate of 1.9% was observed in the present group. CONCLUSIONS: Oral lichen planus in UK persons almost always gives rise to bilateral reticular OLP, rarely resolves spontaneously, and has a low rate of malignant transformation.     

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。     

EMT在口腔鳞癌和扁平苔藓病理机制中的作用

上皮-间充质转化（epithelial-mesenchymal transition,EMT）,是上皮细胞通过特定的程序转化为间质细胞的生物学过程,EMT在胚胎发育、创伤愈合、肿瘤的侵袭迁移等过程中起重要作用,EMT在恶性肿瘤的侵袭迁移病理过程中的分子机制成为研究热点。EMT的发生涉及多种机制,与低氧微环境、炎症因子、细胞外基质及microRNA等有关。文中综合目前研究进展,就EMT在口腔鳞癌和扁平苔藓侵袭转移中的作用及其分子机制作一综述。     

口腔扁平苔藓癌变潜能探讨——P53基因表达及形态计量学研究

目的从P53基因的表达及细胞形态计量变化,研究口腔扁平苔藓（OLP)癌变的潜能。方法采用免疫组化SABC法对28例OLP病损P53基因表达情况进行检测;用图像分析技术,对其中16例OLP的细胞形态学变化进行测量及分析,并分别与正常口腔粘膜、上皮异常增生性白斑、及鳞癌比较。结果P53蛋白在正常口腔粘膜中表达阴性,但可在OLP、白斑（LK）角朊细胞及鳞癌（SCC）癌细胞中表达,阳性细胞数比例由OLP、LK到SCC依次递增,差异有显著性（P＜0.05）。细胞形态定量结果显示OLP各项参数值介于正常与白斑和鳞癌之间,与鳞癌差异显著（P＜0.05）。结论OLP是一种界于正常及癌之间的良性病损,具有一定的恶变潜能,但恶变潜能可能低于白斑。     

口腔白斑和扁平苔藓中TSGF的检测

目的 探讨恶性肿瘤特异性生长因（TSGF）的检测对口腔白斑和扁平苔藓的临床意义。方法 对45例鳞癌，12例白斑和32例扁平苔藓患者，测定其血中TSGF的浓度。结果 鳞癌的阳性率为53．33％，白斑为33．33％，扁平苔藓为25．00％。白斑与鳞癌的阳性率无显著性差异（P＞0．05）。扁平苔鲜与鳞癌的阳性率有显著性的差异（P＜0．05）。结论 检测患者血清中TSGF可做为临床预测口腔黏膜病是否有癌变倾向的初步手段。     

Decreased expression of p63 in oral lichen planus and graft-vs.-host disease associated with oral inflammation

BACKGROUND: Oral lichen planus (OLP) and graft-vs.-host disease (GVHD) are conditions with increased risk of malignant transformation to squamous cell carcinoma of the head and neck (SCCHN). The p63 gene encodes six different proteins and is expressed at high levels in SCCHN. METHODS: Biopsies from patients diagnosed with OLP and GVHD were analysed for p63 protein expression using antibodies distinguishing between the major isoforms expressed in normal epithelia, in parallel with biopsies from normal buccal mucosa and SCCHN. RESULTS: In OLP and GVHD a decreased expression of all p63 isoforms was seen, while expression of p53 protein was upregulated, compared with normal mucosa. In SCCHN, p63 was abundantly expressed and some tumours showed strong p53 staining, suggestive of p53 mutation. CONCLUSIONS: Decreased p63 and increased p53 expression in OLP and GVHD indicates a coordinated action of these two related proteins to protect the oral mucosae from the damaging effects of underlying inflammation. In SCCHN disruption of the TP53 gene and overrepresentation of certain p63 isoforms has been seen, indicating that this could lead to neoplastic transformation.     

Oral lichen planus – a demographic study

Among 20,333 Swedish people aged 15 yr and above, oral lichen planus was found in 1.9%; 1.6% among men and 2.2% among women. The highest prevalences were found in the age groups 65-74 and 55-64 yr. Reticular lichen planus was the most common type, found in 77.3%. The most prevalent intraoral location of lichen planus was the buccal mucosa, which was affected in 92%. Lichen planus was less prevalent among smokers than among non-smokers, except for the plaque type, which showed no difference in this context.     

口腔扁平苔藓损害组织中树突状细胞亚群数量和比例

目的：研究口腔扁平苔藓（oral lichen planw,OLP）组织中树突状细胞（dendritic cell,DC）的亚群数量和比例,探索其在OLP疾病中的作用。方法：收集正常对照（HC组）,萎缩糜烂型OLP（E－OLP组）,斑纹型OLP（R－OLP组）的颊黏膜,通过流式细胞术染色和免疫组化染色,检测朗格汉斯细胞（CD1a＋CD11cint／lo CD207＋MHC II＋）、髓样DC （CD11c＋MHC II＋）、浆细胞样DC（CD11cint／lo CD123＋MHC II＋）和细胞毒性T细胞（CD3＋CD8＋）在组织中的浸润情况。结果：收集样本23例（HC组5例,E－OLP组7例,R－OLP组11例）,Bartlett检验各组数据方差不齐,采用Kruskal－Wallis非参数检验。朗格汉斯细胞的中位数比例分别为0．092％（HC）、0．564％（E－OLP）和0．541％（R－OLP）,3组间无统计学差异;髓样DC的中位数比例分别为0．311％（HC）、0．996％（E－OLP）和0．448％（R－OLP）,其中E－OLP组与HC组之间有统计学差异（P＜0．05）;浆细胞样DC的中位数比例分别为0．090％（HC）、3．490％（E－OLP）和2．010％（R－OLP）,2组OLP组与HC组之间均有统计学差异（P＜0．05）;CD8＋T细胞的中位数比例分别为0．126％（HC）、4．210％（E－OLP）和1．850％（R－OLP）,2组OLP组与HC组之间均有统计学差异（P＜0．05）。结论：DC在OLP中数量和比例增加,可能与疾病的自身免疫发病机制有关。     

口腔黏膜扁平苔藓患者口腔黏膜组织中cyclin D1,ki-67及凋亡的表达研究

目的　检测口腔黏膜扁平苔藓 (OLP)患者口腔黏膜上皮凋亡增殖状况及细胞周期调控蛋白表达水平的变化 ,探讨OLP发病机制。方法　采用甲基绿 -派诺宁法及免疫组化SABC法分别检测 30例OLP患者及 2 0例正常对照者口腔黏膜组织的凋亡情况及细胞周期蛋白 (cyclinD1)、增殖细胞核抗原 (ki 6 7)的表达并进行细胞计数及统计学分析。结果　OLP组与对照组凋亡、ki 6 7、cyclinD1表达阳性率差异有显著性 (P <0 .0 5 ) ;与凋亡呈正相关。结论　OLP病变中 ,部分细胞受损进入凋亡性细胞死亡 ,同时发生了细胞周期紊乱、细胞增殖