Endoscopic advances in the management of gastric cancer and premalignant gastric conditions

Gastric cancer is the fifth most common cancer and in 2018,it was the third most common cause of cancer-related deaths worldwide.Endoscopic advances continue to be made for the diagnosis and management of both early gastric cancer and premalignant gastric conditions.In this review,we discuss the epidemiology and risk factors of gastric cancer and emphasize the differences in early vs latestage gastric cancer outcomes.We then discuss endoscopic advances in the diagnosis of early gastric cancer and premalignant gastric lesions.This includes the implementation of different imaging modalities such as narrow-band imaging,chromoendoscopy,confocal laser endomicroscopy,and other experimental techniques.We also discuss the use of endoscopic ultrasound in the diagnosis and staging of early gastric cancer.We then discuss the endoscopic advances made in the treatment of these conditions,including endoscopic mucosal resection,endoscopic submucosal dissection,and hybrid techniques such as laparoscopic endoscopic cooperative surgery.Finally,we comment on the current suggested recommendations for surveillance of both gastric cancer and its premalignant conditions.

血清外泌体hsa_circ_0008035在胃癌前病变和早期胃癌中的临床意义

目的 探讨血清外泌体hsa_circ_0008035在早期胃癌(GC)及癌前病变中的临床意义。方法 2012年1月~2017年12月于我院就诊的GC病人90例(GC组)、癌前病变病人外周血样本89例(Pre组),同期纳入45例健康志愿者外周血样本作为对照(NC组),实时荧光定量聚合酶链式反应(qRT-PCR)检测血清外泌体hsa_circ_0008035水平。绘制受试者工作特征(ROC)曲线评估血清外泌体hsa_circ_0008035的诊断价值。通过内镜检查随访Pre组病人疾病进展情况。基于circBase和RegRNA 2.0靶点预测软件获得hsa_circ_0008035潜在的microRNA(miRNA)靶点。结果 与NC组比较,GC组和Pre组病人血清外泌体hsa_circ_0008035表达水平显著上调,其中GC组升高最为明显(P<0.05)。与传统肿瘤标志物检测比较,外泌体hsa_circ_0008035诊断GC及Pre的曲线下面积(AUC)、敏感性、准确性均显著提高,假阴性率和假阳性率显著降低(P<0.05)。在区分早期GC和Pre病人时的AUC为0.681,灵敏度和特异度为66.35%和83.31%。Pre组病人中位随访5.3年,21例病人发生疾病进展,这部分病人诊断为疾病进展时血清外泌体hsa_circ_0008035表达水平较基线值显著上调(P<0.001),基线时血清外泌体hsa_circ_0008035表达水平也较未发生疾病进展的病人普遍上调(P=0.005)。对于GC组病人,中晚期GC(TNM分期Ⅲ~Ⅳ期)病人血清外泌体hsa_circ_0008035表达水平高于早期GC病人,差异有统计学意义(P<0.05)。hsa_circ_0008035靶通路预测结果显示,hsa_circ_0008035含有hsa-miR-599、hsa-miR-17-3p、hsa-miR-1256和hsa-miR-375种子序列及相关的常见下游靶点。结论 血清外泌体hsa_circ_0008035表达在早期GC及癌前病变病人中普遍上调,对早期GC、胃癌前病变的诊断和疾病进展的评估均有一定的临床意义。

P^（53） PROTEIN OVEREXPRESSION IN PREMALIGNANT AND MALIGNANT LESIONS OF ORAL MUCOSA：IMMUNOHISTOCHEMICAL OBSERVATION

Ｐ^（５３） ＰＲＯＴＥＩＮ ＯＶＥＲＥＸＰＲＥＳＳＩＯＮ ＩＮ ＰＲＥＭＡＬＩＧＮＡＮＴ ＡＮＤ ＭＡＬＩＧＮＡＮＴ ＬＥＳＩＯＮＳ ＯＦ ＯＲＡＬ ＭＵＣＯＳＡ：ＩＭＭＵＮＯＨＩＳＴＯＣＨＥＭＩＣＡＬ ＯＢＳＥＲＶＡＴＩＯＮＰ^（５３）ＰＲＯＴＥＩ...

Helicobacter pylori and cytokine gene variants as predictors of premalignant gastric lesions

Gastric cancer remains the third leading cause of mortality from cancer worldwide and carries a poor prognosis,due largely to late diagnosis.The importance of the interaction between Helicobacter pylori(H.pylori)infection,the main risk factor,and host-related genetic factors has been studied intensively in recent years.The genetic predisposition for non-hereditary gastric cancer is difficult to assess,as neither the real prevalence of premalignant gastric lesions in various populations nor the environmental risk factors for cancer progression are clearly defined.For non-cardiac intestinal-type cancer,identifying the factors that modulate the progression from inflammation toward cancer is crucial in order to develop preventive strategies.The role of cytokines and their gene variants has been questioned in regard to non-self-limiting H.pylori gastritis and its evolution to gastric atrophy and intestinal metaplasia;the literature now includes various and non-conclusive results on this topic.The influence of the majority of cytokine single nucleotide polymorphisms has been investigated for gastric cancer but not for preneoplastic gastric lesions.Among the investigated gene variants onlyIL10T-819C,IL-8-251,IL-18RAP917997,IL-22 rs1179251,IL1-B-511,IL1-B-3954,IL4R-398 and IL1RN were identified as predictors for premalignant gastric lesions risk.One of the most important limiting factors is the inhomogeneity of the studies(e.g.,the lack of data on concomitant H.pylori infection,methods used to assess preneoplastic lesions,and source population).Testing the modifying effect of H.pylori infection upon the relationship between cytokine gene variants and premalignant gastric lesions,or even testing the interaction between H.pylori and cytokine gene variants in multivariable models adjusted for potential covariates,could increase generalizability of results.

Role of the Chinese Herbal Medicine Xianhuayin on the Reversal of Premalignant Mucosal Lesions in the Golden Hamster Buccal Pouch

Aim To investigate the role of the Chinese herbal medicine Xianhuayin on the reversal of 7,12-dimethylbenz[a]anthracene （DMBA）-induced premalignant mucosal lesions in the oral buccal pouch of golden hamsters. Methodology The animals were randomly divided into a non-diseased control group （n=5） and an experimental group including 50 animals in which the buccal mucosa had been painted with DMBA （0.5% in acetone） to generate an oral mucosa premalignant lesion. Animals in the experi- mental group were further divided into Xianhuayin-treated group （n=30）, untreated prem＇alignant lesion group （n=10） and normal saline （NS）-treated group （n=10）. The cheek （buccal） pouch mucosa of the golden hamsters in each group was observed with light and electron microscopy eight weeks after intragastric administration with NS or Xianhuayin. Results In the non-diseased control group, the buccal mucosa was keratinized and stratified squamous epithelium under a light microscope. In the untreated premalignant lesion group, variable degrees of epithelial dysplasia was observed. The irregular epithelial mucosa gradually became distinct in the Xianhuayin-treated group. Scanning electronic microscopic （SEM） analysis showed that surface of the cells exhibited honeycomb structures in the hamster of untreated- group. The cells were morphologically irregular, overlapped and loosened in the untreated premalignant lesion group. Most of the cell surface exhibited honeycomb structure in the Xianhuayin-treated group. Transmission electronic micro- scopic （TEM） analysis showed that buccal mucosal epithelial cells were morphologically regular in the non-diseased control group. Desmosomes and tonofibrils were reduced and the nucleus was morphologically irregular in the untreated premalignant lesion group. In the Xianhuayin-treated group, the widening intercellular gap was gradually reduced, desmosomes and the cells becoming morphologically regular. No significant difference was observed between the hamsters in NS-treated group and those in the untreated premalignant lesion group. Significant therapeutic efficacy was observed in the group receiving Xianhuayin. Conclusion Xianhuayin is effective in the reversal of DMBA-induced premalignant lesions in the buccal pouch of golden hamsters.

Effects of folic acid on epithelial apoptosis and expression of Bcl-2 and p53 in premalignant gastric lesions

AIM: To evaluate the effects of folic acid on epithelial apoptosis and expression of Bcl-2 and p53 in the tissues of premalignant gastric lesions.METHODS: Thirty-eight patients, with premalignant gastric lesions including 18 colonic-type intestinal metaplasia(IM)and 20 mild or moderate dysplasia, were randomly divided into a treatment group (n = 19) receiving folic acid 10 mg thrice daily and a control group (n = 19) receiving sucralfate 1 000 mg thrice daily for 3 mo. All patients undervvent endoscopies and four biopsies were taken prior to treatment and repeated after concluding therapy.Folate concentrations in gastric mucosa were measured with chemiluminescent enzyme immunoassay. Epithelial apoptosis and the expression of Bcl-2 and p53 protein in gastric mucosa were detected with flow cytometric assay.RESULTS: The mean of folate concentration in gastric mucosa was 9.03±3.37 μg/g wet wt in the folic acid treatment group, which was significantly higher than 6.83±3.02 μg/g wet wt in the control group. Both the epithelial apoptosis rate and the tumor suppressor p53expression in gastric mucosa significantly increased after folic acid treatment. In contrast, the expression of Bcl-2oncogene protein decreased after folic acid therapy.CONCLUSION: These data indicate that folic acid may play an important role in the chemoprevention of gastric carcinogenesis by enhancing gastric epithelial apoptosis in the patients with premalignant lesions.

Endoscopic submucosal dissection for premalignant lesions and noninvasive early gastrointestinal cancers

AIM: To investigate the indication, feasibility, safety, and clinical utility of endoscopic submucosal dissection (ESD) in the management of various gastrointestinal pathologies. METHODS: The medical records of 60 consecutive patients (34 female, 26 male) who underwent ESD at the gastroenterology department of Kocaeli University from 2006-2010 were examined. Patients selected for ESDhad premalignant lesions or non-invasive early cancers of the gastrointestinal tract and had endoscopic and histological diagnoses. Early cancers were considered to be confined to the submucosa, with no lymph node involvement by means of computed tomography and endosonography. RESULTS: Sixty ESD procedures were performed. The indications were epithelial lesions (n = 39) (33/39 adenoma with high grade dysplasia, 6/39 adenoma with low grade dysplasia), neuroendocrine tumor (n = 7), cancer (n = 7) (5/7 early colorectal cancer, 2/7 early gastric cancer), granular cell tumor (n = 3), gastrointestinal stromal tumor (n = 2), and leiomyoma (n = 2). En bloc and piecemeal resection rates were 91.6% (55/60) and 8.3% (5/60), respectively. Complete and incomplete resection rates were 96.6% (58/60) and 3.3% (2/60), respectively. Complications were major bleeding [n = 3 (5%)] and perforations [n = 5 (8.3%)] (4 colon, 1 stomach). Two patients with colonic perforations and two patients with submucosal lymphatic and microvasculature invasion (1 gastric carcinoid tumor, 1 colonic adenocarcinoma) were referred to surgery. During a mean follow-up of 12 mo, 1 patient with adenoma with high grade dysplasia underwent a second ESD procedure to resect a local recurrence. CONCLUSION: ESD is a feasible and safe method for treatment of premalignant lesions and early malignant gastrointestinal epithelial and subepithelial lesions. Successful en bloc and complete resection of lesions yield high cure rates with low recurrence.

EXPRESSION OF p16,CYCLIN D1 AND RB PROTEIN IN GASTRIC CARCINOMA AND PREMALIGNANT LESIONS

Objective: To investigate the expression of p16, cyclin D1 and Rb protein in gastric carcinoma and premalignant lesions including dysplastic gastric mucosa and intestinal metaplasia gastric mucosa. Methods: Using SP immunohistochemical methods, the expression of pl6, cyclin D1 and Rb proteins was detected in 10 specimens of normal gastric mucosa, 15 specimens of dysplastic gastric mucosa, 15 specimens of intestinal metaplasia gastric mucosa, 30 specimens of gastric carcinoma. The clinical characteristics of the 30 patients with gastric carcinoma were analysed to explore the relationship between the parameter detected and biological action of gastric cancer. Results: Expression of p16 protein was detected in 90% of normal gastric mucosa, 86.67% of dysplastic gastric mucosa, 86.67% of intestinal metaplasia gastric mucosa, 36.67% of gastric carcinoma. The positive rate of p16 protein expression in gastric carcinoma is significantly lower than that in normal gastric mucosa and gastric premalignant lesions mucosa (P<0.01). Expression of cyclin D1 protein was detected in 10% of normal gastric mucosa, 20% of dysplastic gastric mucosa, 20% of intestinal metaplasia gastric mucosa, 53.33% of gastric carcinoma. The positive rate of cyclin D1, protein expression in gastric carcinoma is significantly higher than that in normal gastric mucosa and gastric premalignant lesions mucosa (P<0.05). Expression of Rb protein was detected in 90% of normal gastric mucosa, 80% of dysplastic gastric mucosa, 80% of intestinal metaplasia gastric mucosa, 50% of gastric carcinoma. The positive rate of Rb protein expression in gastric carcinoma is significantly lower than that in normal gastric mucosa (P<0.05). The expression of p16, cyclin D1 gene were associated with the degree of differentiation of gastric carcinoma, lymphnodes metastasis and distant metastasis. Conclusion: p16, Cyclin D1 and Rb gene play important role in gastric carcinoma genesis. The expression of p16, cyclin D1 and Rb gene have some value to the diagnosis at earlier stage of gastric cancer. Detection of expression of p16, cyclin D1 gene would be helpful to judge the prognosis of gastric cancer.

Determination of telomerase activity and its clinical significance in gastric cancer and premalignant lesions

In order to explore the role of telomerase activity (TA) in the development and progression of gastric cancer (GC) and if TA can be used as an indicator for the early diagnosis of GC, TA in 176 specimens of gastric mucosa of 57 cases of chronic atrophic gastritis (CAG), 18 intestinal metaplasia (IM), 8 dysplasia (Dys), 65 GC obtained through operation or endoscopy was determined with PCR-based TRAP assay. Meanwhile, operative specimens of GC were analyzed with serial dilution. It was found that TA was detected in 24. 6% of CGA, 38. 9% of IM, 37.5% of Dys and 92.3% of GC, but not detected in 28 cases of normal tissues. TA detection was not related to patients’ sex, tumor location, size, depth of invasion, differentiation, lymph node metastasis and clinicalstage. Telomerase activity in premalignant lesions indicates that it plays a crucial role in the development and progression of GC. Thus the determination of telomerase activity is helpful to predict the progress of premalignant changes and to diagnose early GC.

Effect of Impaired Lung Function on the Development and Progression of Endobronchial Premalignant Lesions

Background: Chronic obstructive pulmonary disease (COPD) and presence of endobronchial premalignant lesions (EPL) are individual risk factors for lung cancer (LC). However, effect of impaired lung function (ILF) on the natural history of EPL has not been explored. Patients and Methods: This study included 217 high-risk participants from a hospital-based LC surveillance cohort who underwent pulmonary function testing followed by bronchoscopy with endobronchial biopsies. Baseline histopathology diagnoses included 91 cases (41.9%) with squamous metaplasia (SM), 25 (11.5%) with squamous dysplasia (SD), 1 (0.5%) with in-situ carcinoma and 5 (2.3%) with invasive LC. Follow-up biopsies were obtained for 69 patients, and 16 (23.2%) patients demonstrated progression to a higher grade lesion. Regression models were used to evaluate the relationship between ILF and EPL. All the models were adjusted for age, gender and tobacco smoking. Results: Patients with FEV1% of <50% had 4.5 times greater risk of being diagnosed with an EPL [95% confidence interval: 1.93-10.80] and 8-fold greater risk of SD, compared to patients with FEV1% ≥80. COPD was associated with 2.7 and 4.8 times greater risk of SM and SD, respectively. The mean time to progression to a higher-grade lesion was shorter in COPD patients compared to patients without COPD (27 versus 50 months, p = 0.02). Conclusion: Our results indicate that ILF may be a predictor of prevalence and progression of EPLs among patients at high risk of LC. Therefore, spirometry can be a complementary pre-screening tool for identifying patients with EPL who need more intense LC surveillance.

Actinic Cheilitis: Clinical Characteristics Observed in 75 Patients and a Summary of the Literature of This Often Neglected Premalignant Disorder

Actinic cheilitis can progress to squamous cell carcinoma in 20% of cases. The purpose of this study was to identify the clinical characteristics of 75 patients with actinic cheilitis and to summarise the current literature concerning actinic cheilitis. A total of 75 patients were evaluated over a 3-year period. The medical history, physical examination results and images were collected from each patient. Demographic data were collected and analysed. To review the literature, the relevant data were collected from scientific journals in the last 30 years. The mean age of the patients was 56 years old;42 patients (56%) were female, and 66 patients (88%) were white. Nineteen (25.3%) patients reported at least one symptom, including pain, burning and itching. Sixty-five (86.7%) patients presented actinic cheilitis only in the lower lip. All of the patients reported sun exposure, and 44 (58.6%) patients were exposed for more than 10 years. The main clinical aspects investigated and analysed included dryness (100%), flaking (72%) and white lesions (57.3%). Lip assessment is extremely important in medical and dental care. From the 15 lesions assessed in the presence of actinic cheilitis, the most common clinical characteristics observed were dryness, flaking and white lesions. It is imperative to know the clinical aspects that may be encountered in actinic cheilitis in order to achieve early diagnosis, thus avoiding lip squamous cell carcinoma transformation.

Significance of β-tubulin Expression in Breast Premalignant Lesions and Carcinomas

OBJECTIVE To explore the expression of β-tubulin in premalignant lesions and carcinomas of the breast,and to observe the relationship of its expression with breast cancer pathological features. METHODS The expression of β-tubulin was detected immunohistochemically in 50 specimens of premalignant lesions of the breast(ADH and Peri-PM with ADH),50 specimens of breast in situ ductal carcinomas(DCIS),and 50 specimens of invasive ductal carcinomas(IDC).Thirty specimens of normal breast tissues served as a control group. RESULTS Immunohistochemical analysis showed that:the differences among the 4 groups(normal breast tissues,breast premalignant lesions,DCIS and IDC,P<0.05)were significant, and there were also statistically significant differences between any 2 groups(P<0.05)except for the β-tubulin positive expression comparing DCIS versus IDC(P>0.05).In addition,β-tubulin was expressed at a higher level in Peri-PM with ADH compared to ADH(P<0.05).Following the degree of breast epithelial hyperplasia involved,and its development into carcinoma,the β-tubulin positive expression displayed an elevating tendency. We also found a significant positive relationship of β-tubulin expression with lymph node metastasis(P<0.05),but no significant correlation with histological grading and nuclear grade. CONCLUSION Centrosome defects may be an early event in the development of breast cancer and they can also promote tumor progression.Studies of aberrations of centrosomal proteins provide a new way to explore the mechanism of breast tumorigenesis.

人类口腔粘膜癌前损害发生发展过程中CDNK2基因作用的研究：Ⅰ.

新近发现，ＣＤＫＮ_２基因是第一个直接参与细胞周期调控的抑癌基因，但ＣＤＫＮ_２基因及其产物Ｐ１６蛋白在口腔粘膜癌前损害发生、发展过程中的作用及变化尚未见公开报导。本研究采用ＬＳＡＢ免疫组织化学染色技术研究发现：上皮单纯增生、上皮异常增生及无转移浸润性鳞状细胞癌中均有Ｐ１６蛋白表达，其阳性反应既可见于胞核，也可见于胞浆；随着细胞恶性程度的增高其阳性反应强度及阳性细胞数量呈递增趋势，且阳性反应的异质性明显增加。至转移性浸润性鳞状细胞癌阶段，Ｐ１６蛋白的阳性反应强度稍弱于前几个阶段的结果；转移浸润癌的原发灶及其转移淋巴结中的肿瘤上皮Ｐ１６蛋白的阳性反应都仅限于胞浆。

应用荧光差异显示法对胃癌及癌前病变相关基因的研究

背景与目的:一般认为胃癌是由癌前病变(慢性萎缩性胃炎、肠化生和不典型增生)逐步发展形成的。mRNA差异显示法是筛选肿瘤发生、发展中差异表达基因的有用方法。在胃癌、癌前病变中寻找差异表达的基因将有助于确定胃癌发生前的胃粘膜组织的分子变化。方法:应用荧光mRNA差异显示技术分析胃癌(2例)、癌前病变(2例)和正常胃粘膜(2例)组织,鉴别并分离差异表达的基因片段,进行PCR再扩增。将扩增cDNA片段克隆后进行测序,测序结果提交GenBank,经BLAST软件检索以进行同源性分析。RT-PCR检测血影蛋白基因在胃癌(7例)、癌前病变(7例)和正常胃粘膜(7例)的表达。结果:发现4个差异表达的cDNA片段,其中3个cDNA片段在胃癌中高表达,1个cDNA片段在正常组织和癌前病变组织中高表达。1个在胃癌组织中高表达的cDNA片段与血影蛋白基因(SPTAN1)同源,RT-PCR检测也发现血影蛋白基因在胃癌组织中高表达。另外3个与GenBank中已知的基因序列同源,但其功能目前尚不清楚。结论:所发现的4个差异表达的基因有3个在胃癌组织中高表达,其中SPTAN1基因在胃癌组织的表达比正常胃粘膜及胃异型增生组织表达明显高。

绞股蓝对金地鼠颊囊癌前病变细胞动力学影响的研究

对癌前病变的研究是攻克癌症的重要领域之一。为了研究口腔粘膜癌前病变致癌过程的发生机制，探寻有效的防癌阻癌药物，本实验采用Salley法诱导金地鼠颊囊上皮癌变，以中草药绞股蓝（GP）行阻断试验，并以光镜结合增殖细胞核抗原（PCNA）和溴脱氧尿嘧啶（BrdU）等免疫组化方法，动态观察GP的疗效，结果发现该药能推迟白斑的出现时间和降低出现率，并能明显降低致癌率。用药组的PCNA和BrdU阳性细胞标识率明显低于模型组，且始终处于较低水平，证实了GP的防癌效果和对细胞异常增殖的抑制作用。

放大色素内镜在胃黏膜癌前病变诊断中的价值

目的:探讨放大色素内镜在胃黏膜癌前病变诊断中的应用价值.方法:应用电子放大内镜,结合美蓝染色,对180例患者的胃黏膜糜烂灶进行细微结构形态学观察,将胃黏膜小凹的形态分为:A型(圆点状)、B型(短小棒状)、C型(稀疏而粗大的线状)、D型(斑块状)、E型(绒毛状)和F型(小凹结构模糊不清、消失或伴异常增生毛细血管)6型,并与观察部位活检所得的病理组织学改变进行比较分析.结果:A,B型胃小凹主要见于正常胃黏膜,而C,D,E和F型分别见于活动性、萎缩性炎症和肠上皮化生及轻、重度异型增生的胃黏膜.E型黏膜约81.8%(99/121)为肠上皮化生.F型黏膜常提示病灶已出现不同程度的异型增生86.3%(69/80),F型黏膜伴异常增生毛细血管,89.9%出现异型增生.结论:放大色素内镜能准确识别胃小凹的形态,尤其是准确识别E和F型,有助于对肠上皮化生及异型增生等胃黏膜癌前病变的镜下诊断.

血清胸苷激酶1在26055例健康体检人群肿瘤风险筛查中的应用

目的:探讨血清胸苷激酶1(serum thymidine kinase 1,STK1)在健康体检肿瘤风险筛查中的应用价值。方法:采用点印迹免疫增强发光法,检测长沙地区8家健康体检机构26 055例健康体检人群血清胸苷激酶1水平。结果:该体检人群中STK1阳性率(STK1>2 pmol/L)为2.61%;STK1升高组中60.35%的研究对象检出癌前病变和/或与肿瘤发生相关的病理改变;中度/重度增生性疾病(乳腺小叶增生、前列腺增生)者STK1升高比例明显增加。结论:在健康体检肿瘤风险筛查中,血清胸苷激酶1是早期发现肿瘤生长的预警信号。

金地鼠颊囊癌前病变模型的细胞动力学变化特征

对金地鼠颊囊癌前病变模型的研究，在防治口腔上皮癌肿上具有重要意义。本实验采用增殖细胞核抗原（PCNA）和澳脱氧尿吨院（BrdV）等免疫组化方法，结合光镜和电镜，对DMBA诱导的金地鼠颊囊癌前病变模型的细胞动力学变化进行观察，发现该模型的癌前病变发展过程中存在S期细胞增多和DNA合成活跃的特征，从而揭示了模型的细胞动力学改变基础。

p53、PCNA在口腔粘膜癌前病变中的表达及其临床意义

目的观察ｐ５３和ＰＣＮＡ在口腔粘膜癌前病变中的表达特征，进一步探讨其临床意义。方法对５０例临床疑为癌前病变的患者行局部组织活检、光镜检查，作出病理诊断；同时采用免疫组织化学方法进行ｐ５３和ＰＣＮＡ的标记，并将两者结果做比较。结果在癌前病变中，随着上皮细胞的异常增生从基底层向角化层发展，ｐ５３和ＰＣＮＡ阳性表达细胞也随着同步发展。病变伴不同程度异常增生的各病例阳性表达程度之间有显著差异（Ｐ＜０．０１）。结论ｐ５３和ＰＣＮＡ在口腔粘膜癌前病变中的表达呈同步性。且与病变细胞的异常增生程度呈正相关；ｐ５３在癌前病变中的阳性表达可能是其发生癌变的早发事件；癌变的发生可在上皮异常增生的较早期。故ｐ５３和ＰＣＮＡ的检测有利于临床上早期发现有异常增生倾向的病变。

PCNA、p53在口腔粘膜癌前病变及鳞癌中表达的免疫组化研究

应用免疫组化方法对39例口腔粘膜癌前病变和癌中的增殖细胞核抗原（PCNA）、突变型P53的表达进行检测。结果表明：从LP、LK到ISC，其PCNA和P53的阳性表达均呈递增趋势。提示PCNA、P53表达程度与细胞增殖程度和分化程度关系密切。