颅锁骨发育不全综合征患者下颌骨喙突异常2例

颅锁骨发育不全综合征(cleidocranial dysplasia, CCD)是一种罕见遗传病,临床表现常为颅骨、锁骨、牙齿发育不全,较少出现下颌骨喙突异常,本文报道2例CCD患者喙突伸长,且1例患者存在RUNX2基因突变(NM＿001024630:exon5:c.586＿587del AG),为新突变。     

家族性锁骨颅骨发育不全的基因突变检测

目的 研究家族性锁骨颅骨发育不全家系的Cbfal基因突变。方法 对临床收集到的一个牙列异常、锁骨颅骨发育不全家系行外周血基因组DNA的提取，利用聚合酶链式反应，DNA直接测序检测突变。结果在该家系中每例患者均存在Cbfal基因外显子3中的杂合性突变，即cDNA674位G〉A的单碱基突变，从而使255位的精氨酸替换为谷氨酰胺（Pa55Q），改变了runt结构域的氨基酸序列。结论Cbfal基因的突变是引起此家系锁骨颅骨发育不全的致病原因。突变检测的结果可用于该家系后代的产前诊断。这也是在中国人家族性锁骨颅骨发育不全患者中首次检测到的基因突变。     

颅骨锁骨发育不全综合征的特征分析

目的:分析来自不同家族的骨锁骨发育不全综合征的发病特点.方法:对颅骨锁骨发育不全综合征患者进行体检,建立病历,摄片,分析牙、颌面及影像特点.结果:患者表现不同程度的颅骨、牙齿、锁骨发育障碍.结论:分析颅骨锁骨发育不全综合征的临床及影像特点有助于临床诊断及制定治疗方案.     

颅骨锁骨发育不全患者RUNX2基因突变检测——附1例报告

目的：研究颅骨锁骨发育不全（CCD）患者的RUNX2基因突变。方法：对1例患者进行全身健康状况及口腔专科检查,明确诊断为颅骨锁骨发育不全。提取患者全血基因组DNA,PCR扩增RUNX2基因,BLAST同源序列分析,检测基因突变位点。体外分离培养患者来源的牙囊细胞及正常对照牙囊细胞,cDNA测序验证基因突变。结果：患者RUNX2基因第2外显子插入TG突变,牙囊细胞cDNA测序结果相同,该突变型为c．309_310insTG。结论：成功发现了RUNX2基因新致病突变,补充了国内外CCD致病基因的突变位点数据库。     

锁骨颅骨发育不全综合征(CCD)1例报告

目的：分析1例锁骨颅骨发育不全综合征的典型病例。为临床正确诊断该类遗传性疾病提供临床依据。方法：对1例锁骨颅骨发育不全综合征患进行临床检查、染色体检查、并对其家族成员进行家系调查。结果：临床确诊锁骨颅骨发育不全综合征，主要临床表现为异常发育的锁骨，囟门的闭合不全，多生牙，身材矮小等一系列骨骼的改变。家系调查被诉怀疑有相关病患发生，染色体检查未见异常。结论：锁骨颅骨发育不全综合征是一种由于常染色体变异所造成的骨骼发育异常。及时正确地诊断该疾病，对于病患的进一步的正畸及修复治疗非常重要。     

颅骨锁骨发育不全综合征：1例家系报告及文献复习

颅骨锁骨发育不全综合征是一种先天性全身骨骼发育不全性疾病,临床罕见,以锁骨发育不良、囟门闭合延迟、方颅、乳牙脱落延迟、恒牙迟萌或阻生、多生牙以及颌骨形态异常为主要临床特征。本文报告1例颅骨锁骨发育不全综合征家系,并结合相关文献,对该病的发病率、发病机制、临床表现、诊断及治疗进行讨论。     

锁骨颅骨发育不全综合征(CCD)1例

颅骨锁骨发育不全综合征(cleidocranial dysplasia,CCD),是一种先天性全身骨骼发育不全性疾病,常为遗传性疾病,其主要临床特征是全身多发性骨骼发育畸形及面、牙的发育异常[1].关于锁骨发育异常的报道最早可追溯到1765年,本文就近期就诊的1名CCD患者进行个例报道,为广西地区首次报道该类疾病.     

颅锁骨发育不全1例及基因突变分析

颅锁骨发育不全是一种罕见的常染色体显性遗传疾病,以骨骼及牙齿发育异常为特征。本文对1例颅锁骨发育不全病例进行报道,并经基因检测,证实了一个新的移码突变。     

颅骨锁骨发育不全1例

颅骨锁骨发育不全综合征(cleidocranial dysplasia,CCD),又名Marie and Sainton综合征,是一种罕见的先天性遗传性疾病,出生发病率为十万分之一[1],表现为骨骼系统的发育畸形.     

AgNOR cut-point to distinguish mild and moderate epithelial dysplasia

Background:  Distinguishing mild and moderate epithelial dysplasia is difficult and controversial. We demonstrated earlier that silver-stainable nucleolar organizer region (AgNOR) is a simple, inexpensive and quantifiable method which can standardize this distinction reliably.
Objective:  To establish a cut-point mean AgNOR count for epithelial dysplasia validated by bootstrapping.
Methods:  One hundred oral leukoplakia biopsies at Dr R. Ahmed Dental College, Kolkata, India, examined for epithelial dysplasia using standard method (gold standard) were assessed for their mean AgNOR counts. A cut-point was selected employing receiver operating characteristic (ROC) curve. This estimate was stabilized by 10 000 resamples (with replacement) using parametric and non-parametric bootstrap, a Monte Carlo statistical method, corrected for bias to estimate standard errors (SE) of cut-point.
Results:  Area under the curve (AUC) was 74%; non-parametric method suggested mean AgNOR cut-point = 2.42 AgNORs/nucleus; parametric method suggested cut-point = 2.57. The cut-point 95% confidence intervals (CIs) (bias corrected and accelerated) from parametric method (2.31; 2.66) was lower than non-parametric (2.43; 2.82).
Conclusion:  Applying a conservative paradigm, taking the lowest of all bootstrap 95% CIs, we suggest that mean AgNOR count of 2.3 be used as a cut-point for distinguishing between mild and moderate dysplasia. This strategy will provide an inexpensive, meaningful, definitive, reproducible and consistent diagnostic test for epithelial dysplasia.     

McCune-Albright综合征伴甲状腺功能亢进1例报告及文献复习

McCune-Albright综合征（MAS）是一种临床罕见的疾病,其典型三联征包括多骨性骨纤维异常增殖症、牛奶咖啡色斑及性早熟。本文报告1例伴有甲状腺功能亢进的McCune-Albright综合征患者,并通过相关文献复习,阐述MAS的病因、临床表现、诊断及治疗等。     

Assessment of c-Jun, c-Fos and cyclin D1 in premalignant and malignant oral lesions

Some oral cancers are known to develop from dysplastic oral epithelium. In the present study, the expression of c-Jun, c-Fos, and cyclin D1 proteins in oral epithelial lesions with different degrees of dysplasia, and in oral squamous cell carcinomas (OSCCs) was evaluated. Eighteen cases of mild dysplasia, 23 cases of moderate to severe dysplasia and 24 OSCCs were studied immunohistochemically. Additionally, 15 sections of oral mucosa without any evidence of dysplasia were included in the study. Results: c-Jun expression increased according to the degree of oral dysplasia, with the greatest expression found in OSCC. c-Fos expression was intense in normal mucosa, reduced in mild dysplasia and high in moderate to severe dysplasia and in OSCCs. Cyclin D1 was expressed in only a few cases of moderate to severe dysplasia and in most of the OSCCs. Statistical analysis showed a correlation between the three proteins and the degree of epithelial alteration. The present results indicate a possible role of c-Jun and c-Fos in malignant transformation of oral mucosa.     

hMLH1 immunoexpression is related to the degree of epithelial dysplasia in oral leukoplakia

J Oral Pathol Med (2011) 40 : 153–159 Background: hMLH1 is a protein of the mammalian mismatch repair system responsible for genomic stability during repeated duplication. Relation between its altered expression linked to microsatellite instability has also been observed in oral leukoplakias (OL) and squamous cell carcinomas pointing to a possible role of hMLH1 in oral carcinogenesis. To our knowledge, this is the first study evaluating the immunoexpression of hMLH1 in OLs regarding their different degrees of epithelial dysplasia. Methods: Sixty‐two specimens of OL were classified in four groups: 17 without dysplasia, 19 with mild dysplasia, 16 with moderate dysplasia, and 10 with severe dysplasia. Immunohistochemistry for hMLH1 was performed, and percentage of positive cells was assessed. In the statistical analysis, P values <0.005 were considered significant. Results: hMLH1 immunoexpression showed decreasing indexes from lesions with lower degrees of dysplasia to lesions with more severe dysplasia. Statistical difference was found mainly between suprabasal layers and total indexes. Conclusions: hMLH1 immunoexpression was inversely related to the OL degree of dysplasia. The total epithelial hMLH1 index seems to be of more clinical relevance than the evaluation stratified by layers. Our findings also suggest a role of such alterations in this pathway of DNA repair as an early event in oral carcinogenesis.     

Immunohistochemical study of syndecan-1 down-regulation and the expression of p53 protein or Ki-67 antigen in oral leukoplakia with or without epithelial dysplasia

BACKGROUND: Leukoplakia is an oral pre-cancerous lesion that sometimes develops into squamous cell carcinoma. Therefore, leukoplakia with epithelial dysplasia is useful for studying carcinogenesis at the cellular level. The purpose of this study was to evaluate a potential association between the loss of syndecan-1 expression and the expression of p53 protein and Ki-67 antigen, and to identify reliable markers for predicting malignant changes in oral leukoplakia with epithelial dysplasia. METHODS: Changes in the expression of syndecan-1, p53, and Ki-67 were examined immunohistochemically in 43 cases of oral leukoplakia with or without epithelial dysplasia. The subjects were categorized as: none, 13 cases; mild dysplasia, 5 cases; moderate dysplasia, 17 cases; and severe dysplasia, 8 cases. The expression of these molecules in normal oral epithelia (22 cases) was also investigated. RESULTS: Strong syndecan-1 expression was observed on the surface of keratinocytes in normal epithelium. Immunopositivity was lost gradually as the extent of epithelial dysplasia increased. In normal epithelium, p53 and Ki-67 appeared mainly in the basal cell layer, while they were more widely distributed in leukoplakia. Specifically, significant changes were observed in the labeling index of p53 and Ki-67 in leukoplakia as epithelial dysplasia progressed from mild to moderate or severe. CONCLUSION: Our results reveal that overexpression of p53 protein and Ki-67 antigen, and down-regulation of syndecan-1 expression in the lower part of the epithelium, are associated with dysplastic changes. Therefore, the down-regulation of syndecan-1 expression may be the most important reliable marker for dysplastic changes.     

Oral leukoplakias with different degrees of dysplasia: comparative study of hMLH1, p53, and AgNOR

J Oral Pathol Med (2011) 40 : 305–311 Background: hMLH1 is one of the major proteins of the mammalian mismatch repair system. It has been suggested that the mismatch repair machinery could be linked to p53, a tumor suppressor protein. The AgNOR technique is used to assess cell proliferation. The aim was to compare the immunoexpression of hMLH1 and p53, and AgNOR number in oral leukoplakias with different degrees of dysplasia. Methods: Sixty‐two samples were evaluated by immunohistochemistry for hMLH1 and p53, and AgNOR technique, being 17 without dysplasia, 19 with mild dysplasia, 16 with moderate dysplasia, and 10 with severe dysplasia. Results: hMLH1 immunoexpression showed decreasing indexes, while p53 and AgNOR showed increasing indexes from lesions with lower degrees of dysplasia to lesions with more severe dysplasia. An inverse correlation between hMLH1 and both p53 and AgNOR, and a direct correlation between p53 and AgNOR were observed. Conclusions: Alterations in the immunoexpression pattern of hMLH1 and p53 seemed to be early events in oral carcinogenesis. During acquisition of a more dysplastic phenotype, keratinocytes may show diminished capacity of DNA repair and tumor suppression, as well as higher cellular proliferation, and these pathways can be somehow interconnected.     

Flow cytometer analysis of oral premalignant lesions: a pilot study and review

In a retrospective study, we examined 34 premalignant lesions of the oral cavity by flow cytometer analysis on formalin-fixed, paraffin-embedded tissue submitted to the University of Tennessee, Memphis, Oral Pathology Laboratory. Three categories of oral epithelial dysplasia were represented (eight mild, seven moderate, nine severe), as well as five epithelial hyperplasias without dysplasia and five fibrous nodules as controls. The DNA index and total proliferative index of each case were calculated. The objective of the study was to determine the amount of epithelial dysplasia necessary in oral lesions before DNA aneuploidy or high proliferative index is detectable and thus determine if flow cytometric analysis can be a diagnostic adjunct for oral premalignant lesions. The results showed that some cases in both the control and dysplastic categories exhibited a high total proliferative index (control = 1, no dysplasia = 1, mild dysplasia = 3, moderate dysplasia = 2, severe dysplasia = 2), whereas only the dysplastic lesions had an abnormal DNA index [8 of 24 (33%)]. The results indicate that flow cytometric analysis may have some limited potential as a diagnostic adjunct in oral premalignant lesions.     

RB1CC1在人和小鼠口腔癌发生发展中表达的比较研究

目的:比较视网膜母细胞瘤RB1-诱导卷曲蛋白1(RB1CC1)在人和小鼠正常口腔黏膜、上皮异常增生组织及口腔鳞状细胞癌中的表达,并探讨其在口腔癌发生发展过程中的作用。方法:采用免疫组化和RT-PCR检测人及小鼠在正常口腔黏膜、上皮异常增生、高分化鳞癌原发灶组织中RB1CC1蛋白及基因的表达情况。结果:RB1CC1蛋白在人上皮异常增生组、高分化鳞癌组的阳性表达高于正常组(P<0.05);RB1CC1蛋白在鼠正常组、异常增生组、高分化鳞癌组阳性表达逐渐增加,差异均有统计学意义(P<0.05)。人RB1CC1 mRNA的表达量在异常增生组与高分化鳞癌组无明显差异,正常口腔黏膜组均高于异常增生组与高分化鳞癌组(P＜0.05);小鼠RB1CC1 mRNA的表达量在正常口腔黏膜组与异常增生组、高分化鳞癌组差别无统计学意义。结论:RB1CC1表达在人和小鼠相似, RB1CC1可能参与了口腔鳞癌的早期癌变过程。     

p53 AND MDM2 PROTEIN EXPRESSION IN ACTINIC CHEILITIS

Actinic cheilitis is a potentially malignant lip lesion caused by excessive and prolonged exposure to ultraviolet radiation, which can lead to histomorphological alterations indicative of abnormal cell differentiation. In this pathology, varying degrees of epithelial dysplasia may be found. There are few published studies regarding the p53 and MDM2 proteins in actinic cheilitis. Fifty-eight cases diagnosed with actinic cheilitis were histologically evaluated using Banóczy and Csiba (1976) parameters, and were subjected to immunohistochemical analysis using the streptavidin-biotin method in order to assess p53 and MDM2 protein expression. All studied cases expressed p53 proteins in basal and suprabasal layers. In the basal layer, the nuclei testing positive for p53 were stained intensely, while in the suprabasal layer, cells with slightly stained nuclei were predominant. All cases also tested positive for the MDM2 protein, but with varying degrees of nuclear expression and a predominance of slightly stained cells. A statistically significant correlation between the percentage of p53 and MDM2-positive cells was established, regardless of the degree of epithelial dysplasia. The expression of p53 and MDM2 proteins in actinic cheilitis can be an important indicator in lip carcinogenesis, regardless of the degree of epithelial dysplasia.     

Putative cancer stem cell marker expression in oral epithelial dysplasia and squamous cell carcinoma

Multifactorial conditions underlie progression of potentially malignant oral lesions (PMOL) to oral squamous cell carcinoma (OSCC) and there is currently need for better prediction of malignant transformation. The hypothesised existence of cancer stem cells in dysplastic oral tissues provides the potential for more informed assessment of PMOL progression. Semi‐quantitative immunohistochemical assessment of four putative cancer stem cell markers (CD24, CD44, CD271 and ALDH1) was conducted with a training cohort of 107 patient biopsies to establish clinically applicable score threshold values that were subsequently applied to a blind diagnosis in an independent validation cohort of 278 biopsies. Stain intensity scores for ALDH1, CD24 and CD44, but not CD271 were greater for OSCC than normal tissues. The intensity of ALDH1 and CD24 immunostaining correlated with increased oral epithelial disease severity, and CD24 was effective in distinguishing OSCC from non‐malignant tissues, correctly diagnosing 71% of OSCC cases in the validation cohort. Importantly, CD24 immunostaining was effective in diagnosing the presence of dysplasia, correctly discriminating 69% of dysplasia tissues from normal tissues, although no distinction between mild and severe grades of dysplasia was achieved. The results highlight CD24 immunostain intensity as an effective marker of oral dysplasia and OSCC. In conclusion, CD24 immunostain intensity scoring may serve as a helpful technique to assist with the histological recognition of dysplasia in oral biopsies, but not for distinguishing between grades of dysplasia.