口腔白斑组织癌变标志性基因筛查

口腔黏膜白斑病（oral leukoplakia,OLK）是最常见的口腔粘膜的癌前病变．OLK恶性转化率高达43%,因此加强其风险调查和监测对于该病的预防和治疗具有重要意义．本研究采用美国SuperArray公司的肿瘤基因芯片（OHS-802）检测口腔正常组织、OLK组织和口腔鳞状细胞癌（oral squamous cell carcinoma, OSCC)组织的肿瘤相关基因表达差异,旨在筛查与口腔黏膜白斑病发生和癌变相关的表达阳性基因,为探究OLK的发生及癌变机制奠定基础．将“正常组织→OLK组织→OSCC组织”连续递增2倍以上或递减2倍以上的基因确定为OLK组织癌变的标志性基因．SuperArray基因芯片、RT-PCR法和实时定量PCR结果显示,仅有3个基因（ACP-2、BCL-2、SOCS-3）表达水平连续下调2倍以上,有6个基因（CLK-3、CTNNB-1、FKBP-8、GDF-15、NF-1、XRCC-1）表达连续上调2倍以上．进一步经RT-PCR和实时定量PCR验证,其结果与SuperArray结果一致．本研究结果提示,ACP-2等9个基因可能是口腔正常黏膜组织经OLK转变为癌组织的驱动基因,可作为OLK组织、OSCC组织和口腔正常黏膜组织诊断的分子标志．     

Correlation of Trace Elemental Profiles in Blood Samples of Indian Patients with Leukoplakia and Oral Submucous Fibrosis

In order to ascertain possible correlation between alterations in trace elemental profile and the progression or regression of two most common potentially malignant disorders affecting oral cavity, namely oral submucous fibrosis and leukoplakia, blood from 60 patients from each group of patients as well from 30 healthy individuals was analyzed for elemental profiling employing EDXRF technique. Out of the 16 detected elements (K, Si, Ca, V, Cr, Ni, Mn, Fe, Cu, Zn, Se, Br, Rb, Sr, Co, and Pb), Mn, Fe, Zn, Br, and Co showed remarkable alteration in their profile in both leukoplakia and oral submucous fibrosis patients with respect to the normal healthy individuals. While Zn, Br, and Fe reflected similar changes--showing gross depletion in both the diseased groups, Mn and Co depicted inverse pattern of alterations in their concentrations in the two types of precancerous disorders when compared to the control subjects.     

Risk Stratification of Oral Potentially Malignant Disorders in Fanconi Anemia Patients Using Autofluorescence Imaging and Cytology-On-A Chip Assay

Fanconi anemia (FA) is a hereditary genomic instability disorder with a predisposition to leukemia and oral squamous cell carcinomas (OSCCs). Hematopoietic stem cell transplantation (HSCT) facilitates cure of bone marrow failure and leukemia and thus extends life expectancy in FA patients; however, survival of hematologic malignancies increases the risk of OSCC in these patients. We developed a “cytology-on-a-chip” (COC)–based brush biopsy assay for monitoring patients with oral potentially malignant disorders (OPMDs). Using this COC assay, we measured and correlated the cellular morphometry and Minichromosome Maintenance Complex Component 2 (MCM2) expression levels in brush biopsy samples of FA patients’ OPMD with clinical risk indicators such as loss of autofluorescence (LOF), HSCT status, and mutational profiles identified by next-generation sequencing. Statistically significant differences were found in several cytology measurements based on high-risk indicators such as LOF-positive and HSCT-positive status, including greater variation in cell area and chromatin distribution, higher MCM2 expression levels, and greater numbers of white blood cells and cells with enlarged nuclei. Higher OPMD risk scores were associated with differences in the frequency of nuclear aberrations and differed based on LOF and HSCT statuses. We identified mutation of FAT1 gene in five and NOTCH-2 and TP53 genes in two cases of FA patients’ OPMD. The high-risk OPMD of a non-FA patient harbored FAT1, CASP8, and TP63 mutations. Use of COC assay in combination with visualization of LOF holds promise for the early diagnosis of high-risk OPMD. These minimally invasive diagnostic tools are valuable for long-term surveillance of OSCC in FA patients and avoidance of unwarranted scalpel biopsies.     

Risk Stratification in Young Patients With Channelopathies

Identifying the young patient at risk of malignant arrhythmias and sudden cardiac death remains a challenge. It is increasingly recognised that sudden death, syncope and aborted cardiac arrest at a young age in patients with a structurally normal heart may be the result of various ion channel disorders - the channelopathies. The approach to risk stratification involves a combination of the clinical presentation, taken in conjunction with the family history, genetic testing, invasive electrophysiological studies or other provocative tests where appropriate and feasible. A logical approach to risk stratification in some of the commoner channelopathies seen in paediatric practice is presented.     

MACC1和C-Met在口腔白斑和口腔鳞状细胞癌中的表达及意义

目的:探讨分析MACC1和C-Met在正常口腔黏膜、口腔白斑及口腔鳞状细胞癌中的表达及其临床意义。方法:采用免疫组化SP法检测20例口腔黏膜、20例上皮异常增生白斑、50例口腔鳞癌组织中的MACC1、C-Met蛋白的表达情况,采用X2和spearman等级相关分析对结果进行判定。结果:MACC1、C-Met蛋白在异常增生型白斑和口腔鳞癌中的阳性表达率分别为50%、76%,35%、66%,均明显高于正常口腔黏膜(17.6%,5.0%),差异均有统计学意义(P0.05)。MACC1和C-Met蛋白表达与口腔鳞癌的分期、淋巴结转移及分化程度密切相关(P0.05)。Spearman等级相关分析显示口腔白斑及口腔鳞癌中MACC1和C-Met的表达呈现正相关(P0.05)。结论:MACC1和C-Met在上皮不典型增生性白斑和口腔鳞癌中高表达,二者在口腔黏膜白斑的癌变和口腔鳞癌的发生发展中可能起重要作用。