Chromosome 11 aneusomy in esophageal cancers and precancerous lesions- an early event in neoplastic transformation: An interphase fluorescencein situhybridization study from south India

Abstract

which may play a role in the neoplastic transformation of esophageal precancerous lesions to cancers. INTRODUCTIONMore than 30% of the adult population exhibits upper gastrointestinal tract disorders associated with symptoms such as regurgitation, heartburn and dysphagia, warranting an endoscopic evaluation. Some of these esophageal pathologies require medication while others can be managed by altering life-style and dietary habits. A certain percentage of these, however, progress into esophageal malignancies. In India, esophageal cancer is the second leading cancer in men and fourth leading cancer in women [1] . Epithelial tumors of the esophagus [squamous cell carcinoma (SCC) and adenocarcinoma (ADC)] are responsible for more than 95% of all esophageal carcinomas. This malignancy presents generally as a locally advanced disease, hence leading to poor prognosis with an average 5-year survival of < 12% in India [2] . Abnormal proliferation of the esophageal epithelial cells with hyperplasia and dysplasia in the normal squamous lining are regarded as premalignant lesions [3,4] . Another common premalignant condition is Barrett's esophagus (BE), where patients have a forty-fold increased risk for developing adenocarcinoma as compared to normal individuals. Although significant advances have been made in the diagnosis and treatment of esophageal carcinomas, not many studies have evaluated markers in the target tissue, in association with increased risk for malignant Abstract AIM: To detect aneusomic changes with respect to chromosome 11 copy number in esophageal precancers and cancers wherein the generation of cancer-specific phenotypes is believed to be associated with specific chromosomal aneuploidies. METHODS:We p e r fo r m e d f l u o r e s c e n c e i n s i t u hybridization (FISH) on esophageal tissue paraffin sections to analyze changes in chromosome 11 copy number using apotome-generated images by optical sectioning microscopy. Sections were prepared from esophageal tumor tissue, tissues showing preneoplastic changes and histologically normal tissues (control) obtained from patients referred to the clinic for endoscopic evaluation. RESULTS:Our results demonstrated that aneusomy was seen in all the cancers and preneoplastic tissues, while none of the controls showed aneusomic cells. There was no increase in aneusomy from precancers to cancers. CONCLUSION:Our results suggest that evaluation of chromosome 11 aneusomy in esophageal tissue using FISH with an appropriate signal capture-analysis system, can be used as an ancillary molecular marker predictive of early neoplastic changes. Future studies can be directed towards the genes on chromosome 11,

Role of Human papilloma virus Infection and Altered Methylation of Specific Genes in Esophageal Cancer

“…High frequency of chromosomal aneuploidy, attributed to an impaired Aurora A gene reported in many cancers, was also seen in esophageal cancers and precancers as reported from our group (Marumoto et al, 2003;Mohan et al, 2007). It has been suggested that p53 interacts with Aurora-A to suppress its oncogenic activity in a transactivation-independent manner (Chen et al, 2002).…”

Recent Advances in In Vivo Genotoxicity Testing: Prediction of Carcinogenic Potential Using Comet and Micronucleus Assay in Animal Models

“…Measurement of DNA damage using genotoxicity assays has been known as a crucial approach for understanding the carcinogenesis and assessing the risk of cancer incidence. 22 , 23 This review will discuss the significance of in vivo comet assay and in vivo MN assay for testing genotoxicity and predicting carcinogenic potential ( Fig. 1 ).…”

Allelic loss and mutations in a new ETRG-1 gene are early events in diethylstilbestrol-induced renal carcinogenesis in Syrian hamsters

“…For example, hTERT expression together with loss of heterozygosity (LOH) represent early events in lung carcinogenesis, as both were detected in precancerous lesions and in normal epithelium of heavy smokers (Capkova et al, 2007). Presence of chromosome 11 aneusomy in esophageal cancers and pre-cancerous lesions has been reported as an early event in neoplastic transformation (Mohan et al, 2007). Based on the finding of loss of heterozygosity (LOH) of RPL14 that was common in the dysplasia (preneoplastic lesions), malignant tissues and histologically normal epithelia, this genetic change has been reported as an early event in the tumorigenesis of esophagus (Huang et al, 2006).…”