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Cervical cancer screening by enhanced cytology: application of novel markers

2014-12-13 00:01:36

Hong Kong Medical Journal; DEC 2014; Volume 20 Number 6 (Supplement 6)



ANY Cheung, XY Guan, HYS Ngan



Introduction



Cervical cytological examination is the most widely applied screening method for cervical cancer and its precursors. Liquid-based cytology produces good-quality smears and enables the use of ancillary laboratory techniques to distinguish neoplastic from benign cells.



Immunohistochemical and molecular markers have been tested to identify dysplastic cells in cervical smears. When testing for human papillomavirus (HPV) or chromosome aneusomy, MIB1 (Ki67) and p16 immunocytochemistry helps to highlight dysplastic or cancer cells. Such markers may be useful for triage of patients with borderline smears of atypical squamous cells of undetermined significance (ASCUS), which is the most common abnormal cytological finding and is associated with a significantly higher risk of developing cervical cancer and its high-grade precursors.



In this study, immunocytochemical markers (p63, p73, Eif-5A2, and DJ-1 genes) were tested in cervical cancer screening using immunocytochemistry and chromogenic in situ hybridisation. Differential expression of these genes in cervical cytology is useful in diagnosing cervical cancer.



p63 and p73 genes are members of the p53 family and play important roles in carcinogenesis. Different isoforms of p63 and p73 can enhance or suppress neoplastic cell growth. Differential
expression of p63 and p73 isoforms was reported in normal and neoplastic cervical epithelium. p73 expression is associated with radiosensitivity of cervical cancer. In a study of frequently amplified regions at 3q26.2, Eif-5A2 was found to be important in ovarian carcinogenesis. Similar regions at chromosome 3q have also been identified in cervical cancer. Eif-5A2 is a potential marker for cervical cancer. DJ-1 has been identified as a suppressor of PTEN, which is a tumour suppressor gene. DJ-1 overexpression has been noted in human malignancies compared with healthy tissue.



Novel genes can be identified in specific chromosome regions by array comparative genomic hybridisation. In our previous studies on cervical cancer samples and cell lines, the frequently
amplified regions were 1q, 3p, 3q, and 5p. Besides Eif-5A2, eight gene loci can be identified and the amplification status can be detected by chromogenic in situ hybridisation. This study aimed to assess the application value of adjunct markers in liquid-based cervical cytology for detection of carcinoma cells and precursors.



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