CHEK2, MCM3 and MSH6 may have a Potential Role as Molecular Markers of Screening in the Detection of Cervical Premalignant and Malignant Lesions: A Scoping Review
Keywords:
Liquid based cytology, Pap smear, Cervical cancer, CHEK2, MSH6, MCM3Abstract
Lesions of the uterine cervix, including neoplasia, are the foremost cause of female deaths worldwide. Cervical malignancy ranks as the third most common gynecological malignancy globally, with an increasing prevalence reported in Asia each year. Early detection through cytology-based screening makes it one of the most preventable forms of malignancy. This review was planned to investigate the potential role of CHEK2, MCM3, and MSH6 in detecting cervical lesions. Therefore, a scoping review involved searching for published articles on databases such as PubMed, MEDLINE, EMBASE, and the Cochrane Library. According to the searched literature, several genes contribute to cervical cancer occurrence. The CHEK2 gene acts as a tumour suppressor by regulating the cell cycle pathway. At the same time, the loss of function of MSH6 leads to high rates of mutations in microsatellites, thereby deactivating the mismatch repair pathway. Moreover, the MCM3 gene's helicase activity in cell cycle regulation is overexpressed in various malignant tissues and cancer cell types. Tumor microsatellite instability (MSI) indicates the loss of mismatch repair function, which is seen in cervical cancer and reported in many other tumors. Expression of these genes may be associated with the "abnormality of the epithelial cell" term in the Bethesda system for classifying cervical lesions on cytology, ranging from atypical squamous cells to low-grade and high-grade dysplasia, which can potentially lead to invasive squamous cell carcinoma linked to transient HPV infection. Due to the scarcity of local data regarding the role of these genes in cervical malignancy, further research is crucial.
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