Identification and clinical Application of the Genes Associated with Carc nogenesis of the Uterine Cervix

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(1)Identification of the genes associated with carcinogenesis of the uterine cervixWe showed overexpression of the TSC403 gene was a late event in cervical carcinogenesis, and that TSC403 was associated with invasion and metastasis of cervical carcinoma. Cervical carcinomas with overexpression of TSC403 were demonstrated to have significantly poorer prognosis than those without overexpression (p<0.05).We also identified 20 genes and ESTs specifically upregtdated or down-regulated in cervical carcinoma compared with normal cervical tissue by gene expression profiling study using DNA microarray. As one of the 20 gene and ESTs, IGFBP-5 was demonstrated to be expressed in the keratinizing layer of normal cervical squamous epithelium specifically and to be suppressed in cervical carcinoma, implying that IGFBP-5 is associated with proliferation or differentiation in cervical carcinogenesis.We showed that monoclonal or highrisk type HPV-infected GINs were more likely to progress or persist th … More an polyclonal or high-risk type HPV-negative ones (p=0.009 for monoclonal vs. polyclonal, p=O.O24 for high-risk type HPV positive vs. negative). Moreover, the combination of clonal status and high-risk type HPV infection were demonstrated to be significantly correlated with clinical outcome (p=0.003). These facts show clonal status and high-risk type HPV infection are useful biomarkers predicting the outcome of CIN.(3)Identification of the genes characterizing Minimal Deviation Adenocarcinoma (MDA) of the cervixLKB1 has been identified as the tumor suppressor gene responsible for Peutz-Jeghars Syndrome (PJS). We showed somatic mutations of the LKB1 gene occurred in 6 (55%) of 11 MDAs and that MDAs with LKB1 mutations had significantly poor prognosis than without the mutaions (p<0.05). We also demonstrated Pylolic gland metaplasia of the uterine cervical glands, resembling MDAs in histopathology, were able to be ruled out in the points that the composition of the lesions were polyclonal and had no mutations of LKB1. Less