| Abstract |
Cervical and endometrial cancers represent leading causes of female genital cancer. Surgery, chemotherapy and radiation treatment is the standard therapeutic tool for the management of female cancer. Radiotherapy is the most effective conservative treatment for cervical cancer while in the case of endometrial cancer it is reserved for women for whom the risks of surgery are high. The collaboration of many genetic factors, mutations and genetic multiformity in female genital cancer carcinogenesis shows the possible relation of these genetic factors with the prognosis and the effectiveness of radiotherapy. Thus, the effectiveness of radiotherapy may be affected from the genetic features of cancer cells target. The main scope of this study was the identification of molecular prognostic factors for the response in radiotherapy of cervical and endometrial cancer. Using microsatellite DNA analysis, we investigated 31 markers, located on 1, 2, 3, 9, 13 and 17 chromosomes. In particular, they are located in the following chromosomal sites: 1p, 2p, 2q, 3p, 9p, 9q, 13q, 17p and 17q. Specimens were from patients with cervical or endometrial cancer that were hospitalized in Obstetric-Gynecology Dept of University Hospital of Crete from March 1997 to May 1999. These patients underwent a definite therapeutic protocol and close follow up. We tried to identify any possible relation between clinico-pathology parameters and genetic alterations in genetic loci we studied. Statistical calculations were carried out in order to find out the relationship between the presence and absence of genetic alterations and the response to radiotherapy. Genetic alterations of the initial tumor genotypes were observed after radiation in 86.5% of cervical and 81.0% of endometrial cases. Reversions to the original normal genotype were observed in 40.5% and 28.6% respectively, predominantly in cured patients rather than in recurred cases. Survival curves by the Kaplan-Meier method showed a worse prognosis for cervical cancer patients whose tumors harbor allelic imbalance (AI) on 3p or 13q, and for endometrial cancer patients whose tumors harbor AI on 13q. Our data suggest a possible association of the hMLH1 or BRCA2 genes, implicated in distinct DNA repair pathways and located on 3p and 13q respectively, with response of cervical and endometrial cancer to radiotherapy. Moreover, microsatellite DNA analysis before and after radiation treatment could be used as a marker of the clinical outcome of patients.
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Η ανίχνευση των μεταλλάξεων του μικροδορυφορικού DNA σε γυναικολογικούς καρκίνους που έχουν υποβληθεί σε ακτινοθεραπεία
