Ki67 and Topoisomerase IIa comparative protein expression in colon adenocarcinoma

Postgraduate Thesis uoadl:2838832 251 Read counter

Κατεύθυνση Χειρουργική Ογκολογία
Library of the School of Health Sciences
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Niotis Athanasios
Supervisors info:
Πολυμενέας Γεώργιος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ, Επιβλέπων
Φραγκουλίδης Γεώργιος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Θεοδοσόπουλος Θεοδόσιος, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Original Title:
Συγκριτική μελέτη έκφρασης δεικτών κυτταρικού πολλαπλασιασμού Ki67 και Topoisomerase IIa στο αδενοκαρκίνωμα του παχέος εντέρου
Translated title:
Ki67 and Topoisomerase IIa comparative protein expression in colon adenocarcinoma
Ki-67 gene located on chromosome 10 (10q25) encodes a protein which is expressed in the nucleolus in all cell cycle phases except Go (arrest phase). In fact, Ki-67 expression increases as a cell progresses through the cell cycle, with highest expression being seen in G2/M phase cells. Concerning colon adenocarcinoma, Ki-67 is frequently overexpressed, but its prognostic significance is under investigation. Alternatively, there is an increasing use of some other proteins for evaluating cell proliferation rates, such as topoisomerases5.
Topoisomerases are a class of nucleic enzymes, which affect the topological structure of DNA. The main members of the family are Topoisomerase I (gene location 20q11), Topoisomerase II alpha (Topo IIa – gene location 17q21) and Topoisomerase IIb (gene location 3p24). Topo IIa and b isomers’ combined action promotes temporarily cutting and rejoining the DNA double helix. Winding and unwinding of the DNA double strand is a critically important molecular mechanism for replication, transcription and repair of chromosome structure.
Topo IIa, with a molecular mass of 170 kDa, is expressed in proliferating cells in late S phase with a peak in G2/M phases, where it is believed to be the primary mediator of
chromosome condensation. Correlating Ki-67 to Topo IIa duration of expression, Topo IIa protein level seems to provide a better estimation of the number of actively proliferating cells and for this reason it could be used as a reliable marker of proliferation. Furthermore,
topoisomerases inhibition promotes cell death and for this reason they are targets for specific chemotherapy. Some clinical studies have shown that adjuvant chemotherapy based on a
combination of anthracyclines (doxorubicin, etoposide) and fluorouracil/cyclophosphamide
or carboplatin/paclitaxel is very effective in patients with breast, endometrial or also ovarian
In the current study we will focus on co-expression of the two proliferation markers in twenty-five (n=25) cases of colon adenocarcinoma analyzed by IHC. Digital image analysis assay (DIA) will be performed for evaluating the results (Nuclear Labeling Index-NLI).
Survival analysis based on a variety of clinic-pathological parameters will also be implemented.
Main subject category:
Health Sciences
Ki67, Topoisomerase IIa, Colon adenocarcinoma
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