Κατεύθυνση Χειρουργική ΟγκολογίαLibrary of the School of Health Sciences
Πολυμενέας Γεώργιος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ, Επιβλέπων
Φραγκουλίδης Γεώργιος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Θεοδοσόπουλος Θεοδόσιος, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Συγκριτική μελέτη έκφρασης δεικτών κυτταρικού πολλαπλασιασμού Ki67 και Topoisomerase IIa στο αδενοκαρκίνωμα του παχέος εντέρου
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:
Ki67, Topoisomerase IIa, Colon adenocarcinoma