Značaj serumske izoforme prostata specifičnog antigena i njegovih derivata u ranom otkrivanju karcinoma prostate
The role of the serum isoform of the prostate specific-antigen and its derivatives in early detection of prostate cancer
Doktorand
Vuković, Ivan I.Mentor
Vuksanović, AleksandarČlanovi komisije
Đorđević, MiroslavBojanić, Nebojša
Mićić, Sava
Metapodaci
Prikaz svih podataka o disertacijiSažetak
Karcinom prostate (CaP) je najčešći malignitet kod muškaraca preko 70 godina u zemljama
Severne i Zapadne Evrope, kao i SAD. U Srbiji, CaP je na trećem mestu po učestalosti i na
trećem mestu po mortalitetu. Na globalnom nivou, CaP je drugi po učestalosti od svih karcinoma
i šesti uzrok smrti od karcinoma. Svi ovi epidemioški podaci pokazuju koliko je CaP veliki
zdravstveni i ekonomski problem, kako u celom svetu, tako i u Srbiji. Povećanje incidence CaP
posledica je široke primene prostata specifičnog antigena (PSA) testiranja koje je kasnih
osamdesetih godina dovelo do revolucionarnih promena u dijagnostici CaP. MeĎutim, kako je
PSA organ specifičan, ali ne i karcinom specifičan marker, on se ne može smatrati idealnim
markerom.
Kako bi se poboljšala specifičnost PSA za detekciju CaP, vremenom su uvoĎeni novi derivati
PSA, kao što su dinamika rasta PSA u funkciji vremena (eng. PSA velocity, PSAV), odnos
ukupnog PSA i zapremine prostate (eng. PSA densitiy, PSAD), udvostručenje bazične v...rednosti
PSA tokom vremena (eng. PSA doubling time), procentualni odnos slobodnog prema ukupnom
PSA (%fPSA). Pokazano je da jedino %fPSA donekle poboljšava specifičnost PSA za rano
otkrivanje CaP. Brzo se javila potreba za pronalaženjem boljih i osetljivijih biomarkera koji bi sa
većom sigurnošću mogli da ukažu na CaP. Pokazalo se da su serumska izoforma prostata
specifičnog antigena p2PSA i njegovi derivati %p2PSA, PHI (eng. prostate health index),
najbolji novi biomarkeri koji značajno povećavaju specifičnost PSA za detekciju karcinoma
prostate. Što je važnije, ovi biomarkeri mogu da naprave razliku izmeĎu klinički
nesignifikantnog, nisko-rizičnog tumora i njegove agresivne forme. Njihovom primenom
značajno se smanjuje broj pacijenata koji podležu suvišnim dijagnostičkim i terapijskim
procedurama (eng. overdiagnosis & overtreatment) kao i svim komplikacijama koje ih prate.
MeĎusobni matematički odnosi p2PSA, fPSA i ukupnog PSA dat je formulom čiji rezultat
označava PHI (PHI = [p2PSA / fPSA] × PSA1/2), a meĎusobni odnos p2PSA i fPSA, odnosno
%p2PSA formulom (p2PSA/fPSA x 100)...
Prostate cancer (PC) is the most common malignancy in men aged >70 in Western and Eastern
European Countries, as well as in the US. In Serbia, PC is the third most common incidence rate
and has the third most common mortality rate. On a global scale, PC takes second place of most
common incidence in all malignancies, and sixth place for most common reason of mortality on
all Carcinomas. All these epidemiological data indicate that PC is a significant health and
economic issue, not only globally, but also in Serbia. The increase of PC is a consequence from
high use of prostate specific antigen (PSA) assessment, which led to revolutionary changes in the
diagnostics of PC in the late eighties. However, as the PSA is organ specific, but not also
carcinoma specific marker, it cannot be considered as an ideal marker.
Overtime, in order to improve the specificity of PSA for PC detection, new derivates of PSA
were introduced, such as PSA velocity (PSAV), PSA densitiy (PSAD), PSA duobling time,... the
percentage of free versus total PSA (%fPSA). Only %fPSA has been proved to in some extent
increase the specificity of PSA in regards to early discovery of PC. In a short time, the search for
a better and more sensitive marker appeared, which would be able to indicate PC with a higher
determination. It was shown that the serum isoform of the prostate specific antigen p2PSA and
its derivates %p2PSA, PHI (Prostate health index), are the best of newer biomarkers that
significantly increase the specificity of PSA in detecting PC. More importantly, these biomarkers
can make the difference between the indolent, clinically non significant tumor and it's aggressive
form which needs to be treated. Including these in diagnostic procedures significantly decreases
number of patients that are undergoing unnecessary diagnostic and therapeutic procedure
(overdiagnosis and overtreatment) as well as complications due to the same. The mathematic
algorithm incorporating p2PSA, fPSA and total PSA is given by the formula which results in
PHI (PHI = [p2PSA / fPSA] × PSA1/2), whereas the correlation between p2PSA and fPSA, e.g.
%p2PSA formula (p2PSA/fPSA x 100)...