| Abstract | Ciljevi istraživanja: Tumorske matične stanice (engl.cancer stem cells, CSCs) predstavljaju manji dio stanica u tumoru koje se mogu samoobnavljati i proliferirati, te su vjerojatno odgovorne za iniciranje i održavanje tumorskog rasta. CD133, CD117 i CD44 su najčešće korišteni biljezi za potencijalne CSCs, osobito za CSCs jajnika, no njihov klinički značaj još uvijek nije dovoljno istražen. Cilj ovog istraživanja bio je usporediti imunohistokemijski izražaj biljega CD133, CD117 i CD44 kod primarnog seroznog raka jajnika i pripadajućih peritonealnih metastaza, te ispitati njihov potencijalni prognostički značaj.
Ispitanici i metode: U istraživanje je uključeno 69 bolesnica s uznapredovalim seroznim rakom jajnika FIGO stadija III i IV (engl. International Federation of Gynecology and Obstetrics) sa svim potrebnim kliničkim podacima o operativnom i adjuvantnom liječenju, te praćenju bolesnica. Imunohistokemijskom metodom analizirani su tkivni rezovi primarnih tumora i pripadajućih peritonealnih metastaza. Izražaj ispitivanih biljega određivan je na velikom povećanju (x200), na deset slučajno odabranih vidnih polja, koja se međusobno ne preklapaju. Rezultat je izražen kao postotak pozitivnih stanica od ukupnog broja stanica u pojedinom vidnom polju.
Rezultati: Izražaj biljega CD133 uočen je u apikalnim/endoluminalnim dijelovima tumorskih stanica, u 58% tumora i 42% metastaza. Medijan postotka pozitivnih tumorskih stanica na CD133 u tumorima bio je 1 (0,1-7)%, a u metastazama 0,55 (0,1-6)%. Izražaj biljega CD117 uočen je kao citoplazmatsko i/ili membransko bojenje, a pronađeno je u 81% tumora i 77% metastaza. Medijan CD117 pozitivnih stanica u tumorima bio je 1 (0,1-8)%, a u metastazama 0,1 (0,1-6)%. U broju pozitivnih slučajeva i u postotku pozitivnih tumorskih stanica u tumorima i metastazama izražaj biljega CD133 i CD117 nije pokazao statistički značajnu razliku. Izražaj biljega CD44 uočen je kod 29% tumora i 46% metastaza kao membranski, a mjestimice i citoplazmatski pozitivitet. Medijan CD44 pozitivnih stanica u tumorima je 3 (1-26)%, a u metastazama 4 (1-36)%. Medijan postotka CD44 pozitivnih stanica veći je u uzorcima metastaza u odnosu na tumore i razlika je statistički značajna (P=0,006). Univarijatna analiza pokazala je da bolesnice s visokim izražajem biljega CD133 u tumoru imaju statistički značajno kraće vrijeme do pojave recidiva i vrijeme preživljenja (P = 0,004 odnosno P = 0,016). Bolesnice s visokim izražajem biljega CD117 u tumoru imaju statistički značajno kraće vrijeme do pojave recidiva bolesti (P = 0,034). Izražaj biljega CD44 nije pokazao statističku značajnost za pojavu recidiva i za preživljenje. Cox-ovom regresijskom metodom izražaj biljega CD133 u uzorcima tumora uočen je kao nezavisni prognostički čimbenik.
Zaključci: Naša studija pokazuje da imunohistokemijska ispoljenost biljega CD133 i CD117 može imati potencijalnu kliničku vrijednost u predviđanju progresije bolesti i prognoze kod seroznog raka jajnika. Biljeg CD44 nije pokazao prognostički značaj. Izražaj biljega CD133 se pokazao kao nezavisni prognostički čimbenik kod pacijentica sa seroznim rakom jajnika. |
| Abstract (english) | Objectives: The cancer stem cells (CSCs) represent a minority of tumor cells that are able to proliferate and self-renew and might be responsible for tumor initiation and maintenance. The CD133, CD117 and CD44 are the most commonly used markers for putative CSCs, especially for ovarian CSCs, but its clinical significance remains uncertain. The aim of this study was to compare the immunohistochemical expression of CD133, CD117 and CD44 in primary ovarian serous carcinoma and peritoneal metastasis and to examine their potential prognostic significance.
Patients and Methods: The study included 69 patients diagnosed with ovarian serous carcinoma (FIGO, engl. International Federation of Gynecology and Obstetrics; stage III or IV). The study included a retrospective collection of archival samples and clinical information of the patients. All patients underwent primary surgery followed by chemotherapy. Patients records were reviewed and clinicopathological characteristic as well as follow-up data were noted. The primary epithelial ovarian cancer samples and their peritoneal metastasis samples were immunohistochemicaly stained for CD133, CD117 and CD44 proteins. The positive stained cells were counted in ten random and non overlapping fields at high magnification (x200). The results were expressed as the percentage of total number of cells counted in the same fields.
Results: CD133 expression was mainly seen in the apical/endoluminal cell surface of tumor cells and was found in 58% of carcinoma samples and 42% of metastasis. The median of CD133 positive cells in tumors was 1 (0.1-7) %, and in metastases was 0.55 (0.1-6) %. CD117 expression appeared as a cytoplasmic and/or membranous stain and was found in 81% of carcinoma samples and 77% of metastasis. The median of CD117 positive cells in tumors was 1 (0.1-8) %, and in metastases was 0.1 (0.1-6) %. The number of positive cases and the percentage of positive tumor cells in tumors and metastases for CD133 and CD117 did not show a statistically significant difference. CD44 expression appeared as membranous and sporadically as cytoplasmic stain in 29% of carcinoma samples and 46% of metastasis. The median of CD44 positive cells in tumors was 3 (1-26) %, and in metastases was 4 (1-36) %. The median percentage of positive cells was higher in metastases samples in relation to tumors samples and difference was statistically significant (P = 0.006). Univariate analysis showed that patients with high CD133 expression in tumor have significantly shorter time to progression and time to survival (P=0.004 and P=0.016, respectively). Patients with high CD117 expression in tumor have significantly shorter time to progression (P=0.034). The expression of CD44 did not reach statistical significance for recurrence and survival. Cox´s proportional hazards model identified expression of CD133 protein in tumor as independent prognostic factor.
Conclusion: Our study indicates that the immunohistochemical assessment of CD133 and CD117 expression may have potential clinical value in predicting disease progression and prognosis in serous ovarian cancer. The expression of CD44 showed no prognostic significance. CD133 proved to be an independent prognostic factor in serous ovarian cancer patients. |
