Serumski CA125 ukazuje na period bez bolesti i sveukupno preživljenje u bolesnica s karcinomom jajnika, no podatci o salivarnim vrijednostima CA125 su malobrojni. Prijašnja istraživanja pokazuju da komplentna krvna slika, amilaza, elektroliti i C-reaktivni protein (CRP) mogu odrediti prisutnost zloćudnosti, tijek bolesti i preživljenje bolesnica s karcinomima jajnika. Cilj istraživanja bio je usporediti salivarne i serumske vrijednosti CA125 u bolesnica s dobroćudnim i zloćudnim tumorima jajnika te ustanoviti, eventualnu, korelaciju između CA125 vrijednosti u serumu i slini. Cilj je bio usporediti vrijednosti kompletne krvne slike i CA125 s preživljenjem bolesnica. U 48 bolesnica s dobroćudnim i u 50 bolesnica sa zloćudnim tumorima jajnika su određeni leukociti, trombociti, kalij, amilaza, CRP i CA125, dok se iz sline određivao CA125. CA125 u slini i serumu određivao se uz pomoć enzimskoga imunotesta. Koncentracija serumskoga kalija i amilaze odredila se fotometrijom, a CRP imunoturbidimetrijom. Serumska analiza krvne slike radila se rutinskim metodama. Statistička analiza napravila se uz pomoć Kolmogorov–Smirnovljeva testa, Mann-Whitney U-testa i Kaplan-Meirove analize preživljenja te su vrijednosti manje od 0,05 smatrane znakovitima. Bolesnice sa zloćudnim tumorima jajnika imale su znakovito viši salivarni i serumski CA125, CRP, leukocite i trombocite te niži hemoglobin u odnosu na bolesnice s dobroćudnim tumorima jajnika. Znakovita korelacija serumskoga CRP-a i CA125 bila je u bolesnica sa zloćudnim tumorima jajnika. Znakovito povišene serumske vrijednosti CA125 i amilaze korelirale su s kraćim preživljenjem, dok su povišene vrijednosti salivarnoga CA125, hemoglobina i kalija znakovito korelirale s dužim preživljenjem. Zaključno, salivarni CA125 ima moguću primjenu u detekciji karcinoma jajnika.
|Abstract (english)|| |
Background and objectives: Malignant tumors are often accompanied by an increased risk of hematological abnormalities. Recent studies have shown that the presence of systemic inflammation correlates with poorer disease-free and overall survival in patients with cancer. Anemia, haemoglobinemia, thrombocytosis and leukocytosis are thought to be adverse prognostic factors in various malignancies. Thrombocytosis, leukocytosis and anemia have been demonstrated to be independent poor prognostic factors in ovarian, endometrial and uterine serous papillary carcinoma. It is known that over 20% of ovarian cancer patients have preoperative thrombocytosis or hyperfibrinogenemia. Furthermore, we assumed that salivary and serum CA125 levels might differentiate benign from malignant ovarian masses as salivary samples are easier to collect, cheaper and non-invasive.
Materials and Methods: Saliva was collected according to Wu Wang et al. over a five minute period into calibrated test tubes while participants were sitting, before 8-10 A.M. From one tube CRP, calcium and amylase were instantly determined in sera. CRP was determined by immunoturbidimetry, calcium and amylase by photometry, all on clinical chemistry analyzer, Architect c8000 (Abbott, Illinois, USA). The tumor marker CA125 in serum and in saliva was measured on automatic immunochemistry analyzer Immulite 1000 (Siemens Healthcare Diagnostics, Erlangen, Germany) with chemiluminescent enzyme immunometric method, using original Siemens reagents and adjustors according to the manufacturers' instructions. Calibration range for CA125 is 500 kIU/L with analytical sensitivity of 0,2 kIU/L. Statistical analysis included the Kolmogorov–Smirnov test, Mann-Whitney U-test, Spearman correlation analysis and Kaplan–Meier analysis. P < 0.05 was significant in all analyses.
Results: The group with malignant tumors was significantly older than the group with benign tumors (59.3±14.5 years versus 46.9±16.24 years, p<0.001) with significantly higher salivary CA125 levels (median (IQR), >500 (>500->500) towards >500 (252->500) kIU/L, p=0.017) as well as in serum (median (IQR), 491.7 (145.7-855.0) towards 28.1 (12.1-66.1) kIU/L, p<0.001) and CRP levels (median (IQR), 23.1 (7.2-62.6) towards 3.10 (1.35-4.85) mg/L, p<0.001). Also, in patients with malignant tumors, a significantly higher leukocyte and platelet count was found (p<0.001 for both) and lower haemoglobin level (p<0.001). Other parameters were comparable in both groups of patients (erythrocyte count, potassium levels,
sodium, chloride and calcium (p>0.05 for all of them) and amylase (p=0.537). The analysis of salivary and serum CA125 in patients with malignant tumors (N=44) showed the same pattern (R= 0.087, p=0.575, Spearman correlation analysis) of incompatibility in the entire sample, while in the group with benign tumors (N=47) a slight significance was obtained which was inversely related to the salivary and serum CA125 (R= -0.415, p=0.004, Spearman correlation analysis). The increase in the serum CA125 was correlated with decreased salivary CA125. Tables 4 and 5 show significant inverse correlation between serum CA125 and the age of the participants in the patients with benign and malignant tumors. In patients with benign tumors, there was an inverse correlation (R= -0.299, p=0.041), in patients with malignant tumors there was an inverse correlation with age (R= 0.307, p=0.034). In patients with benign tumors, there was a significant correlation of the salivary CA125 with the erythrocyte number (R=0.356, p=0.014) and correlation with haemoglobin values (R=0.351, p=0.016). In the group with malignant tumors there was a significant correlation of the serum CA125 with CRP (R=0.484, p<0.001). All obtained significant correlations were weak. Significantly independent predictive variables for overall survival were CA125 in the serum, salivary CA125, amylase, hemoglobin and potassium. The increase in serum CA125 for every kIU/L decreases overall survival for 0.1% (HR 1.001, p=0.013). Increase in salivary CA125 for every kIU/L increases the overall survival for 0.7% (HR 0.993, p=0.002). Increase in amylase for every U/L decreases the overall survival for 0.9% (HR 1.009, p=0.013). Increase in hemoglobin for every g/L increases the overall survival of 4% (HR 0.960, p=0.044). Increase in potassium levels for every mmol/L increases the overall survival for 78% (HR 0.320, p=0.017).
Conclusions: The results of this study showed that patients with malignant tumors were significantly older than ones with benign tumors, they also had significantly higher salivary and serum CA125 and CRP levels. Patients with malignant tumors also had significantly higher leukocyte and platelet count together with lower hemoglobin level. In patients with malignant tumors, there was a significant correlation of the serum CA125 with CRP. Significantly increased levels of serum CA125 and amylase correlated with decreased survival, while increased salivary CA125, hemoglobin and potassium levels significantly correlated with an increased survival. Salivary CA125 levels might indicate the presence of malignant ovarian tumors.