This dissertation is dedicated to determining the prognostic significance of disseminated tumor cells (DTCs), which are detected in bone marrow (BM) of patients with PCa, and markers associated with stem tumor cells – CD24 and CD44, which determine the phenotype of malignantly transformed tumor cells.
All patients with PCa were grouped into four groups, depending on the status of CD24 and CD44 in malignant transformed cells: CD24-, CD44- – 38 patients, CD24+, CD44- – 16 patients, CD24-, CD44+ – 39 patients, CD24+, CD44+ – 42 patients. It was important to find the relation between the variant expression profile of CD24 and CD44 in PCa tissue and the clinical characteristics of patients. It was found that patients whose tumors did not express CD24 and were positive for the marker CD44 (CD24-, CD44+), were at stage III and stage IV of disease, category N1, high score on Gleason scale (8-9) and the highest output PSA level – more than 18.8 ng / ml. Regardless of the type of primary treatment, patients whose tumors were CD24-, CD44+ had the most unfavorable course of the disease. Surgical treatment in the volume of radical prostatectomy in this cohort of patients statistically significantly increased the indicators of their overall three-year survival. The remission of the disease was most often observed in patients with tumors that were CD24+, CD44+ when applied to surgical treatment (46.3% of cases) and CD24 , CD44- (63.1% of cases) in patients undergoing hormone therapy.
It is established that patients with PCa who have DTCs detected in the BM and tumor cells along with the expression of CD44 do not express CD24 belong to the group with high risk of disease progression: disease progression was diagnosed in 40.8 % of patients, remission – in 2.3 % of patients. The most favorable clinical course is typical for patients who have no DTCs and no tumor cells expressing neither CD24 nor CD44 (26.7 % of patients). We have also revealed a tendency of the growing number of patients in remission among patients undergoing radical surgical treatment. An estimate of overall three-year survival showed that the number of patients who remained alive for 36 months was significantly higher among those who underwent surgery (92.3 % versus 11.1 % of patients after hormone therapy).
Thus, therapeutic tactics that involve the use of radical prostatectomy should be considered as a mandatory component of the primary treatment of patients with a high risk of recurrence of a neoplastic process who have such molecular and biological characteristics as DTCs in BM and phenotype of tumor cells CD24-, CD44+.
During the research we have also developed a mathematical model to quantify the likelihood of clinical course of PCa on the basis of generally recognized and newly proposed prognostic markers, the overall efficiency of which was 88.1% (sensitivity 92.9%, specificity – 79.6%), and for determination of lethal case occurrence probability – 97,0% (sensitivity 98,3%, specificity – 87,5%).
