Prognostic significance of <i>PTEN</i>, <i>RB1</i> and <i>BRCA2</i> gene loss in patients with localized and locally advanced prostate cancer

Abstract

Background. Prostate cancer is the most common malignant condition among oncological diseases of the genitourinary tract, which occupies the second place in male mortality from malignant neoplasms. At the same time, population of patients with prostate cancer is heterogeneous: in some patients, the disease does not require active treatment, while in others it progresses rapidly with the formation of metastatic castration-resistant prostate cancer. Therefore, the search for new predictive markers remains relevant.Objective. Analysis of the prognostic significance of the loss of heterozygosity of PTEN, RB1, TP53, BRCA1 and BRCA2 genes in patients with localized and locally advanced prostate cancer.Materials and methods. The study included 52 patients with prostate cancer, 31 (59.6 %) of whom had a localized form (T1-2N0M0), and 21 (40.4 %) - locally advanced (T3a-bN0/1M0). All patients underwent radical prostatectomy, followed by genotyping of postoperative and biopsy specimens to determine genetic alterations in the studied genes. Detection of deletions in the studied genes was carried out using the method of multiplex ligation-dependent probe amplification.Results. In 13 (25.0 %) patients in the postoperative specimen was detected deletion of PTEN gene, in 6 (11.5 %) - deletion of RB1 gene, and in 1 (1.9 %) - deletion of BRCA2 gene. At the same time, patients with loss of PTEN heterozygosity were more likely to have perineural invasion (p = 0.01) and lymph node involvement (p = 0.0003). Deletion of RB1 gene is associated with more frequent detection of high-grade tumors (p = 0.013), cribriform growth component (p = 0.002), and invasion of the periprostatic tissue (p = 0.005).Conclusion. Detection of loss of heterozygosity of PTEN and RB1 genes is a promising tool for clarifying the prognosis of the disease, which in the future will allow more accurately stratify patients into risk groups for biochemical relapse.