Abstract
Introduction. Early diagnosis and personalized treatment of patients with malignant ovarian tumors based on molecular changes in the tumor of a specific patient is a priority research area in gynecological oncology. However, the clinical informativeness of certain genetic signatures remains unclear. Molecular profiling based on the next-generation sequencing (NGS) method, which allows multigenomic research of ovarian tumors, is not widely used among clinicians in routine clinical practice in Ukraine.
The aim of this study was to evaluate the informativeness of molecular genetic testing using a panel that detects damage to genes of signaling pathways and the homologous recombination system (HRR) for the final diagnosis and determination of the treatment plan for patients with ovarian cancer (OC).
Methods and materials. 30 patients with OC at stages III-IV undergoing inpatient treatment at the Lviv Regional Oncology Treatment and Diagnostic Center (LROTDC) during 2019–2023 were examined. The presence of germinal and somatic mutations in 32 genes was investigated using the NGS method, including genes of the HRR system, genes of signaling pathways (BRAF, ERBB2, KRAS, NRAS, РІКЗСА) and the ТР53 gene.
Results. Mutational changes were identified in the tumors of 23 (76.7%) examined patients and in the peripheral blood of 2 (6.7%) patients. Out of 25 cases, DNA repair deficiency by homologous recombination (HRD status) was detected in 14 samples (56%), distributed by tumor morphotype as follows: high-grade serous carcinoma (HGSC) – 9 samples (64.3%), endometrial cancer – 3 samples ( 21.4%) and clear cell carcinoma – 2 samples (14.3%). TP53 mutation was detected in 10 cases (40%), of which seven patients had HGSC (70%). The presence of a KRAS mutation was found in 3 patients (12%) with the morphology of endometrial cancer (2 cases, 66.7%) and HGSC (1 case, 33.3%). A relatively rare AR mutation was also detected in one patient (4%).
HRD status correlated with high sensitivity to platinum-based chemotherapy (85.7% – chemosensitive, 14.3% – chemoresistant). Conversely, the presence of KRAS mutation made it possible to attribute the patient to another morphogenetic type, namely, low-grade serous ovarian cancer, and to apply adjuvant hormone therapy.
Conclusions: Molecular genetic profiling allows for clarifying the morphogenetic type of ovarian cancer and adjusting the patient’s treatment strategy, considering that it is advisable to carry it out at the stages of primary diagnosis of common OC forms.