Objective: DNA repair pathways are potential targets of molecular therapy in cancer patients. The FANCD2, BRIP1, BRCA1/2, and FANCF genes are involved in homologous recombination DNA repair, which implicates their possible role in cell response to DNA-damaging agents. We evaluated a clinical significance of pre-treatment expression of these genes at mRNA level in 99 primary, advanced-stage ovarian carcinomas from patients, who later received taxane-platinum (TP) or platinum-cyclophosphamide (PC) treatment. Methods: Gene expression was determined with the use of Real-Time PCR. The BRCA2 and BRIP1 gene sequence was investigated with the use of SSCP, dHPLC, and PCR-sequencing. Results: Increased FANCD2 expression occurred to be a negative prognostic factor for all patients (PC+TP:HR 3.85, p = 0.0003 for the risk of recurrence; HR 1.96, p = 0.02 for the risk of death), and this association was even stronger in the TP-treated group (HR 6.7, p = 0.0002 and HR 2.33, p = 0.01, respectively). Elevated BRIP1 expression was the only unfavorable molecular factor in the PC-treated patients (HR 8.37, p = 0.02 for the risk of recurrence). Additionally, an increased FANCD2 and BRCA1/2 expression levels were associated with poor ovarian cancer outcome in either TP53-positive or -negative subgroups of the TP-treated patients, however these groups were small. Sequence analysis identified one protein truncating variant (1/99) in BRCA2 and no mutations (0/56) in BRIP1. Conclusions: Our study shows for the first time that FANCD2 overexpression is a strong negative prognostic factor in ovarian cancer, particularly in patients treated with TP regimen. Moreover, increased mRNA level of the BRIP1 is a negative prognostic factor in the PC-treated patients. Next, changes in the BRCA2 and BRIP1 genes are rare and together with other analyzed FA genes considered as homologous recombination deficiency may not affect the expression level of analyzed genes.

Objectives In young patients with borderline tumors the fertility-sparing treatment is indicated, thus the preoperative investigation is important. The aim of this study was to perform a comparative assessment of sensitivity and specificity of selected ultrasonographic and clinical parameters for the diagnoses of borderline tumors and ovarian cancers. Methods We retrospectively analyzed 57 patients who underwent surgical treatment in the Maria Sklodowska-Curie Memorial Cancer Center from Jan 01, 2008 to Dec 31, 2009. Ovarian cancers were diagnosed in 41 patients, and borderline ovarian tumors in 16 patients. Statistical model was developed to determine independent predictive factors that would be useful in preoperative differentiation between both tumors. The model included the following factors: menopausal status, tumor morphology, wall thickness (including outgrowths), septal thickness, echogenicity, resistive index, serum CA-125 level, and free fluid in the peritoneal cavity. Results Based on the statistical model developed, independent predictive factors in the differentiation between ovarian cancers and borderline tumors included the menopausal status (P = 0.005), tumor echogenicity (P = 0.047) and the presence of free fluid in the Douglas pouch (P = 0.043). With the cutoff value of 13 (with scores below 13 indicating a borderline ovarian tumor, and scores of ≥13 indicating ovarian cancer), sensitivity was 90.2 % and specificity was 87 %. Conclusions Our proposed model of preoperative evaluation has a sensitivity of 90 % in the differentiation between ovarian cancers and borderline tumors. When combined with intraoperative findings, it allows optimal surgical therapeutic decisions to be made in patients with borderline ovarian tumors.

Purpose: To assess the recurrence and birth rates among patients with non-epithelial ovarian cancer. Methods: The study included 146 patients with germ cell (GCT, n = 84) and sex cord-stromal tumors (SCST, n = 62), who underwent fertility-sparing surgery. Adjuvant chemotherapy was administered to 86 (58.9%) patients. Most cases (133 out of 146) were staged FIGO I. Results: The 5- and 10-year disease-free survival rates were 91% and 83%, respectively. The recurrence risk was not associated with tumor histology, stage or age. Twenty-four months after the treatment, the rate of recurrence was higher than the rate of childbearing. The childbearing rates kept rising after the treatment and exceeded the rate of recurrence after 2 years. The cumulative incidence rates of birth 36, 60 and 120 months after treatment were 13.24%, 20.75%, and 42.37%, respectively. Chemotherapy was not related to childbearing. The patients’ age was related to the chance of childbearing. Conclusions: The prognoses of GCT and SCST are similar. Close follow-ups along with contraception should be offered to women during the first two years after treatment due to the increased risk of recurrence. After this period, relapses are rare and women can safely become pregnant.

CRNDE is an oncogene expressed as a long non-coding RNA. However, our team previously reported that the CRNDE gene also encodes a micropeptide, CRNDEP. The amino acid sequence of CRNDEP has recently been revealed by other researchers, too. This study aimed to investigate genetic alterations within the CRNDEP-coding region of the CRNDE gene, methylation profiling of this gene, and CRNDEP expression analysis. All investigations were performed on clinical material from patients with ovarian tumors of diverse aggressiveness. We found that CRNDEP levels were significantly elevated in highly aggressive tumors compared to benign neoplasms. Consistently, a high level of this micropeptide was a negative, independent, prognostic, and predictive factor in high-grade ovarian cancer (hgOvCa) patients. The cancer-promoting role of CRNDE(P), shown in our recent study, was also supported by genetic and epigenetic results obtained herein, revealing no CRNDEP-disrupting mutations in any clinical sample. Moreover, in borderline ovarian tumors (BOTS), but not in ovarian cancers, the presence of a single nucleotide polymorphism in CRNDE, rs115515594, significantly increased the risk of recurrence. Consistently, in BOTS only, the same genetic variant was highly overrepresented compared to healthy individuals. We also discovered that hypomethylation of CRNDE is associated with increased aggressiveness of ovarian tumors. Accordingly, hypomethylation of this gene’s promoter/first exon correlated with hgOvCa resistance to chemotherapy, but only in specimens with accumulation of the TP53 tumor suppressor protein. Taken together, these results contribute to a better understanding of the role of CRNDE(P) in tumorigenesis and potentially may lead to improvements in screening, diagnosis, and treatment of ovarian neoplasms.