Luca Bocciolone

Genomic instability analysis in DNA from Papanicolaou test provides proof-of-principle early diagnosis of high-grade serous ovarian cancer

Late diagnosis and the lack of screening methods for early detection define high-grade serous ovarian cancer (HGSOC) as the gynecological malignancy with the highest mortality rate. In the work presented here, we investigated a retrospective and multicentric cohort of 250 archival Papanicolaou (Pap) test smears collected during routine gynecological screening. Samples were taken at different time points (from 1 month to 13.5 years before diagnosis) from 113 presymptomatic women who were subsequently diagnosed with HGSOC (pre-HGSOC) and from 77 healthy women. Genome instability was detected through low-pass whole-genome sequencing of DNA derived from Pap test samples in terms of copy number profile abnormality (CPA). CPA values of DNA extracted from Pap test samples from pre-HGSOC women were substantially higher than those in samples from healthy women. Consistently with the longitudinal analysis of clonal pathogenic TP53 mutations, this assay could detect HGSOC presence up to 9 years before diagnosis. This finding confirms the continual shedding of tumor cells from fimbriae toward the endocervical canal, suggesting a new path for the early diagnosis of HGSOC. We integrated the CPA score into the EVA (early ovarian cancer) test, the sensitivity of which was 75% (95% CI, 64.97 to 85.79), the specificity 96% (95% CI, 88.35 to 100.00), and the accuracy 81%. This proof-of-principle study indicates that the early diagnosis of HGSOC is feasible through the analysis of genomic alterations in DNA from endocervical smears.

Endometrioid borderline ovarian tumour: A multicentre analysis from the MITO-14 study

The Endometrioid Borderline ovarian tumor (EBOT) is the third most common histological subtype of borderline ovarian tumors. Due to the low incidence of disease, literature is scanty about the prognosis and management of this entity. The aim of this study is to evaluate clinical, surgical characteristics and risk of recurrence in EBOT patients with the experience of the MITO group (Multicenter Italian Trials in Ovarian Cancer). Clinicopathological data from patients with EBOT were retrospectively collected. Descriptive statistics were used to characterize the patient population. Clinicopathological features and treatment variables were evaluated for association with relapse. Fifty-six patients were recruited for this study. Median age of the patient at diagnosis was 49 years (range 34-84). Nineteen women (34 %) had a previous history of endometriosis. Forty-nine (87 %) were with unilateral tumors. Radical surgery was performed for 36 patients and FSS for 20 patients (14 USO, 5 Cystectomy, 1 both procedures). Three patients (6,5 %) had concomitant endometrial cancer (EC) and 4 (8,5 %) had atypical endometrial hyperplasia. Median time to follow up was 89 months (range 3-202). No disease-specific death was observed. During follow up time, 4 patients developed recurrent disease. EBOT is characterized by a good prognosis. Most EBOT tumors are stage I and unilateral. FSS is feasible if performed by experienced surgeons. However, uterine curettage should be done in case of uterine preservation.