O-309 Safety and fertility potential of residual ovarian cortex surrounding borderline tumors in women of reproductive age
Authors: Cacciottola L , Camboni A , Gatti E , Marbaix E , Vignali M , Donnez J , Dolmans M  M 
Published: July 2024

Abstract

Study question
How do borderline ovarian tumors (BOTs) at different oncological stages affect safety (presence of occult lesions) and quality of the ovarian reserve?

Summary answer
The ovarian follicle pool is decreased in women with BOTS, especially at younger age, and oncological safety is compromised in more advanced oncological stages.

What is known already
The clinical decision-making balancing the type of surgical treatment (radical or fertility-sparing) with the the risk of recurrence is still controversial for women diagnosed with BOTs at different oncological stages. The same is for the use of adjuvant techniques like oocyte or ovarian tissue cryopreservation to optimize the likelihood of fertility recovery. The prevalence of occult lesions in healthy-looking ovarian cortex, which may be managed by surgery or cryopreservation, has not been analyzed in all tumor types. Moreover, the status of the ovarian follicle pool may be affected by tumoral masses, making fertility preservation even more challenging in these patients.

Study design, size, duration
Multicentric retrospective study involving Cliniques Universitaires Saint Luc in Brussels (Belgium) and Macedonio Melloni hospital in Milan (Italy). Forty-two women at reproductive age (15-45 years) diagnosed with borderline ovarian tumors (BOTs), including 24 serous, 14 mucinous and 4 endometrioid BOTs were included.

Participants/materials, setting, methods
Histological samples of ovarian cortex surrounding tumors were analyzed to characterize the follicle pool (follicle density, classification and atresia rates) and results were compared with an aged-matched population of 45 subjects with non-ovarian pathologies. Any occult malignant lesions in healthy-looking cortex were investigated using tumor-specific markers (cytokeratin 7 and mucin 1), while immune system infiltration was quantified by CD3 for tumor-infiltrating lymphocytes (TILs) and CD68 for tumor associated macrophages (TAMs).

Main results and the role of chance
Occult ovarian lesions were observed in 5 out of 39 cases (12.8%). These included one mucinous stage-I BOT (1/13), one serous stage-I BOT (1/13), and 3 advanced-stage serous BOTs (3/11). Three 3 cases were excluded from the analysis because no cortex was available. Notably, follicle density was significantly lower in subjects diagnosed with ovarian tumors than in controls (p &lt; 0.001) at a younger age, while no difference was detected in older patients. Significantly greater follicle atresia was encountered in the ovarian tumor group than in controls (20.1 ± 8.8% vs 9.2 ± 9.4%, p &lt; 0.001) at all ages, but no difference was detected in follicle classification parameters (primordial and growing follicle rates). Mucinous BOTs exhibited lower follicle density than serous BOTs (98.8 ± 152.8 vs 225.8 ± 220.7, p &lt; 0.01), although no age difference was evidenced. Although mucinous BOTS had also significantly bigger volume than serous BOTs, no significant correlation between follicle density and tumoral volume was found. Other factors like tumor microenvironment may play a role in ovarian follicle pool damage. Both TILs and TAMs were found in ovarian tumors irrespective of histotype, but no link was established with the status of the ovarian reserve.

Limitations, reasons for caution
Although this study helped to elucidate the risk profile of different types of epithelial ovarian tumors, observing that late-stage BOTs ran a 27% (3/11) risk of occult ovarian lesions, further research is needed to identify predictive markers.

Wider implications of the findings
Personalized counseling for fertility preservation is required in case of BOTs. Fertility-sparing surgery and adjuvant gamete preservation should be considered, balancing any oncological risks against tumor stage and histotype and fertility potential, especially at a younger age.

Trial registration number
NA