bims-ovdlit 2025-08-10 papers

Int J Gynecol Pathol. 2025 Jul 29.

From Serous Tubal Intraepithelial Carcinoma to Neuroendocrine Carcinoma: Molecular Dissection of a Rare Fallopian Tube Carcinoma.

Jesús Machuca-Aguado, Carmen Alfonso-Rosa, Antonio García-Escudero, Francisco Javier Rubio-Garrido, Inmaculada Trigo, Tatiana Cano-Barbadillo, W Glenn McCluggage.

Primary neuroendocrine carcinoma (NEC) of the fallopian tube is exceptionally rare, with only a small number of cases reported. We report an unusual case in a 77-yr-old woman where a fallopian tube was involved by serous tubal intraepithelial carcinoma (STIC), a small component of high-grade serous carcinoma (HGSC), and a predominant component of small cell neuroendocrine carcinoma (SCNEC). Molecular analysis of microdissected different elements supported a clonal origin, with both tumor components (STIC/HGSC and SCNEC) displaying homologous recombination deficiency and a shared TP53 mutation, while the neuroendocrine component uniquely exhibited 4q deletion and additional DNA repair gene mutations in PALB2 and CHEK2.

Keywords: Fallopian tube; High-grade serous carcinoma; Neuroendocrine carcinoma; STIC; clonal evolution

DOI: https://doi.org/10.1097/PGP.0000000000001127

Nat Genet. 2025 Aug 08.

Whole-genome doubling in ovarian cancer.

Safia Danovi.

DOI: https://doi.org/10.1038/s41588-025-02310-2

Obstet Gynecol Sci. 2025 Aug 05.

A knowledge, attitudes, and practices (KAP) study on BRCA mutations among family members of women diagnosed with epithelial ovarian or fallopian tube cancer.

Sopita Prasertpakdi, Prapaporn Suprasert.

Objective: Breast cancer susceptibility gene (BRCA) gene mutations increase the risk of epithelial ovarian and fallopian tube cancers. Genetic counseling and screening play a crucial role in identifying individuals at risk. Assessing knowledge, attitudes, and practices (KAP) related to BRCA mutations among family members of affected individuals can assist in early detection and preventive strategies. This study aims to evaluate KAP among family members of patients with these cancers to identify gaps and improve awareness.
Methods: A cross-sectional survey was conducted between March and November 2024, involving 215 participants with a family history of epithelial ovarian or fallopian tube cancer. Data were collected through structured interviews.
Results: The mean age of participants was 47.3 years; 42.8% were single, and 44.2% were nulliparous. Most participants (65.6%) had one affected relative, with 86.5% being first-degree relatives. Only 16.3% had heard of BRCA mutations, and 18.2% were aware of their association with ovarian cancer. The most commonly recognized ovarian cancer symptom was abdominal swelling. The highest mean KAP score was associated with the belief that regular pelvic examinations should be performed. Multivariate analysis identified independent factors influencing the desire for BRCA screening, including an attitude score of ≥25 (adjusted odds ratio [AOR], 12.638; P<0.001), follow-up duration of >5 years (AOR, 2.504; P=0.016), and ongoing or ineffective treatment (AOR, 4.303; P<0.001).
Conclusion: Substantial gaps in KAP regarding BRCA mutations persist among family members of affected individuals. Targeted educational interventions and healthcare initiatives are essential to enhance awareness and support informed decision-making in high-risk populations.

Keywords: BRCA mutation; Fallopian tube cancer; Family member; Ovarian cancer

DOI: https://doi.org/10.5468/ogs.25088

Ann Oncol. 2025 Aug 04. pii: S0923-7534(25)00832-4. [Epub ahead of print]

Reply to Letter to the Editor "Long-term follow-up of PAOLA-1 and the evolving landscape of post-PARP treatment strategies in ovarian cancer" by Arenhardt and Nogueira-Rodrigues.

I Ray-Coquard, C Cropet, P Harter, E Pujade-Lauraine, C Marth, D Pérol.

DOI: https://doi.org/10.1016/j.annonc.2025.06.017

Gynecol Oncol. 2025 Aug 07. pii: S0090-8258(25)00952-7. [Epub ahead of print]201 17-25

Role of platinum-free interval (PFI) and maintenance therapies in recurrent ovarian cancer to explain survival. An analysis from the French real-world ESME Ovarian Database.

OBJECTIVE: Approximately 70 % of patients with epithelial ovarian cancer (EOC) will relapse. Beyond the platinum-free interval (PFI), predictive factors for efficacy of subsequent therapies are poorly understood. We evaluated the impact of the PFI on progression-free survival (PFS), overall survival (OS) and the role of therapies used at relapse.
METHODS: This retrospective study using the French ESME Ovarian Database included patients with first relapse of EOC after front-line platinum-based chemotherapy (PBCT). The impact of prognostic factors on survival was analyzed using multivariate Cox regression, with results expressed as hazard ratios, adjusted for patient and tumor characteristics, including a subgroup analysis of high-grade serous cancer.
RESULTS: 5558 patients, treated between 2010 and 2019 were included (median age 65 IQR 57-71). Median second- and third line PFS and OS were proportionally higher with PFI prolongation. Other factors influencing PFS and OS were BRCA mutation, FIGO stage, chemotherapy and maintenance regimens, and PS. PBCT was more effective than single-agent chemotherapy, even with a PFI < 6 months (PFSn2: adjusted HR = 0.48 95 %IC [0.43;0.53], OSn2: HR = 0.51 95 %IC [0.46;0.57]). Use of PARP inhibitors (PARPi) in second line seems to reduce outcomes in the third line. Findings were consistent in the HGSC subgroup.
CONCLUSION: PFI remains an important prognostic factor but should no longer be the sole consideration for treatment selection at relapse in EOC, particularly in HGSC. The potential impact of prior PARPi maintenance on subsequent PBCT warrants investigation in prospective trials.

Keywords: Epithelial; Ovarian cancer; Platinum-free interval; Relapse; Survival; Targeted therapies

DOI: https://doi.org/10.1016/j.ygyno.2025.08.004

Clin Epigenetics. 2025 Aug 07. 17(1): 140

BRCA1 promoter methylation predicts PARPi response in ovarian cancer: insights from the KOMET study.

Léna Nougarede, Florence Hazane-Puch, Florence de Fraipont, Emmanuelle Jacquet, Marie Bidart.

OBJECTIVES: PARP inhibitors (PARPi) have become the new standard maintenance treatment for patients with advanced homologous recombination deficiency (HRD) ovarian cancer; they are also used upon platinum-sensitive relapse. HRD in ovarian cancer is primarily assessed through BRCA genes mutations and genomic scar scores, which are key biomarkers forecasting PARPi benefit. However, the role of BRCA1 promoter methylation in guiding clinical management is unclear. Evidence is needed to improve patient selection before initiating PARPi and to minimize PARPi-related toxicities. Our study aimed to determine the clinical relevance of BRCA1 promoter methylation for patients with ovarian carcinoma.
METHOD: The KOMET (Ovarian Cancer Methylation) study is a single-center retrospective study involving 88 ovarian cancer patients treated between January 2021 and July 2024. Methylation was assessed using Methylation specific high-resolution melting (MS-HRM). Outcomes were measured based on progression-free survival (PFS) from diagnosis and from the initiation of PARPi treatment, as well as overall survival (OS).
RESULTS: A methylated BRCA1 promoter was detected in 17 out of 88 (19%) tumor tissues. Statistically, PFS from PARPi initiation was significantly different between the BRCA1 methylated promoter (BRCA1mp) group and the BRCA1 unmethylated promoter and HRD negative (BRCA1up HRD-) group (p value = 0.0003 log rank test; Hazard Ratio (HR), 95% CI 0.04-0.40). OS was also significantly different between these groups (p value = 0.047 log rank test; HR = 0.30, 95% CI 0.10-0.84), as was PFS from diagnosis (p value = 0.02 log rank test; HR = 0.43, 95% CI 0.21-0.89).
CONCLUSION: BRCA1 promoter methylation in ovarian cancer is associated with a better response to PARPi and platinum salt chemotherapy than tumors without promoter methylation or classical homologous recombination deficiency. Patients with unmethylated BRCA1 promoters and HRD-negative tumors appeared to have a poorer prognosis in terms of PFS from diagnosis. BRCA1 methylation should be considered as a theragnostic biomarker for initiation of PARPi.

DOI: https://doi.org/10.1186/s13148-025-01917-w

J Pathol Clin Res. 2025 Sep;11(5): e70040

Synchronous endometrial/cervical and ovarian/fallopian tube carcinoma: a genome-wide mutation analysis.

Lihong Li, Mengfei Yao, Luyuan Li, Susheng Shi, Yan Song.

In this study, we explored the genomic underpinnings of synchronous endometrial and ovarian/fallopian tube carcinoma (SEOC) and synchronous cervical and ovarian/fallopian tube carcinoma (SCOC), focusing on their clonal relationships to discern whether these malignancies represent dual primary tumors (DPTs) or have metastatic origins. We established a cohort comprising 54 SEOC patients and 7 SCOC patients. After selection, 17 patients (12 SEOC and 5 SCOC) underwent comprehensive analysis via whole-exome sequencing. The study encompassed a diverse array of histological subtypes, including high-grade serous carcinoma (HGSC) or uterine serous carcinoma (USC), endometrioid carcinoma exhibiting papillary/mucinous features, dedifferentiated carcinoma (DC), clear cell carcinoma (CCC), HPV-associated cervical squamous cell carcinoma, and HPV-independent cervical adenocarcinoma. Analysis revealed that 58.3% (7 of 12) of SEOC cases and all SCOC cases demonstrated shared mutations. This suggests a clonal relationship and supports a metastatic origin for these tumors. Notably, metastatic SEOC instances included co-occurrences of USC and HGSC in both the endometrium and the ovaries/fallopian tubes, endometrial and ovarian CCC, concurrent endometrioid endometrial carcinoma (EEC) and endometrioid ovarian carcinoma (EOC) with mucinous metaplasia, as well as cases of endometrial DC with ovarian CCC, and both EEC and ovarian DC. Among the SEOC cases classified as metastatic, patients with high-grade tumors and advanced ovarian stage succumbed to their disease, whereas the remainder survived without relapse. In the SCOC cohort, one patient died from the disease. The favorable survival outcomes across varied histotypes suggest that a stage upgrade may not be warranted. Given the favorable clinical outcomes observed, the term 'trans-tubal spread' may be more appropriate than 'metastasis' in this context to prevent potential overtreatment. Directionality analysis revealed a bidirectional pattern of trans-tubal spread between the uterus/cervix and ovary/fallopian tubes. The presence of dedifferentiated carcinoma confirms the manifestation of dedifferentiation during spread. These findings lend support to the trans-tubal implantation hypothesis and contribute novel insights into the molecular mechanisms underlying tumor dissemination in SEOC and SCOC.

Keywords: genome‐wide; synchronous endometrial/cervical and ovarian/fallopian tube carcinoma; trans‐tubal spread; whole‐exome sequencing

DOI: https://doi.org/10.1002/2056-4538.70040

Mayo Clin Proc. 2025 Aug;pii: S0025-6196(25)00220-4. [Epub ahead of print]100(8): 1450-1452

Rare Causes of Lynch Syndrome: EPCAM Deletion and MSH2 Inversion.

Wei Shen, Lori A Erickson, Sounak Gupta.

DOI: https://doi.org/10.1016/j.mayocp.2025.04.014

Nature. 2025 Aug 07.

These genes can have the opposite effects depending on which parent they came from.

Rachel Fieldhouse.

Keywords: Epigenetics; Genetics; Genomics

DOI: https://doi.org/10.1038/d41586-025-02499-6

Ann Hum Genet. 2025 Aug 05.

The Centenary Special Issue of the Annals of Human Genetics.

John Armour, Rosemary Ekong.

DOI: https://doi.org/10.1111/ahg.70018