bims-ovdlit 2025-12-07 papers

J Pathol Inform. 2025 Nov;19 100522

Weakly supervised deep learning-based detection of serous tubal intraepithelial carcinoma in fallopian tubes.

Andrew L Valesano, Stephanie L Skala, Mustafa Yousif.

Serous tubal intraepithelial carcinoma (STIC) is an uncommon, non-invasive carcinoma that occurs more frequently in individuals with germline BRCA mutations and is an established precursor to high-grade serous ovarian carcinoma. STIC can be challenging to detect during pathologist evaluation, as it can manifest as a small focus of atypia in an otherwise benign salpingectomy specimen. There is a clinical need for scalable, weakly supervised computational approaches to aid in the detection of STIC. We developed a deep learning model to identify STIC and serous tubal intraepithelial lesions (STIL) in whole-slide images. We obtained fallopian tube specimens diagnosed as STIC (n = 49), STIL (n = 48), and benign fallopian tube (n = 83) at a single academic medical center. We trained a weakly supervised, attention-based multiple instance learning model and evaluated performance on independent datasets, including an additional unbalanced dataset (n = 40 benign, n = 2 STIL, n = 1 STIC) and cases diagnosed descriptively as benign reactive atypia (n = 53). The model achieved high sensitivity and specificity on the balanced validation cohort, with an area under the receiver operating characteristic curve (AUROC) of 0.96 (95% CI: 0.90-1.00), and demonstrated similarly strong performance on unbalanced validation cohorts (AUROC 0.98). Interpretability analyses indicated that model decisions were based on epithelial atypia. These results support the potential of integrating deep learning screening tools into clinical workflows to augment pathologist efficiency and diagnostic accuracy in fallopian tubes.

Keywords: Computational pathology; Deep learning; Gynecological pathology; Multiple instance learning

DOI: https://doi.org/10.1016/j.jpi.2025.100522

JAMA. 2025 Dec 04.

What Is Ovarian Cancer?

Rebecca Voelker.

DOI: https://doi.org/10.1001/jama.2025.18446

Gynecol Oncol Rep. 2025 Dec;62 101993

MECOM amplified endometrial cancer, a novel subset of copy number high tumors associated with poor prognosis.

Shariska P Harrington, Jacqueline Romani, Aminah Jatoi, S John Weroha, Andrea Mariani, William A Cliby, Jamie N Bakkum-Gamez, Dineo Khabele, Alexandre Gaspar-Maia.

Objective: Copy number high (CNH) endometrial cancer (EC) is an aggressive molecular subgroup characterized by TP53 mutations and relative chemoresistance. CNH EC with cyclin E1 gene (CCNE1) amplification and erythroblastic oncogene B (ERBB2) amplification are associated with poor clinical outcomes. MECOM, a complex locus of MDS1 (myelodysplasia syndrome 1) and EVI1 (ecotropic virus integration site 1), has recently been associated with poor prognosis in ovarian cancer. Our objective was to evaluate clinical outcomes of MECOM, CCNE1 and ERBB2 amplified ECs and to provide a literature review on the role of MECOM in gynecologic cancers.
Methods: Copy number variation and molecular subtype classification were extracted from The Cancer Genome Atlas for 529 ECs. Amplification status was determined for MECOM, CCNE1 and ERBB2. Measured clinical outcomes were overall and progression-free survival, covariates included race, stage at diagnosis, and tumor histology. A comprehensive search of peer-reviewed articles was undertaken to summarize evidence on the role of MECOM in gynecologic cancers.
Results: Of all ECs profiled, MECOM was the most frequently amplified gene. Notably, 35% of CNH ECs were MECOM amplified. In multivariate analysis, MECOM amplification without co-amplification of CCNE1 or ERBB2 was associated with an increased risk of death and recurrence, HR 2.3 [1.17-4.62], p = 0.0163 and HR 2.07 [1.08-3.98], p = 0.0282, respectively. The literature review identified 19 relevant studies with inconsistent evidence on MECOM's role in carcinogenesis.
Conclusions: ECs with MECOM amplification are associated with poor clinical outcomes, even in the absence of CCNE1 or ERBB2 amplification. The current literature is limited, and further studies are warranted to determine the role of MECOM amplification in ECs.

Keywords: Copy number high; Endometrial cancer; MECOM; Poor prognosis

DOI: https://doi.org/10.1016/j.gore.2025.101993

Nat Commun. 2025 Dec 02. 16(1): 10826

ctDNA detectability and representativeness in seven body liquids from patients with metastatic breast cancer.

Liquid biopsies enable non-invasive monitoring and characterization of metastatic cancer, primarily through circulating tumor DNA (ctDNA) in blood. The representativeness of all metastatic sites in these liquid biopsies and the clinical relevance of other body fluids remain uncertain. We performed low-pass whole genome sequencing on 216 liquid and 745 metastatic tissue samples from 20 autopsied female patients with metastatic breast cancer to assess ctDNA detection, fraction, and site representativeness in seven body fluids (blood, ascites, cerebrospinal fluid, pericardial fluid, pleural fluid, saliva, and urine). Complementarily, whole exome sequencing on 86 liquid samples from 11 patients explored mutational information. ctDNA was detected in all fluids, but most frequently in blood, followed by ascites, pleural fluid, and cerebrospinal fluid. Phylogenetic reconstruction indicated that site representativeness varies by fluid type. Mutational and gene-level copy number analyses revealed clinically relevant information unique to non-blood fluids. These findings suggest a multi-fluid approach could enhance metastatic cancer monitoring and characterization.

DOI: https://doi.org/10.1038/s41467-025-65838-1

Cell Death Dis. 2025 Dec 05.

The breakome of BRCA1 and BRCA2 pathway mutation carriers reveals early processes in breast oncogenesis.

Sara Oster Flayshman, Osama Hidmi, Jackelyn A Alva-Ornelas, Jonathan Monin, Mark A LaBarge, Victoria L Seewaldt, Yotam Drier, Rami I Aqeilan.

DNA double-strand breaks (DSBs) can lead to genomic instability in cancer. Cells rely on an efficient DNA damage response (DDR) to maintain their DNA integrity and prevent oncogenic transformation. However, the early events that connect recurrent DNA damage to oncogenesis are not yet fully understood. Here, using next-generation sequencing we comprehensively surveyed genomes to identify DSBs in primary cells of non-malignant carriers of BRCA1 and BRCA2 mutations (BRCAmut), categorized as high-risk patients, to characterize the effects of homologous recombination (HR) loss on cancer initiation. We demonstrate that the landscape of physiological DSBs in BRCAmut mammary epithelial cells differs from that of healthy controls and resemble more the DSB pattern observed in breast cancer cells. Our results reveal that proto-oncogenes and tumor suppressors contain more breaks in BRCAmut samples, and that genes with a high number of DSBs tend to be more highly expressed. These genes containing a high number of DSBs are also often mutated in breast cancer tumors. Finally, genes with high DSBs in mammary epithelial cells from women with BRCAmut exhibit a strong correlation with homologous recombination repair. Together, our findings underscore the impact of BRCA loss on the early stages of carcinogenesis and highlight future possibilities for early cancer detection.When BRCA is intact, genes that are highly broken are properly repaired via HR, preserving DNA integrity. When BRCA is mutant, impairing its function, highly broken transcriptional DSB genes emerge, no longer able to be efficiently repaired via HR, and are found at genes related to cancer signaling. Breakome of enriched breaks at high-risk model resembles breast cancer breakome, and breaks can be found in genes known to be frequently mutated in breast cancer.

DOI: https://doi.org/10.1038/s41419-025-08235-2

Discov Oncol. 2025 Dec 03.

Multiomic analysis of CCNE1 amplification associated molecular and immune features in gynecological cancers.

Linlin Liu, Wenjin Zheng, Liang Wen, Zhe Zhang, Yuanguang Meng.

Keywords: CCNE1; Carcinoma; Cervix; Genomics; Ovary; Uterus

DOI: https://doi.org/10.1007/s12672-025-04032-7