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Histology-specific ADC target landscapes in ovarian cancer and therapy-associated antigen downshift after ADC exposure

2026-07-01T00:00:00Z

Title: Histology-specific ADC target landscapes in ovarian cancer and therapy-associated antigen downshift after ADC exposure Authors: Lee, Yong Jae; Park, Junsik; Kim, Yoo-Na; Kim, Soyeon; Jang, Mi; Kim, Sunghoon; Kim, Eun Kyung; Lee, Jung-Yun Abstract: Objective. Antibody-drug conjugates (ADCs) are transforming epithelial ovarian cancer therapy, yet the temporal stability of target expression and the impact of therapeutic pressure remain poorly understood. We characterized the longitudinal evolution of seven key ADC targets and evaluated antigen modulation following ADC exposure. Methods. We analyzed 216 specimens from patients with epithelial ovarian cancer (120 HGSC; 38 nonHGSC). Immunohistochemistry (IHC) was performed for TROP2, HER2, B7H3, B7H4, CLDN6, and CDH6. Expression (over-expression: >= 2+) was assessed at diagnosis, interval debulking, and relapse. FOLR1 expression was categorized as low or high using PS2+ criteria. Target dynamics were evaluated in a limited cohort with paired pre- and post-ADC treatment biopsy specimens. Results. ADC target landscapes were markedly histotype-specific. In HGSC, TROP2 overexpression was observed in all cases (100%), while FOLR1-high expression was present in 86.4% at diagnosis and remained prevalent at relapse (72.6%). Non-HGSC subtypes showed distinct profiles: TROP2 was universally overexpressed in endometrioid and clear cell tumors (100%), while mucinous tumors exhibited a unique HER2-rich landscape (70%). In paired analyses, exposure to cognate ADCs tended to be associated with a downward shift in target expression-particularly for FOLR1, HER2, and CDH6-suggesting a possible trend toward therapy-associated antigen reduction. Conclusions. ADC target expression varied substantially by ovarian cancer histotype. In paired specimens, cognate ADC exposure was associated with a directional decrease in target expression, suggesting possible therapyassociated antigen modulation. These preliminary findings support longitudinal biomarker reassessment to guide subsequent ADC selection and trial eligibility. (c) 2026 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar tech

A multicenter study of laparoscopic versus laparotomic surgery in the treatment of stage I adult granulosa cell and Sertoli-Leydig cell tumors: (LARGES): Gynecologic Oncology Research Investigators coLLaborAtion study (GORILLA-3005)

2026-07-01T00:00:00Z

Title: A multicenter study of laparoscopic versus laparotomic surgery in the treatment of stage I adult granulosa cell and Sertoli-Leydig cell tumors: (LARGES): Gynecologic Oncology Research Investigators coLLaborAtion study (GORILLA-3005) Authors: Kong, Tae-Wook; Lee, Jimin; Kim, Jeeyeon; Son, Joo-Hyuk; Jang, Eun Bi; Shim, Seung-Hyuk; Kim, Nam Kyeong; Kim, Min Kyung; Suh, Dong Hoon; Hwang, Dong Won; Kim, Hee Seung; Lee, Yoo-Young; Lee, Ji Eun; Nam, Eun Ji; Chang, Suk-Joon Abstract: Objective. This study aimed to compare the oncologic outcomes between minimally invasive surgery (MIS) and laparotomic surgery in stage I adult granulosa cell tumors (aGCTs) and Sertoli-Leydig cell tumors (SLCTs). Methods. A total of 337 patients with aGCTs (n = 288) and SLCTs (n = 49) between February 2001 and April 2022 were included. Clinicopathological features were evaluated to determine their association with recurrence. Disease-free survival (DFS) was estimated using the Kaplan-Meier method. Prognostic factors for DFS were determined using the Cox proportional hazards regression model with backward elimination. Results. The median follow-up time was 53.0 months (range, 6-230 months). Of the 157 patients who underwent laparotomy, 12 (7.6%) experienced disease recurrence (7 peritoneal seedings). Among the 180 patients who underwent laparoscopic surgery, 21 (11.7%) showed disease recurrence (15 peritoneal seedings). The 10-year DFS rates were significantly different between the two groups (74.3% vs. 53.9%, p = 0.040). In multivariate analysis, the risk factors associated with disease recurrence were International Federation of Gynecology and Obstetrics stage IC (odds ratio [OR], 3.058; 95% confidence interval [CI], 1.482-6.312; p = 0.002) and ovarian tumor morcellation (OR, 2.848; 95% CI, 1.432-5.663; p = 0.003). Conclusions. In stage I aGCTs and SLCTs, FIGO stage IC and tumor morcellation were independently associated with worse DFS. Although MIS itself was not independently associated with DFS after adjustment, tumor morcellation occurred more frequently in the MIS group. These findings highlight the importance of careful surgical approach selection and strict adherence to oncologic principles, particularly intact tumor resection and avoidance of tumor morcellation, when considering MIS. (c) 2026 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Uterine Artery Embolization for Pure Adenomyosis: Predictive Factors Affecting Outcomes

2026-06-01T00:00:00Z

Title: Uterine Artery Embolization for Pure Adenomyosis: Predictive Factors Affecting Outcomes Authors: Han, Kichang; Kim, Man-Deuk; Kwon, Joon Ho; Seo, Seok Kyo; Alqarni, Abdullah Ali; Park, Juil; Kim, Gyoung Min; Won, Jong Yun; Cho, Jaesung; Jeong, Seok Min Abstract: Purpose: To identify factors associated with postprocedural necrosis after uterine artery embolization (UAE) for pure adenomyosis. Materials and Methods: This study included patients who underwent UAE for pure symptomatic adenomyosis between January 2011 and May 2025. Adenomyosis characteristics, including T2-weighted signal intensity, adenomyosis morphology (Types I and II), and focal versus diffuse location, were evaluated using preprocedural magnetic resonance (MR) imaging. Contrast-enhanced MR imaging was used to assess adenomyosis necrosis 3 months after UAE. Symptom severity scores (SSSs) and health-related quality of life (HRQOL) were evaluated before and 3 months after the procedure. Univariate and multivariate analyses were performed to identify factors associated with incomplete necrosis of the adenomyotic tissue. Results: Of the 147 patients (mean age, 42.7 years [SD +/- 4.2]) who underwent UAE for adenomyosis, 116 (78.9%) exhibited complete necrosis. In multivariate analysis, Type II adenomyosis (odds ratio [OR], 10.492; 95% CI, 3.492-31.523; P < .001) and heterogeneous T2 signal intensity (OR, 4.003; 95% CI, 1.565-10.242; P = .003) were significant predictive factors for incomplete necrosis. The rates of incomplete necrosis were 13.6% (17/125) for Type I adenomyosis and 63.6% (14/22) for Type II adenomyosis. The postprocedural SSS and HRQOL scores were significantly improved in patients with complete necrosis compared with those with incomplete necrosis. Conclusions: Type II morphology arising from the subserosa and a heterogeneous T2 signal are associated with an increased risk of incomplete necrosis after UAE. Incorporating these features into preprocedural counseling may help improve clinical outcomes.

Microbiome in women with endometriosis and the in vitro effects of Lactobacillus reuteri on human endometrium

2026-06-01T00:00:00Z

Title: Microbiome in women with endometriosis and the in vitro effects of Lactobacillus reuteri on human endometrium Authors: Lee, Jae Hoon; Jung, Gee Soo; Kim, Kyungmin; Park, Hyemin; Park, Yunjeong; Lee, Inha; Lee, Min Jung; Lee, Ji-Ho; Choi, Young Sik; Cho, SiHyun Abstract: Endometriosis (EMS) is a chronic inflammatory disorder affecting similar to 10% of reproductive-age women, with increasing evidence implicating the microbiome in its pathogenesis through immunomodulation and estrogen metabolism. This study investigated microbiome composition in the vagina, endometrium, and peritoneal fluid (PF) of women with and without EMS and further assessed the effects of Lactobacillus reuteri (L. reuteri) on endometrial (EM) cells in vitro. Samples from 41 patients were analyzed using 16S rRNA gene sequencing, targeting the V3-V4 regions. Western blotting, ELISA, and LC-MS/MS were employed to evaluate protein expression and estrogen metabolism during EM-L. reuteri co-culture with or without estradiol-17-glucuronide (E2G). Microbiome analysis revealed no significant differences in alpha or beta diversity between EMS and controls across all compartments. However, LEfSe analysis identified several taxa with differential abundance, with L. reuteri consistently altered in both vagina and EM. Across the menstrual cycle, EM and vaginal microbiomes were stable, whereas PF microbiota showed phase-dependent variation involving 60 genera and 76 species. In vitro, L. reuteri alone did not alter endometriosis-related proteins, but in the presence of E2G, it reduced BAX/Bcl-2 ratios and increased p-NF-kappa B, suggesting anti-apoptotic and pro-inflammatory shifts. Progesterone receptor alpha/beta expression decreased, while estrogen receptor levels remained unchanged. L. reuteri increased beta-glucuronidase activity but did not enhance E2G-to-estradiol conversion. These findings highlight L. reuteri as a potentially important species in EMS, with in vitro evidence suggesting survival-promoting effects under estrogenic conditions. Further research should explore multi-species interactions and hormonal contexts to clarify microbial contributions to EMS pathogenesis. IMPORTANCE Although Lactobacillus reuteri appeared more abundant in the vagina and endometrium of controls, suggesting a protective role, in vitro findings paradoxically indicated anti-apoptotic and pro-inflammatory effects under estrogenic conditions, underscoring the need for further investigation of multi-species microbial interactions and hormonal contexts in endometriosis pathogenesis.