Human epidermal growth factor receptor-2 expression and subsequent dynamic changes in patients with ovarian cancer.

Human epidermal growth factor receptor-2 (HER2)-targeting drugs are increasingly being incorporated into therapeutic paradigms for non-breast cancers, yet studies on HER2 expression in ovarian cancer (OC) are inadequate. Here, we studied the HER2 status and dynamic changes in OC by reviewing the records of patients who underwent HER2 testing at a single institution. Clinical parameters, including histology, BRCA status, and immunohistochemistry (IHC), were evaluated alongside HER2 expression, timing, and anatomical location. Among 200 patients, 28% and 6% exhibited expression scores of 2+ and 3+, respectively. HER2 3+ scores were observed in 23%, 11%, 9%, and 5% of mucinous, endometrioid, clear cell, and high-grade serous tumors, respectively, and were exclusively identified in BRCA-wildtype, mismatch repair-proficient, or PD-L1-low-expressing tumors. The TP53 mutation rate was low, whereas ARID1A, KRAS, and PIK3CA mutations were relatively more prevalent with HER2 scores of 2+ or 3+ than with 0 or 1+. Four of the five tumors with an HER2 3+ score exhibited ERBB2 amplification. Among 19 patients who underwent multiple time-lagged biopsies, 11 showed increased HER2 expression in subsequent biopsies. Patients with HER2-overexpressing OC exhibited distinct histological, IHC, and genomic profiles. HER2-targeting agents are potential options for BRCA-wildtype patients, particularly as later lines of treatment.

Application of precision medicine based on next-generation sequencing and immunohistochemistry in ovarian cancer: a real-world experience.

OBJECTIVE: To evaluate the landscape of gene alterations and immunohistochemistry (IHC) profiles of patients with ovarian cancer for targeted therapy and investigate the real-world experience of applying precision medicine. METHODS: Patients diagnosed with ovarian cancer between January 2015 and May 2021 at Severance Hospital and who underwent tumor next-generation sequencing (NGS) were reviewed. Data on germline mutation, IHC markers for mismatch repair deficiency (MMRd), programmed death ligand 1 (PD-L1) expression, and human epidermal growth factor receptor 2 (HER2) expression were acquired. The use of matched therapy and its clinical outcomes were evaluated. RESULTS: Of the 512 patients who underwent tumor NGS, 403 underwent panel-based germline testing. In patients who underwent both tests, tumor NGS identified 39 patients (9.7%) with BRCA mutations and 16 patients (4.0%) with other homologous recombination repair (HRR)-associated gene mutations, which were not found in germline testing. The most common single nucleotide variants were TP53 (82.2%), ARID1A (10.4%), PIK3CA (9.7%), and KRAS (8.4%). Copy number aberrations were found in 122 patients. MMRd was found in 3.2% of patients, high PD-L1 expression in 10.1%, and HER2 overexpression in 6.5%. Subsequently, 75 patients (14.6%) received a poly (ADP-ribose) polymerase inhibitor based on BRCA mutation and 11 patients (2.1%) based on other HRR-associated gene mutations. Six patients (1.2%) with MMRd underwent immunotherapy. Twenty-eight patients (5.5%) received other matched therapies targeting HER2, fibroblast growth factor receptor, folate receptor alpha, RAS, and PIK3CA. CONCLUSION: A comprehensive review of germline mutation, IHC, and tumor NGS helped identify candidates for precision therapy in patients with ovarian cancer, a proportion of whom received matched therapy.

Risk of obstetric and neonatal morbidity in gestational diabetes in a single institution: A retrospective, observational study.

Gestational diabetes mellitus (GDM) is defined as a carbohydrate intolerance with onset or first recognition occurring during pregnancy and GDM could be risk factor for various maternal fetal complications. This study aimed to investigate risks of maternal and neonatal outcomes according to GDM and normal glucose tolerance. This retrospective, observational study included singleton pregnant women who had received a 50-g oral glucose challenge test in 2nd trimester of gestation and gave birth at National Health Insurance Service Ilsan Hospital. Maternal and neonatal complications were compared between GDM and non-GDM groups. Among the 682 women, 56 were diagnosed with GDM and 626 were non-GDM group. Maternal age was older and prepregnant body mass index was higher in GDM. The rate of cesarean delivery, preeclampsia, and transfusion was similar; however, the incidence of preterm birth was higher in GDM. Multivariate analysis, however, showed that GDM was independent risk factor only for preterm birth in <37 weeks (adjusted odds ratio, 2.25; 95% confidence interval, 1.16-4.36). Regarding neonatal morbidities, APGAR score <7 at 5 minutes and the rate of macrosomia were similar; however, the rates of neonatal intensive care unit (NICU) admission, large for gestational age (LGA), and intubation were higher in GDM. Multivariate analysis, however, showed that GDM was not independent risk factor for LGA, NICU admission, and intubation rate. Compared with the non-GDM group, GDM was associated with an increased likelihood of preterm birth <37 weeks, however, did not increase cesarean delivery, postpartum hemorrhage, LGA, and NICU admission rate. This study showed that the majority of women with GDM delivered with similar maternal and neonatal outcomes in non-GDM women.