Mucinous ovarian carcinomas (MCs) typically do not respond to current conventional therapy. We have previously demonstrated amplification of HER2 in 6 of 33 (18.2%) mucinous ovarian carcinomas (MCs) and presented anecdotal evidence of response with HER2-targeted treatment in a small series of women with recurrent HER2-amplified (HER2+) MC. Here, we explore HER2 amplification and KRAS mutation status in an independent cohort of 189 MCs and 199 mucinous borderline ovarian tumours (MBOTs) and their association to clinicopathological features. HER2 status was assessed by immunohistochemistry (IHC), FISH, and CISH, and interpreted per ASCO/CAP guidelines, with intratumoural heterogeneity assessment on full sections, where available. KRAS mutation testing was performed with Sanger sequencing. Stage and grade were associated with recurrence on both univariate and multivariate analysis (p < 0.001). Assessment of HER2 status revealed overexpression/amplification of HER2 in 29/154 (18.8%) MCs and 11/176 (6.2%) MBOTs. There was excellent agreement between IHC, FISH, and CISH assessment of HER2 status (perfect concordance of HER2 0 or 1+ IHC with non-amplified status, and 3+ IHC with amplified status). KRAS mutations were seen in 31/71 (43.6%) MCs and 26/33 (78.8%) MBOTs, and were near mutually exclusive of HER2 amplification. In the 189 MC cases, a total of 54 recurrences and 59 deaths (53 of progressive disease) were observed. Within MCs, either HER2 amplification/overexpression or KRAS mutation was associated with decreased likelihood of disease recurrence (p = 0.019) or death (p = 0.0041) when compared to cases with neither feature. Intratumoural heterogeneity was noted in 26% of HER2-overexpressing cases. These data support the stratification of MCs for the testing of new treatments, with HER2-targeted therapy as a viable option for HER2+ advanced or recurrent disease. Further research is required to delineate the molecular and clinical features of the ∼34% of MC cases with neither HER2 amplification nor KRAS mutations.
OBJECTIVES To identify independent risk factors for cesarean delivery after induction of labor (IOL) and to develop a nomogram for predicting cesarean delivery among nulliparous women undergoing IOL at term. METHODS This is a retrospective cohort study including nulliparous women with singleton, term (≥37 0/7 weeks of gestation), cephalic pregnancies undergoing IOL from July 1, 2006, through May 31, 2012, at a tertiary care academic center. Inductions were identified using ICD-9 codes. Demographic, delivery, and outcome data were abstracted manually from the medical record. Women with a contraindication to vaginal delivery (malpresentation, abnormal placentation, prior myomectomy) were excluded. Independent risk factors for cesarean delivery were identified using logistic regression. RESULTS During the study period, there were 785 nulliparous inductions who met study criteria; 231 (29.4%) underwent cesarean delivery. Independent risk factors associated with an increased risk of cesarean delivery included older maternal age, shorter maternal height, greater body mass index, greater weight gain during pregnancy, older gestational age, hypertension, diabetes mellitus, and initial cervical dilation <3 cm. A nomogram was constructed based on the final model with a bias-corrected c-index of 0.709 (95% CI 0.671–0.750). CONCLUSION We identified independent risk factors which can be utilized to predict cesarean delivery among nulliparous women undergoing IOL at term. If validated in other populations, the nomogram could be useful for individualized counseling of women with a combination of identifiable antepartum risk factors.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.