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AuthorVranic, S
AuthorArguello, D
AuthorContreras, E
AuthorCimic, A
AuthorGatalica, Z
Available date2019-10-06T06:22:22Z
Publication Date2019-10-01
Publication NameAnnals of Oncologyen_US
CitationVranic, S., Arguello, D., Contreras, E., Cimic, A., & Gatalica, Z. (2019). 1057P Molecular profiling reveals novel targetable biomarkers in neuroendocrine carcinoma of the uterine cervix. Annals of Oncology, 30(Supplement_5), mdz250-065.‏
AbstractBackground Neuroendocrine carcinoma of the uterine cervix (NEC) is a rare cervical malignancy, accounting for 0.9% of all cervical carcinomas. Cervical NEC is a high-grade cancer with an aggressive clinical course and poor outcome. Given that no target therapy has been approved yet for NEC, we explored novel targetable biomarkers in a large cohort of NEC of the cervix. Methods Sixty-two NEC of the cervix were profiled for biomarkers of targeted therapy including antibody-drug conjugates (DLL3, TROP-2, and FOLR1), tropomyosin receptor kinases (NTRK1/2/3 gene fusions), and immune checkpoint inhibitors (PD-L1, TMB, and MSI) using immunohistochemistry and DNA/RNA next-generation sequencing assays. Results The study included 36 primary and 26 metastatic cervical NEC. The mean patient’s age was 43.6 years (range, 24-82 years). DLL3 expression was observed in 81% of the cases with 49% of cases expressing diffusely (≥50% of positive cancer cells) DLL3 protein. DLL3 expression was inversely correlated with commonly observed mutations: PIK3CA (7/47) (p = 0.018) and PTEN mutations (5/40) (p = 0.006). Other frequently seen mutations (TP53 17%, KRAS 11% and CTTNB1 5%) were not associated with DLL3 expression. PD-L1 expression, high TMB and MSI-H were seen in single cases. Although NTRK protein expression was observed in 21% of the cases, none of these had confirmatory NTRK gene fusions. TROP-2 and FOLR1 were negative in all tested cases. Conclusions DLL3 protein and PIK3CA/PTEN pathway genes may be potential therapeutic targets for a substantial proportion of the patients NEC of the cervix. Based on I-O biomarkers status, the patients with cervical NEC are less likely to benefit from immune checkpoint inhibitors.
PublisherOxford University Press
Subjectneuroendocrine carcinoma
Subjectmolecular profiling
TitleMolecular profiling reveals novel targetable biomarkers in neuroendocrine carcinoma of the uterine cervix
TypeConference Paper
Volume Number30

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