Molecular profiling reveals novel targetable biomarkers in neuroendocrine carcinoma of the uterine cervix
Author | Vranic, S |
Author | Arguello, D |
Author | Contreras, E |
Author | Cimic, A |
Author | Gatalica, Z |
Available date | 2019-10-06T06:22:22Z |
Publication Date | 2019-10-01 |
Publication Name | Annals of Oncology |
Identifier | http://dx.doi.org/10.1093/annonc/mdz250.065 |
Citation | Vranic, 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. |
ISSN | 0923-7534 |
Abstract | Background 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. |
Language | en |
Publisher | Oxford University Press |
Subject | cervix neuroendocrine carcinoma molecular profiling |
Type | Conference Paper |
Volume Number | 30 |
ESSN | 1569-8041 |
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