Molecular Profiling Reveals Limited Targetable Biomarkers in Neuroendocrine Carcinoma of the Cervix.
Author | Cimic, Adela |
Author | Vranic, Semir |
Author | Arguello, David |
Author | Contreras, Elma |
Author | Gatalica, Zoran |
Author | Swensen, Jeffrey |
Available date | 2020-11-22T06:49:10Z |
Publication Date | 2020-11-15 |
Publication Name | Applied Immunohistochemistry & Molecular Morphology |
Identifier | http://dx.doi.org/10.1097/PAI.0000000000000884 |
Citation | Cimic, Adela MD*; Vranic, Semir MD, PhD†; Arguello, David PhD‡; Contreras, Elma CT (ASCP)‡; Gatalica, Zoran MD, DSc§; Swensen, Jeffrey PhD‡ Molecular Profiling Reveals Limited Targetable Biomarkers in Neuroendocrine Carcinoma of the Cervix, Applied Immunohistochemistry & Molecular Morphology: November 17, 2020 - Volume Publish Ahead of Print - Issue - doi: 10.1097/PAI.0000000000000884 |
ISSN | 1541-2016 |
Abstract | Neuroendocrine carcinoma of the cervix (NEC) is a rare and highly aggressive cervical malignancy. Given that no targeted therapy has been approved specifically to NEC, we investigated the presence of novel, potentially targetable biomarkers in a large cohort of NEC. Sixty-two NEC were molecularly profiled for biomarkers of targeted therapies including antibody-drug conjugates [delta-like canonical notch ligand 3 (DLL3), a trophoblast cell surface antigen 2 (TROP-2), and folate receptor 1 (FOLR1)], NTRK1-3 gene fusions, and immune checkpoint inhibitors [programmed death-ligand 1 (PD-L1), tumor mutational burden, and microsatellite instability] using immunohistochemistry and DNA/RNA next-generation sequencing assays. A cohort of squamous cell carcinomas of the cervix (n=599) was used for comparison for immune-oncology biomarkers. DLL3 expression was observed in 81% of the cases. DLL3 expression was inversely correlated with commonly observed pathogenic mutations in PIK3CA (17%) (P=0.018) and PTEN (10%) (P=0.006). Other more frequently seen pathogenic mutations (TP53 17%, KRAS 11%, and CTNNB1 5%) were not associated with DLL3 expression. TROP-2 expression was detected in only 1 case and no case expressed FOLR1. Although NTRK protein expression was observed in 21% of the cases, none of these had an NTRK gene fusion. PD-L1 expression (10%) and high tumor mutational burden (3%) were significantly less frequent in NEC compared with the squamous cell carcinoma cohort (79% and 11%, respectively). None of the NEC exhibited high microsatellite instability status. Despite frequent DLL3 expression in NEC, a potential therapeutic benefit of DLL3-targeted drugs remains uncertain given the recent failure of the Rova-T therapeutic trial in small cell lung carcinomas. Small cohorts of NEC enriched in PIK3CA/PTEN/AKT and programmed cell death protein 1/PD-L1 alterations indicate therapeutic roles for their respective inhibitors. |
Language | en |
Publisher | Lippincott, Williams & Wilkins |
Subject | neuroendocrine carcinoma cervix molecular profiling precision medicine |
Type | Article |
ESSN | 1533-4058 |
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