Molecular profiling in a large cohort of gynecologic neuroendocrine tumors


E.K. Cranea, P. Ramosb, J.H. Farleyc, R.W. Naumannd, D.L. Taita, R.V. Higginsa, J. Browna. Levine


Neuroendocrine tumors (NETs) of the gynecologic tract have historically represented rare, aggressive tumors with a poor prognosis, high rates of recurrence despite multimodal treatment, and limited therapeutic options. The objective of this study was to identify potential therapeutic targets for gynecologic NETs through molecular profiling of a large cohort of patients.


Molecular testing results (including gene mutation, gene fusion, copy number variation [CNV], and immunohistochemistry [IHC]) for patients with gynecologic NETs were retrieved from the Caris Life Sciences database. Proportion of patients with positive test results was calculated.


In the CARIS database we identified 120 patients with gynecologic NETs. Origin of tumor was cervical in 70 patients (54%), uterine in 31 (24%), ovarian/fallopian tube in 21 (16%), vaginal in 6 (5%), and vulvar in 1 (1%). In a DNA 592 gene panel, the following aberrations were observed in mutational analyses: TP53 (43%), ARID1A (37%), PIK3CA (19%), PTEN (18%), RB1 (13%), and CTNNB1 (10%). In IHC, PTEN (83%), and PD1 (50%) had high expression, and mismatch repair proteins were largely expressed (94%). ER and PR staining was generally low (6% and 5%, respectively). CNV was also infrequent, with CCNE1 amplifications being the most common event (8%). Microsatellite instability was rare (8%), and tumor mutational load was low (96%), which was consistent across subsets of NETs analyzed by tumor site. No clinically relevant fusions were identified.


To date, this is the largest cohort of gynecologic NETs that have been molecularly described. Unfortunately, these tumors are molecularly heterogeneous with few actionable alterations

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