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J Ovarian Res. 2016 Aug 26;9(1):52. doi: 10.1186/s13048-016-0259-2.

Genomic alterations in neuroendocrine cancers of the ovary.

Author information

1
The West Cancer Center, 1588 Union Ave., Memphis, TN, 38104, USA.
2
Department of Hematology & Oncology, The University of Tennessee Health Science Center, 956 Court Ave., Suite H310A, Memphis, TN, 38163, USA.
3
Department of Internal Medicine, The University of Tennessee Health Science Center, 956 Court Ave., Suite H314, Memphis, TN, 38163, USA. pprouet@uthsc.edu.
4
Department of Internal Medicine, The University of Tennessee Health Science Center, 956 Court Ave., Suite H314, Memphis, TN, 38163, USA.
5
Caris Life Sciences, 4750 S. 44th Place, Phoenix, AZ, 85040, USA.

Abstract

BACKGROUND:

As we have previously reported, small cell carcinoma of the ovary (SCCO) is a rare, aggressive form of ovarian cancer associated with poor outcomes. In an effort to identify new treatment options, we utilized comprehensive genomic profiling to assess the potential for novel therapies in SCCO.

METHODS:

Patients with SCCO, SCCO-HT (hypercalcemic type), neuroendocrine tumors of the ovary (NET-O), and small cell carcinoma of the lung (SCLC) profiled by Caris Life Sciences between 2007-2015 were identified. Tumors were assessed with up to 21 IHC stains, in situ hybridization of cMET, EGFR, HER2 and PIK3CA, and next-generation sequencing (NGS) as well as Sanger sequencing of selected genes.

RESULTS:

Forty-six patients with SCCO (10 SCCO, 18 SCCO-HT, 18 NET-O) were identified as well as 58 patients with SCLC for comparison. Patients with SCCO and SCCO-HT were younger (median 42 years [range 12-75] and 26 years [range 8-40], respectively) than patients with NET-O 62 [range 13-76] or SCLC 66 [range 36-86]. SCCO patients were more likely to be metastatic (70 %) than SCCO-HT (50 %) or NET-O (33 %) patients, but at a similar rate to SCLC patients (65 %). PD1 expression varied across tumor type with SCCO (100 %), SCCO-HT (60 %), NET-O (33 %) vs SCLC (42 %). PDL1 expression also varied with SCCO (50 %), SCCO-HT (20 %), NET-O (33 %) and SCLC (0 %). No amplifications were identified in cMET, EGFR, or HER2 and only 1 was found in PIK3CA (NET-O). Actionable mutations were rare with 1 patient with SCCO having a BRCA2 mutation and 1 patient with NET-O having a PIK3CA mutation. No other actionable mutations were identified.

CONCLUSIONS:

No recurrent actionable mutations or rearrangements were identified using this platform in SCCO. IHC patterns may help guide the use of chemotherapy in these rare tumors.

KEYWORDS:

Actionable mutation; Chemotherapy; Genomic profiling; Gynecologic malignancies; Small cell carcinoma of ovary

PMID:
27566252
PMCID:
PMC5002197
DOI:
10.1186/s13048-016-0259-2
[Indexed for MEDLINE]
Free PMC Article

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