Recurrent genetic alterations and biomarker expression in primary and metastatic squamous cell carcinomas of the vulva.
Adult
Aged
Aged, 80 and over
B7-H1 Antigen
/ genetics
Baculoviral IAP Repeat-Containing 3 Protein
/ genetics
Biomarkers, Tumor
/ genetics
Carcinoma, Squamous Cell
/ genetics
Cyclin-Dependent Kinase Inhibitor p16
/ genetics
Female
High-Throughput Nucleotide Sequencing
Humans
Middle Aged
Mutation
Proto-Oncogene Proteins p21(ras)
/ genetics
Receptor, Notch1
/ genetics
Tumor Suppressor Protein p53
/ genetics
Vulvar Neoplasms
/ genetics
Mutations
PD-L1
Squamous cell carcinoma
TP53
Vulva
Journal
Human pathology
ISSN: 1532-8392
Titre abrégé: Hum Pathol
Pays: United States
ID NLM: 9421547
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
18
06
2019
revised:
30
07
2019
accepted:
07
08
2019
pubmed:
23
8
2019
medline:
11
6
2020
entrez:
23
8
2019
Statut:
ppublish
Résumé
Using a comprehensive next-generation sequencing pipeline (143 genes), Oncomine Comprehensive v.2, we analyzed genetic alterations on a set of vulvar squamous cell carcinomas (SCCs) with emphasis on the primary and metastatic samples from the same patient, to identify amenable therapeutic targets. Clinicopathologic features were reported and genomic DNA was extracted from 42 paraffin-embedded tumor tissues of 32 cases. PD-L1 expression was evaluated in 20 tumor tissues (10 cases with paired primary and metastatic tumors). Fifteen (88%) of 17 successfully analyzed HPV-unrelated SCCs harbored TP53 mutations. 2 different TP53 mutations had been detected in the same tumor in 4 of 15 cases. Other recurrent genetic alterations in this group of tumors included CDKN2a mutations (41%), HRAS mutations (12%), NOTCH1 mutations (12%) and BIRC3 (11q22.1-22.2) amplification (12%). Six HPV-related tumors harbored PIK3CA, BAP1, PTEN, KDR, CTNNB1, and BRCA2 mutations, of which, one case also contained TP53 mutation. Six cases showed identical mutations in paired primary site and distant metastatic location and four cases displayed different mutational profiles. PD-L1 expression was seen in 6 of 10 primary tumors and all 6 paired cases showed discordant PD-L1 expression in the primary and metastatic sites. Our results further confirmed the genetic alterations that are amenable to targeted therapy, offering the potential for individualized management strategies for the treatment of these aggressive tumors with different etiology. Discordant PD-L1 expression in the primary and metastatic vulvar SCCs highlights the importance of evaluation of PD-L1 expression in different locations to avoid false negative information provided for immunotherapy.
Identifiants
pubmed: 31437519
pii: S0046-8177(19)30136-4
doi: 10.1016/j.humpath.2019.08.003
pmc: PMC6864277
mid: NIHMS1537753
pii:
doi:
Substances chimiques
B7-H1 Antigen
0
Biomarkers, Tumor
0
CD274 protein, human
0
CDKN2A protein, human
0
Cyclin-Dependent Kinase Inhibitor p16
0
NOTCH1 protein, human
0
Receptor, Notch1
0
TP53 protein, human
0
Tumor Suppressor Protein p53
0
Baculoviral IAP Repeat-Containing 3 Protein
EC 2.3.2.27
HRAS protein, human
EC 3.6.5.2
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
67-80Subventions
Organisme : NCI NIH HHS
ID : P50 CA098252
Pays : United States
Informations de copyright
Copyright © 2019. Published by Elsevier Inc.
Références
Oncogene. 2010 Oct 21;29(42):5700-11
pubmed: 20676140
Gynecol Oncol. 1995 Jun;57(3):327-34
pubmed: 7774836
Gynecol Oncol. 2018 Sep;150(3):552-561
pubmed: 29980281
Am J Clin Pathol. 2019 Jan 7;151(2):217-225
pubmed: 30346474
Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4240-5
pubmed: 10200246
Mod Pathol. 2010 Mar;23(3):404-12
pubmed: 20062014
Clin Cancer Res. 2017 Aug 1;23(15):4501-4510
pubmed: 28377483
Gynecol Oncol. 2019 May;153(2):286-291
pubmed: 30760408
Obstet Gynecol. 1996 Jan;87(1):59-64
pubmed: 8532267
Clin Cancer Res. 2018 Feb 1;24(3):600-607
pubmed: 29113987
Oncoimmunology. 2017 Jul 27;6(11):e1356146
pubmed: 29147606
Cancer Res. 2009 Mar 15;69(6):2559-67
pubmed: 19276372
Virchows Arch. 2012 Aug;461(2):123-8
pubmed: 22733500
Ann N Y Acad Sci. 1999;886:191-4
pubmed: 10667217
Ann Oncol. 2016 Oct;27(10):1953-8
pubmed: 27502709
Cancer. 2013 Nov 1;119(21):3776-83
pubmed: 24037752
Cell Signal. 2014 Jan;26(1):149-61
pubmed: 24140475
Cell. 2011 Mar 4;144(5):646-74
pubmed: 21376230
Gynecol Oncol. 2018 May;149(2):310-317
pubmed: 29555332
Int J Cancer. 2017 Dec 15;141(12):2517-2527
pubmed: 28815579
Int J Gynecol Cancer. 2012 Mar;22(3):503-8
pubmed: 22266935
Oncotarget. 2017 Oct 6;8(54):92890-92903
pubmed: 29190964
Am J Hum Genet. 2015 Apr 2;96(4):597-611
pubmed: 25839328
CA Cancer J Clin. 2019 Jan;69(1):7-34
pubmed: 30620402
J Pathol. 2016 Oct;240(2):224-34
pubmed: 27447534
Urol Oncol. 2019 May;37(5):299.e19-299.e25
pubmed: 30660491
Clin Cancer Res. 2016 Sep 15;22(18):4735-45
pubmed: 27091409
Cancer Sci. 2015 Sep;106(9):1118-29
pubmed: 26081045
Neoplasia. 2005 Jun;7(6):556-62
pubmed: 16036106
Histopathology. 2019 Jan;74(2):256-268
pubmed: 30067880
Cancer Immunol Res. 2015 Oct;3(10):1158-64
pubmed: 26014095
Ann Oncol. 2016 Sep;27(9):1696-705
pubmed: 27329249
Mod Pathol. 2019 Mar;32(3):415-422
pubmed: 30291345
Am J Surg Pathol. 2018 Jun;42(6):750-760
pubmed: 29505425
Nature. 2014 Feb 20;506(7488):371-5
pubmed: 24390348
Am J Surg Pathol. 2016 Apr;40(4):529-36
pubmed: 26645728
Gynecol Oncol. 2017 Aug;146(2):305-313
pubmed: 28536037
Br J Cancer. 2003 Dec 15;89(12):2249-53
pubmed: 14676802
Gynecol Oncol. 2014 Oct;135(1):149-55
pubmed: 25072932
Cell Cycle. 2005 Aug;4(8):1004-6
pubmed: 15970711
Oncogene. 1994 Jun;9(6):1655-9
pubmed: 8183560
Int J Surg Pathol. 2018 Sep 18;:1066896918800779
pubmed: 30227763
JAMA Oncol. 2016 Apr;2(4):518-22
pubmed: 26913631
Proc Natl Acad Sci U S A. 2005 May 10;102(19):6936-41
pubmed: 15860581