Gene-Expression Profiling of Mucinous Ovarian Tumors and Comparison with Upper and Lower Gastrointestinal Tumors Identifies Markers Associated with Adverse Outcomes.
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
15 12 2022
15 12 2022
Historique:
received:
24
05
2022
revised:
22
07
2022
accepted:
05
10
2022
pubmed:
13
10
2022
medline:
17
12
2022
entrez:
12
10
2022
Statut:
ppublish
Résumé
Advanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primary MOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and gene-expression data were analyzed to identify prognostic and diagnostic features. Discovery analyses selected 19 genes with prognostic/diagnostic potential. Validation was performed through the Ovarian Tumor Tissue Analysis consortium and GI cancer biobanks comprising 604 patients with MOC (n = 333), mucinous borderline ovarian tumors (MBOT, n = 151), and upper GI (n = 65) and lower GI tumors (n = 55). Infiltrative pattern of invasion was associated with decreased overall survival (OS) within 2 years from diagnosis, compared with expansile pattern in stage I MOC [hazard ratio (HR), 2.77; 95% confidence interval (CI), 1.04-7.41, P = 0.042]. Increased expression of THBS2 and TAGLN was associated with shorter OS in MOC patients (HR, 1.25; 95% CI, 1.04-1.51, P = 0.016) and (HR, 1.21; 95% CI, 1.01-1.45, P = 0.043), respectively. ERBB2 (HER2) amplification or high mRNA expression was evident in 64 of 243 (26%) of MOCs, but only 8 of 243 (3%) were also infiltrative (4/39, 10%) or stage III/IV (4/31, 13%). An infiltrative growth pattern infers poor prognosis within 2 years from diagnosis and may help select stage I patients for adjuvant therapy. High expression of THBS2 and TAGLN in MOC confers an adverse prognosis and is upregulated in the infiltrative subtype, which warrants further investigation. Anti-HER2 therapy should be investigated in a subset of patients. MOC samples clustered with upper GI, yet markers to differentiate these entities remain elusive, suggesting similar underlying biology and shared treatment strategies.
Identifiants
pubmed: 36222710
pii: 709665
doi: 10.1158/1078-0432.CCR-22-1206
pmc: PMC9751776
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
5383-5395Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA047904
Pays : United States
Informations de copyright
©2022 The Authors; Published by the American Association for Cancer Research.
Références
BMC Cancer. 2016 Feb 04;16:55
pubmed: 26847345
Int J Gynecol Cancer. 2019 May 15;:
pubmed: 31097512
Histopathology. 2020 Jul;77(1):26-34
pubmed: 31782197
Clin Cancer Res. 2020 Oct 15;26(20):5400-5410
pubmed: 32737030
Int J Gynecol Cancer. 2018 Mar;28(3):493-499
pubmed: 29466254
Angiogenesis. 2019 Aug;22(3):397-410
pubmed: 30993566
Gynecol Oncol. 2020 Mar;156(3):552-560
pubmed: 31902686
N Engl J Med. 2022 Jul 7;387(1):9-20
pubmed: 35665782
Gynecol Oncol. 2018 Sep;150(3):527-533
pubmed: 30054102
N Engl J Med. 2020 Jun 18;382(25):2419-2430
pubmed: 32469182
Transl Oncol. 2022 Jan;15(1):101266
pubmed: 34794033
Int J Gynecol Pathol. 2005 Jan;24(1):4-25
pubmed: 15626914
Ann Oncol. 2020 Sep;31(9):1240-1250
pubmed: 32473302
Am J Surg Pathol. 2003 Jul;27(7):985-93
pubmed: 12826891
Int J Gynecol Cancer. 2019 May 2;:
pubmed: 31048403
PLoS One. 2013 Apr 19;8(4):e61565
pubmed: 23620766
J Exp Clin Cancer Res. 2018 Jul 24;37(1):166
pubmed: 30041673
Cancer Lett. 2022 Mar 1;528:59-75
pubmed: 34958892
Mod Pathol. 2019 Dec;32(12):1834-1846
pubmed: 31239549
Anticancer Res. 2001 Jul-Aug;21(4B):2983-7
pubmed: 11712798
Int J Gynecol Pathol. 2010 Mar;29(2):99-107
pubmed: 20173494
Gynecol Oncol Rep. 2019 Mar 27;28:109-115
pubmed: 30997376
Int J Clin Exp Pathol. 2014 Jun 15;7(7):4222-30
pubmed: 25120802
Mod Pathol. 2009 Jun;22(6):786-96
pubmed: 19329940
N Engl J Med. 2011 May 12;364(19):1817-25
pubmed: 21561347
Lancet Oncol. 2011 Oct;12(11):1071-80
pubmed: 21616717
J Clin Pathol. 2007 Jun;60(6):622-6
pubmed: 16822880
Arch Pathol Lab Med. 2021 Jun 1;145(6):687-691
pubmed: 32649220
J Natl Compr Canc Netw. 2021 Feb 02;19(2):191-226
pubmed: 33545690
Am J Surg Pathol. 2000 Nov;24(11):1447-64
pubmed: 11075847
J Natl Cancer Inst. 2019 Jan 1;111(1):60-68
pubmed: 29718305
PLoS One. 2016 Apr 20;11(4):e0153844
pubmed: 27096160
N Engl J Med. 2010 Nov 11;363(20):1938-48
pubmed: 21067385
J Ovarian Res. 2021 Feb 14;14(1):33
pubmed: 33583413
Am J Surg Pathol. 2002 Feb;26(2):139-52
pubmed: 11812936
J Pathol. 2013 Jan;229(1):111-20
pubmed: 22899400
Gynecol Oncol. 2019 Jun;153(3):541-548
pubmed: 31005287
Br J Cancer. 2005 Mar 14;92(5):929-34
pubmed: 15756260
Obstet Gynecol. 2019 Dec;134(6):1253-1259
pubmed: 31764736
N Engl J Med. 2019 Mar 28;380(13):1256-1266
pubmed: 30917260
Sci Rep. 2016 Sep 16;6:33366
pubmed: 27632935
Virchows Arch. 2021 May;478(5):885-891
pubmed: 33009577
Curr Treat Options Oncol. 2021 Nov 13;22(12):114
pubmed: 34773517
Nat Commun. 2019 Sep 2;10(1):3935
pubmed: 31477716
BMC Cell Biol. 2013 Mar 19;14:17
pubmed: 23510049
Cancer Sci. 2013 Apr;104(4):423-30
pubmed: 23331552
Cancer. 2011 Feb 1;117(3):554-62
pubmed: 20862744
Eur J Cancer. 2021 Mar;145:158-167
pubmed: 33485079
Clin Cancer Res. 2020 Oct 15;26(20):5411-5423
pubmed: 32554541