Comparison of Claudin 18.2 expression in primary tumors and lymph node metastases in Japanese patients with gastric adenocarcinoma.
Claudin
biomarkers
gastric cancer
immunohistochemistry
prevalence
Journal
Japanese journal of clinical oncology
ISSN: 1465-3621
Titre abrégé: Jpn J Clin Oncol
Pays: England
ID NLM: 0313225
Informations de publication
Date de publication:
01 Sep 2019
01 Sep 2019
Historique:
received:
17
09
2018
revised:
17
01
2019
accepted:
04
05
2019
pubmed:
16
5
2019
medline:
21
12
2019
entrez:
16
5
2019
Statut:
ppublish
Résumé
The monoclonal antibody zolbetuximab (formerly IMAB362), which is being developed as a potential treatment for gastric cancer (GC), targets Claudin 18.2 (CLDN18.2), a GC biomarker. This study aimed to determine the prevalence of CLDN18.2 in primary tumors and lymph node (LN) metastases of Japanese patients with GC. CLDN18.2 expression was investigated in tissue samples from patients with gastric adenocarcinoma archived at Kurume University Medical Center, Japan, between 2000 and 2012. Expression of CLDN18.2 in tumor samples was evaluated by immunohistochemistry using the same detection antibody (43-14A) and assay used in the FAST clinical trial (NCT01630083), a phase 2 randomized trial that compared the safety and antitumor activity of the zolbetuximab-chemotherapy combination with chemotherapy alone. Samples showing any specific staining with ≥1+ intensity were defined as CLDN18.2-positive. Of 263 samples analyzed (134 primary gastric tumors and corresponding LN metastases; 128 primary tumors only; one LN metastases only), CLDN18.2 was detected in 87% (n = 228/262) of all primary tumors and 80% (n = 108/135) of LN metastases. Moderate-to-strong CLDN18.2 expression (≥2+ membrane staining intensity in ≥40% of tumor cells [FAST eligibility criterion]) was observed in 52% (n = 135/262) of primary tumors and 45% (n = 61/135) of (LN) metastases. CLDN18.2 expression was significantly higher in GCs of the diffuse histological subtype per Lauren classification and in high grade (G3) tumors. The high prevalence of CLDN18.2 among Japanese patients with GC supports the therapeutic assessment of zolbetuximab in this population.
Sections du résumé
BACKGROUND
BACKGROUND
The monoclonal antibody zolbetuximab (formerly IMAB362), which is being developed as a potential treatment for gastric cancer (GC), targets Claudin 18.2 (CLDN18.2), a GC biomarker. This study aimed to determine the prevalence of CLDN18.2 in primary tumors and lymph node (LN) metastases of Japanese patients with GC.
METHODS
METHODS
CLDN18.2 expression was investigated in tissue samples from patients with gastric adenocarcinoma archived at Kurume University Medical Center, Japan, between 2000 and 2012. Expression of CLDN18.2 in tumor samples was evaluated by immunohistochemistry using the same detection antibody (43-14A) and assay used in the FAST clinical trial (NCT01630083), a phase 2 randomized trial that compared the safety and antitumor activity of the zolbetuximab-chemotherapy combination with chemotherapy alone. Samples showing any specific staining with ≥1+ intensity were defined as CLDN18.2-positive.
RESULTS
RESULTS
Of 263 samples analyzed (134 primary gastric tumors and corresponding LN metastases; 128 primary tumors only; one LN metastases only), CLDN18.2 was detected in 87% (n = 228/262) of all primary tumors and 80% (n = 108/135) of LN metastases. Moderate-to-strong CLDN18.2 expression (≥2+ membrane staining intensity in ≥40% of tumor cells [FAST eligibility criterion]) was observed in 52% (n = 135/262) of primary tumors and 45% (n = 61/135) of (LN) metastases. CLDN18.2 expression was significantly higher in GCs of the diffuse histological subtype per Lauren classification and in high grade (G3) tumors.
CONCLUSIONS
CONCLUSIONS
The high prevalence of CLDN18.2 among Japanese patients with GC supports the therapeutic assessment of zolbetuximab in this population.
Identifiants
pubmed: 31087075
pii: 5489144
doi: 10.1093/jjco/hyz068
pmc: PMC6792344
doi:
Substances chimiques
Antibodies, Monoclonal
0
CLDN18 protein, human
0
Claudins
0
zolbetuximab
TF5MPQ8WGY
Types de publication
Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
870-876Informations de copyright
© The Author(s) 2019. Published by Oxford University Press.
Références
World J Gastroenterol. 2008 Feb 28;14(8):1149-55
pubmed: 18300338
Am J Surg Pathol. 2008 Feb;32(2):188-96
pubmed: 18223320
Oncotarget. 2017 Jan 26;8(34):57654-57669
pubmed: 28915702
Cancer Sci. 2007 Jul;98(7):1014-9
pubmed: 17459057
Int J Cancer. 2014 Feb 1;134(3):731-9
pubmed: 23900716
Gastric Cancer. 2011 Jun;14(2):101-12
pubmed: 21573743
Nat Med. 2015 May;21(5):449-56
pubmed: 25894828
Int J Cancer. 2015 Mar 1;136(5):E359-86
pubmed: 25220842
Nat Clin Pract Oncol. 2008 Oct;5(10):588-99
pubmed: 18695711
Virchows Arch. 2011 Jul;459(1):73-80
pubmed: 21607649
J Histochem Cytochem. 2011 Oct;59(10):942-52
pubmed: 21832145
Hum Pathol. 2015 May;46(5):665-72
pubmed: 25800719
Ethn Dis. 2008 Spring;18(2 Suppl 2):S2-70-4
pubmed: 18646324
World J Gastroenterol. 2014 Apr 28;20(16):4483-90
pubmed: 24782601
Eur J Cancer. 2014 May;50(7):1330-44
pubmed: 24650579
Ann Oncol. 2005 Feb;16(2):273-8
pubmed: 15668283
Int J Cancer. 2014 Nov 1;135(9):2206-14
pubmed: 24710653
BMC Gastroenterol. 2015 Feb 05;15:7
pubmed: 25649416
PLoS One. 2013 Sep 20;8(9):e74757
pubmed: 24073219
Clin Cancer Res. 2008 Dec 1;14(23):7624-34
pubmed: 19047087
Am J Surg Pathol. 2008 Aug;32(8):1182-9
pubmed: 18580680
J Cancer. 2012;3:137-44
pubmed: 22481979
J Clin Gastroenterol. 2013 Apr;47(4):322-7
pubmed: 22914345
Gut. 2015 Nov;64(11):1721-31
pubmed: 25385008
J Natl Compr Canc Netw. 2016 Oct;14(10):1313-1320
pubmed: 27697983
Virchows Arch. 2015 Mar;466(3):265-77
pubmed: 25503275
World J Gastroenterol. 2015 Jul 14;21(26):7954-69
pubmed: 26185368
World J Gastroenterol. 2006 Jan 21;12(3):354-62
pubmed: 16489633
Int J Surg. 2014;12(2):156-62
pubmed: 24333468
Eur Surg. 2016;48(5):278-284
pubmed: 27795701
Oncol Rep. 2011 Apr;25(4):971-8
pubmed: 21206985
Lancet. 2016 Nov 26;388(10060):2654-2664
pubmed: 27156933
Expert Rev Clin Pharmacol. 2017 Mar;10(3):263-271
pubmed: 28094573
J Pathol. 2006 Apr;208(5):633-42
pubmed: 16435283