Abstract 159P
Background
The claudin18 isoform 2 (CLDN18.2), a member of the tight junction protein family, is a highly selective target for development of novel therapies in various primary malignant tumors. Due to the interference of CLDN18.1, which is highly homologous to CLDN18.2, selection of appropriate antibodies still need to be further identified.
Methods
Expression of CLDN18.2 was evaluated in a total of 66 gastric adenocarcinoma samples by immunohistochemistry(IHC) using the pan-CLDN18 antibodies (clone 43-14A and clone MM02), which recognizes both CLDN18.2 and CLDN18.1, and the CLDN18.2-specific antibody (clone EPR19202-244). The results were further verified by qPCR and CLDN18.1-specific antibody respectively.
Results
The CLDN18.2 expression evaluated by 43-14A and MM02 showed highly consistentat in different eligibility criterions (≥ 2+ membrane staining intensity in ≥ 40% or ≥ 75% of tumor cells) with 95.45% and 90.91% overall percent agreements(OPA) respectively. While EPR19202-244 showed low sensitivity (84.38%) compared with 43-14A, even after readjusting the optimal threshold according to the ROC curve and Youden index. CLDN18, CLDN18.1 and CLDN18.2 mRNAs were further measured via quantative real-time PCR and IHC for CLDN18.1 was applied. It was verified that all those samples determined to be negative for CLDN18.2 by EPR19202-244 but positive for CLDN18 by pan-CLDN18 antibodies should be identified as true positive for CLDN18.2. Table: 159P
Comparison of clone 43-14A, clone MM02, and clone EPR19202-244
43-14A/MM02/EPR19202-244 | |||||||||
+/+/+ | +/+/- | +/-/- | -/+/- | -/-/+ | -/+/+ | -/-/- | Total | ||
Samples | 29 | 7 | 0 | 2 | 2 | 1 | 25 | 66 | |
Samples were verified | 20 | 5 | / | 2 | 1 | 0 | 9 | 37 | |
qPCR | pan-CLDN18 | 19 | 4 | 2 | 0 | / | 1* | ||
CLDN18.2 | 19 | 4 | 2 | 0 | 0 | ||||
CLDN18.1 | 0 | 0 | 0 | 0 | 1* | ||||
IHC | CLDN18.1-specific | 0 | 0 | 0 | 0 | 0 |
Note: ≥2+ intensity in ≥40% tumor cells defined as CLDN18.2-positive for 43-14A and MM02, and ≥2+ ≥25% for EPR19202-24. *:Possibly due to technical differences in qPCR and IHC
Conclusions
Our results clarify the differences between EPR19202-244, 43-14A and MM02, and suggesting a higher sensitivity and specificity of pan-claudin18 antibodies, which should be used for the dectction of CLDN18.2.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
W. Su, H. Lu, Q. Yan, J. Xu, C. Hua, Z. Huang, L. Ruan, C. Zhu: Financial Interests, Personal, Full or part-time Employment: Amoy Diagnostics. All other authors have declared no conflicts of interest.
Resources from the same session
144P - Artificial intelligence supported treatment decisions for precision oncology
Presenter: Damian Rieke
Session: Poster session 01
145P - Identification of biomarkers of survival across multiple cancer types using eXplainable artificial intelligence
Presenter: Francesca Angileri
Session: Poster session 01
147P - Non-small cell lung cancer: Artificial intelligence enables the identification of survival signatures complementary to an Immunologically active gene expression signature involving previous therapies
Presenter: Pierre Saintigny
Session: Poster session 01
149P - Assessing the effect of single dose trastuzumab and pertuzumab (HP) on biological changes and pathological complete response (pCR) in ERBB2+ Breast Cancer: Results from the neoadjuvant BionHER study
Presenter: Nadia Gomez Serra
Session: Poster session 01
150P - Validation of a genomic assay in early-stage HER2+ breast cancer (BC) treated with trastuzumab and pertuzumab (HP): A correlative analysis from PHERGain phase II trial
Presenter: Antonio Llombart Cussac
Session: Poster session 01
152P - Efficacy of olaparib in advanced cancers with germline or somatic tumor mutations in BRCA1, BRCA2, CHEK2 and ATM: A Belgian precision tumor-agnostic phase II study
Presenter: Sofie Joris
Session: Poster session 01
153P - Descriptive analysis of the location of point mutations in BRCA and the risk of breast or ovarian cancer diagnosis
Presenter: Pablo Torres-Mozas
Session: Poster session 01
154P - Highly sensitive serum volatolomic biomarkers for pancreatic cancer diagnosis and prognosis
Presenter: Alfredo Martínez
Session: Poster session 01