For patients diagnosed with gastric or gastroesophageal junction (G/GEJ) adenocarcinoma:
Testing for CLDN18.2 uses standard IHC staining methods, with interpretation according to membranous stain intensity and percentage of tumor cells stained.1
Testing for CLDN18.2 uses standard IHC staining methods, with interpretation according to membranous stain intensity and percentage of tumor cells stained.1,2
Due to the heterogeneous cellular composition of G/GEJ tumor cells, CLDN18.2 is reported for both membranous staining intensity and percentage of tumor cells stained.1
Data in patients with G/GEJ cancers suggest that staining for CLDN18.2 is consistent between primary and metastatic tumor samples.3
In a study of 408 primary gastric carcinomas, 115 gastroesophageal carcinomas, and 135 matched and synchronous nodal metastases3,*:
For the evaluation of CLDN18, the membrane immunoreaction was assessed using a semi-quantitative pathology H-score, defined as the aggregate of total percentage of tumor cells expressing CLDN18 at each intensity level from 0, +1 (weak intensity), +2 (moderate intensity), or +3 (strong intensity). The H-score was defined as: (Percentage of CLDN18 1+ tumor cells multiplied by intensity of 1) + (Percentage of CLDN18 2+ tumor cells multiplied by intensity of 2) + (Percentage of CLDN18 3+ tumor cells multiplied by intensity of 3). Thus this composite score could range from 0 (a tumor that is completely negative) to a maximum of 300 (a tumor in which all the cells feature a 3+ staining). Scores were categorized in negative/low (0 = 0–50) and positive/high (1 = 51–300). Where present, nuclear and/or cytoplasmic CLDN18 expression was noted but not retained for scoring.3
As is the case with some other biomarkers such as HER2, CLDN18.2 expression may demonstrate variability within a tumor and this should be taken into account when sampling.3,4
In the same study that demonstrated high-level concordance between primary and metastatic samples, intratumoral heterogeneity in terms of CLDN18.2 expression was found in3,*,†:
Intratumoral variability of membranous CLDN18 expression was investigated, considering CLDN18 expression among multiple TMA cores collected from different areas of the same tumor. A tumor was considered as CLDN18 heterogeneous in case of concomitant presence of high-CLDN18 and low- CLDN18 TMA cores.3
CLDN, claudin; CLDN18.2, claudin 18 isoform 2; GC, gastric cancer; GEC, gastroesophageal cancer; G/GEJ, gastric/gastroesophageal junction; HER2, human epidermal growth factor receptor-2; IHC, immunohistochemistry; TMA, tissue microarray.
References: 1. Pellino A, Brignola S, Riello E, et al. Association of CLDN18 protein expression with clinicopathological features and prognosis in advanced gastric and gastroesophageal junction adenocarcinomas. J Pers Med (Epub) 10-26-2021. 2. Ventana CLDN18 (43-14A) assay [package insert]. Mannheim, Germany: Roche Diagnostics GmbH. 3. Coati I, Lotz G, Fanelli GN, et al. Claudin-18 expression in oesophagogastric adenocarcinomas: a tissue microarray study of 523 molecularly profiled cases. Br J Cancer 2019;121(3):257-63. 4. Grillo F, Fassan M, Sarocchi F, Fiocca R, Mastracci L. HER2 heterogeneity in gastric/gastroesophageal cancers: from benchside to practice. World J Gastroenterol 2016;22(26):5879-87.