title: Coupling CDH17 and CLDN18 markers for comprehensive membrane-targeted detection of human gastric cancer.
abstract: Patients with gastric cancer typically face gastrectomies even when few or no nodal metastases are reported. Current procedures poorly predict lymphatic metastases; thus, evaluation of target molecules expressed on cancer cell membranes is necessary for in vivo detection. However, marker development is limited by the intratumoral heterogeneity of gastric cancer cells. In this study, multiple gene expression arrays of 42 systemic normal tissue samples and 56 gastric cancer samples were used to investigate two adhesion molecules, cadherin 17 (CDH17) and claudin 18 (CLDN18), which are intestinal and gastric markers, respectively. Expression of CDH17 and CLDN18 was partially redundant, but overlapped in 50 of 56 cases (89.3%). Tissue microarrays constructed using primary lesions and nodal metastases of 106 advanced gastric cancers revealed CDH17 and CLDN18 expression in 98 positive cases of 106 (92%). Hierarchical clustering classified gastric cancers into three subgroups, CDH17(++)/CLDN18(+/-), CDH17(++)/CLDN18(++) or CDH17(+)/CLDN18(+), and CDH17(-)/CLDN18(++/+/-). Whole tissue sections displayed strong, homogeneous staining for CDH17 and CLDN18. Together, these results indicate that CDH17 and CLDN18 are useful target molecules; moreover, their coupling can aid in the comprehensive detection and localization of gastric cancer metastases in vivo to overcome challenges associated with intratumoral heterogeneity.
authors: Division of Diagnostic Pathology, The University of Tokyo Hospital, Tokyo, Japan.|Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors: Keisuke
authors: K
authors: Matsusaka
authors: Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors: Tetsuo
authors: T
authors: Ushiku
authors: Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan.|Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.|Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors: Masayuki
authors: M
authors: Urabe
authors: Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors: Masaki
authors: M
authors: Fukuyo
authors: Division of Diagnostic Pathology, The University of Tokyo Hospital, Tokyo, Japan.
authors: Hiroyuki
authors: H
authors: Abe
authors: Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.|Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan.
authors: Shumpei
authors: S
authors: Ishikawa
authors: Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors: Yasuyuki
authors: Y
authors: Seto
authors: Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan.
authors: Hiroyuki
authors: H
authors: Aburatani
authors: Department of Quantitative Biology and Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan.
authors: Takao
authors: T
authors: Hamakubo
authors: Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan.|Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan.
authors: Atsushi
authors: A
authors: Kaneda
authors: Division of Diagnostic Pathology, The University of Tokyo Hospital, Tokyo, Japan.|Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors: Masashi
authors: M
authors: Fukayama
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D015820:Cadherins / Q000032:analysis* / Q000235:genetics; D057167:Claudins / Q000032:analysis* / Q000235:genetics; D016000:Cluster Analysis; D005260:Female; D005743:Gastrectomy; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008197:Lymph Node Excision; D008198:Lymph Nodes / Q000737:chemistry* / Q000473:pathology / Q000601:surgery; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D013274:Stomach Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D013997:Time Factors; D046888:Tissue Array Analysis; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C490584:CDH17 protein, human; C486683:CLDN18 protein, human; D015820:Cadherins; D057167:Claudins
keywords: CDH17; CLDN18; gastric cancer; intratumoral heterogeneity; nodal metastases