Claudin-6 (CLDN6) expression is abundant in many different cancer entities

Claudin-6 (CLDN6) is a member of the claudin membrane protein family, which are crucial components of tight junctions, regulating paracellular permeability and maintaining cell polarity. CLDN6 is early expressed in embryonic stem cells and in specific fetal tissues such as kidney, lung, pancreas, and stomach, but is not expressed in corresponding adult tissues. While CLDN6 expression is largely lacking on normal tissues, it is highly expressed in several cancers. Therefore, CLDN6 is considered a potential therapeutic target. Studies evaluating CLDN6 as a target for monoclonal antibodies, antibody-drug conjugates, bispecific antibodies, and CAR-T cells are underway. To better comprehend the prevalence of CLDN6 expression in different cancer types, CLDN6 was analyzed by immunohistochemistry (IHC) on tissue microarrays (TMAs) containing 4,464 samples from 101 different tumor types. A total of 39 tumor categories showed CLDN6 expression in at least one case, and 21 tumor categories contained at least one strongly positive case. At least weak CLDN6 positivity was most commonly seen in embryonal carcinoma (100%), seminoma (97.8%), and yolk sac tumor of the testis (97.6%), serous high-grade (76.4%), endometrioid (41.0%) and clear cell carcinoma (31.6%) of the ovary, carcinosarcoma of the ovary (66.7%) and the endometrium (36.0%), basal cell carcinoma of the skin (44.4%), adenocarcinoma of the ampulla Vateri (20%), endometrioid endometrial carcinoma (18.9%), adenocarcinoma of the cervix uteri (17.4%), adenocarcinoma of the esophagus (13.9%), gastric adenocarcinoma, intestinal type (11.6%), mucinous carcinoma of the ovary (9.1%), ductal adenocarcinoma of the pancreas (8.9%), muscle-invasive urothelial carcinoma (6.9%), cholangiocarcinoma (5.9%), squamous cell carcinomas of the esophagus (4.5%), vulva (4.3%), skin (4.1%), larynx (3.1%), penis (2.8%), pharynx (2.3%), anal canal (1.7%), oral cavity (1.2%), and the cervix uteri (1.2%), Brenner tumor of the ovary (3.6%), invasive breast carcinoma of no special type (3.5%), hepatocellular carcinoma (2.0%), gastric adenocarcinoma, diffuse type (1.8%), colorectal adenocarcinoma (1.7%), and diffuse large B cell lymphoma (1.0%). Our tumor cohorts were large enough to compare CLDN6 expression with tumor phenotype in ovarian, endometrial and pancreatic cancer. CLDN6 positivity was associated with advanced pT stage (p<0.0001) and high grade (p=0.0003) in ovarian cancer and with high grade in endometrial carcinoma (p=0.0179) but was unrelated to phenotype in pancreatic ductal adenocarcinoma. It is concluded that CLDN6 is expressed at significant levels in many different tumor types. Once anti-CLDN6 drugs are approved as safe and efficient, patients with many different cancer types may benefit from these new therapies.