Claudin 18.2 expression in various tumor types and its role as a potential target in advanced gastric cancer

ABSTRACT:

Background

Alterations in claudin expression can impair tight junction function, influence signaling pathways, and act as a tumor-promoting event in some epithelial cancers. Recently, zolbetuximab, a highly potent and tumor cell-selective therapeutic antibody against claudin 18.2, has been developed and investigated in clinical trials.

Methods

We conducted a prospective study using claudin 18.2 immunohistochemistry in 430 consecutive patients with advanced gastrointestinal, genitourinary, or rare cancers between June 2012 and March 2016.

Results

Claudin 18.2 expression was evaluated in 96.3% of the patients (414/430) using immunohistochemistry. In total, 4.1% (17/414) of the patients were claudin 18.2-positive, including patients with pancreatic (16.7%, 1/6), gastric (14.1%, 12/85), biliary tract (6.3%, 1/16), genitourinary/miscellaneous (2.2%, 1/46), and colorectal (0.9%, 2/203) cancers. Twelve of 17 patients positive for claudin 18.2 had gastric cancers (GCs); this subgroup showed no statistical differences by gender, age, disease extent, primary tumor site, pathologic differentiation, human epidermal growth factor receptor 2, or Epstein-Barr virus status with or without claudin 18.2 expression. However, claudin 18.2 was more frequently positive in intestinal-type compared with diffuse-type as assessed by Lauren classification (P=0.026). There was no significant difference in overall survival (OS) between patients with and without claudin 18.2 expression (P=0.101).

Conclusions

Our results add to the emerging literature about claudin 18.2 expression in various cancer types and support the need for extended clinical exploration of zolbetuximab.

SUBMITTER: Hong J 

PROVIDER: S-EPMC8797704 | biostudies-literature |

REPOSITORIES: biostudies-literature