Claudin 18 is not a biomarker for breast mucinous tumor
Related Experiment Video
Updated: Sep 15, 2026
Analysis of Protein-protein Interactions and Co-localization Between Components of Gap, Tight, and Adherens Junctions in Murine Mammary Glands
Published on: May 30, 2017
Shih-En Lin1, Shih-Jheng Liou1, Wan-Ching Chen1
1Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, ROC.
Background:
Breast mucinous cystadenocarcinoma (BMCA) is an exceptionally rare malignancy that may resemble mucinous neoplasms of the pancreas, ovary, lung, and colorectum. Claudin 18 (CLDN18), particularly its gastric-associated isoform CLDN18.2, is an emerging therapeutic target; however, CLDN18 immunoreactivity has not been systematically evaluated in BMCA. We investigated whether CLDN18 could distinguish BMCA from breast mucinous carcinoma (BMC) and selected extramammary mucinous mimics.
Methods:
Immunohistochemical (IHC) analysis for CLDN18, cytokeratin 7 (CK7), and cytokeratin 20 (CK20) was performed on 42 mucinous neoplasms comprising BMCA (n = 3), BMC (n = 9), pulmonary invasive mucinous adenocarcinoma (n = 8), colorectal mucinous adenocarcinoma (n = 10), ovarian mucinous tumors (n = 6), and pancreatic mucinous cystic neoplasms (n = 6). Staining intensity and percentage of positive cells were independently evaluated by two pathologists. Previously published TRPS1, organ-lineage marker, and molecular findings from the same three BMCA cases were incorporated for diagnostic correlation.
Results:
All three BMCA and all nine BMC cases were CK7-positive, CK20-negative, and lacked membranous CLDN18 staining. Mammary lineage and differentiation of the three BMCA cases were supported by previously shown TRPS1 nuclear expression. CLDN18 staining was detected in five of six pancreatic, five of six ovarian, and six of eight pulmonary mucinous tumors, while seven of 10 colorectal cases were negative, two were focally positive, and one was diffusely positive. CLDN18 thus provided information beyond CK7/CK20, particularly in pancreatic, ovarian, and pulmonary mucinous tumors, but not in mammary mucinous tumors including BMCA.
Conclusion:
In this limited cohort of three BMCA, CLDN18 did not distinguish BMCA from BMC. TRPS1 provided positive support for mammary lineage, whereas CLDN18 negativity offered supplementary exclusionary evidence against selected extramammary mucinous tumors. CLDN18 should therefore be interpreted with morphology, clinical findings, CK7/CK20, and established lineage markers. Larger multicenter studies are warranted to validate its adjunctive diagnostic role in mucin-rich breast lesions.
