Utility of WT-1, p63, MOC31, mesothelin, and cytokeratin (K903 and CK5/6) immunostains in differentiating adenocarcinoma, squamous cell carcinoma, and malignant mesothelioma in effusions

Diagnostic Cytopathology. 2007 Dec 6;36(1):20-25 [Epub ahead of print] [Link]

Pu RT, Pang Y, Michael CW.

Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan.


To distinguish carcinoma, either adenocarcinoma (ADC) or squamous cell carcinoma (SCC), and malignant mesothelioma (MM) in effusion can be a diagnostic challenge based on morphology alone. This study evaluates the utility of WT-1, p63, MOC31, mesothelin, and cytokeratin (K903 and CK5/6) immunostains in effusions when ADC and SCC of the lung are in the differential diagnosis with MM. A cohort of 43 effusions consisting of lung ADC (N = 10), SCC (N = 15), and MM (N = 18, mostly (16) pleural based), was subjected to immunostains using the above mentioned antibodies. WT-1 was positive in 100% MM, 0% ADC, and 0% SCC cases while p63 was positive in 0% MM, 30% ADC, and 80% SCC cases. Stain for MOC31 was positive in 100% ADC, 67% SCC, and 35% MM cases. Similarly, mesothelin antibody stained 100% ADC, 60% SCC, and 47% MM cases. Antibodies for K903 and CK5/6 stained 100% SCC cases but fewer ADC cases (40 and 10%, respectively). In conclusion, in this cohort of mostly pleural malignant effusion,
MM can be identified with positive staining for WT-1 and negative staining for p63. Conversely, negative staining with WT-1 and positive staining for p63 exclude MM. Used as part of an immunostain panel, cytokeratin markers (CK5/6 and K903) are useful in differentiating SCC from ADC when MM is already excluded, and MOC31 might have limited value in differentiating ADC from MM. A negative stain with MOC31 can exclude lung ADC. Mesothelin, on the other hand, is not useful in the differential diagnosis of ADC, SCC, and MM.

Keywords: malignant effusion, adenocarcinoma, squamous cell carcinoma, mesothelioma, WT-1, p63, MOC31, mesothelin, K903, CK5/6