Claudin-4 Immunohistochemistry Is Highly Effective in Distinguishing Adenocarcinoma from Malignant Mesothelioma in Effusion Cytology
Vickie Y Jo, Edmund S Cibas, Geraldine S Pinkus. Brigham and Women's Hospital, Harvard Medical School, Boston, MA
Background: Adenocarcinoma (ACA) can be challenging to distinguish from malignant mesothelioma in effusions, and often requires ancillary studies and clinical data. Immunohistochemical panels, including calretinin, WT-1, EMA, AE1/AE3, MOC31, BerEP4, and B72.3, are useful but can yield varying results. Immunohistochemistry for claudin-4, a tight-junction associated protein, has recently been shown to distinguish ACA from malignant mesothelioma, mostly in surgical specimens. Our aim is to validate and assess immunoreactivity for claudin-4 staining in a large series of malignant effusions.
Design: 148 malignant effusions (84 ACA, 64 malignant mesothelioma) diagnosed between 2008-2012 were retrieved from the cytopathology files. Medical records and pathology reports were reviewed for each case. For all cases of ACA, either a known primary or confirmatory IHC were required for inclusion. For all malignant mesotheliomas, concurrent confirmatory studies were required (biopsy/resection, cytogenetics, or immunohistochemical studies). Immunohistochemistry was performed on cell block sections following heat-induced epitope retrieval (EDTA/steamer) using a monoclonal antibody to claudin-4 (clone 3E2C1) and an immunoperoxidase technique. Moderate-to-strong membranous staining in greater than 50% of tumor cells was considered a "positive" result. Absent or weak/focal cytoplasmic staining was considered "negative."
Results: 64 cases of mesothelioma and 84 ACA (31 lung, 2 esophageal, 2 gastric, 4 colon, 1 appendix, 3 pancreas, 15 ovarian, 24 breast, 1 prostate, 1 unknown primary) were evaluated. 83 cases of ACA were positive for claudin-4 (99%); 1 case of serous carcinoma was negative. Most cases of ACA showed strong and diffuse membranous staining (71/84; 84%); 12 (14%) cases showed membranous staining of moderate intensity. All cases of mesothelioma were negative for claudin-4.
Conclusions: Claudin-4 immunohistochemistry effectively distinguishes ACA from malignant mesothelioma with high sensitivity and specificity. Addition of claudin-4 to the typical immunohistochemical panel when encountered with a challenging malignant effusion has high utility. In addition, the characteristic strong staining pattern may be useful in detecting malignant ACA cells in samples with scant cellularity.
Monday, March 4, 2013 1:00 PM
Poster Session II # 71, Monday Afternoon