[1926] Claudin-4: An Effective Immunohistochemical (IHC) Marker Distinguishing Primary and Metastatic Lung Adenocarcinoma from Pleural Epithelioid Malignant Mesothelioma

Anthony S Perry, Geraldine S Pinkus, Joseph M Corson. Brigham and Women's Hospital, Harvard Medical School, Boston, MA

Background: Distinction of metastatic adenocarcinoma from epithelioid malignant mesothelioma (MM) is a well-known diagnostic challenge. Numerous antibodies are useful in this distinction but none with absolute (100%) sensitivity and specificity. Claudin-4, a tight junction protein has recently been reported (Facchetti et al, Virchows Arch. 2007, 451:669-680) as helpful to distinguish lung adenocarcinoma (LAC) and adenocarcinoma of other organs from MM. This study compares the expression of claudin-4 in a large series of LAC (n=83) and pleural epithelioid MM (n=76).
Design: Cases were retrieved from the files of the Brigham and Women's Hospital (Boston, MA) from the period 2005-12 and diagnoses were confirmed. Immunohistochemistry was performed on formalin-fixed paraffin embedded tissue sections following heat-induced epitope retrieval (EDTA/steamer) using a monoclonal antibody to claudin-4 and an immunoperoxidase technique. Appropriate positive (LAC) and negative (isotype control) control slides were processed for all studies. Staining intensity and percentage of cells immunoreactive for claudin-4 was evaluated.
Results: Claudin-4 immunoreactivity was present in all cases (100%) of LAC (primary n=60; metastatic n=23). Most (75-100%) of the neoplastic cells were immunoreactive in 75 cases (90%) of LAC. Claudin-4 reactivity was generally of strong intensity and was expressed in a predominantly membranous pattern. Staining intensity was independent of histologic grade (well differentiated n=7; moderately differentiated n=20; poorly differentiated n=56) and biopsy site (lung n=60; pleura n=23). All 76 cases of mesothelioma were totally negative for membranous reactivity. In this series of cases, the sensitivity and specificity of distinguishing between LAC and MM was 100% for both.

Membranous Claudin-4 Expression
IntensityLAC (n=60)Metastatic LAC involving pleura (n=23)Pleural MM (n=76)
Absent0 (0%)0 (0%)76 (100%)
Weak0 (0%)0 (0%)0 (0%)
Moderate5 (8%)6 (26%)0 (0%)
Strong55 (92%)17 (73%)0 (0%)

Conclusions: This study demonstrates that immunohistochemical expression of Claudin-4 is associated with lung adenocarcinoma, both primary and metastatic, exhibits a strong membranous staining pattern, and is highly effective in distinguising LAC from pleural epithelioid MM.
Category: Pulmonary

Wednesday, March 6, 2013 1:00 PM

Poster Session VI # 284, Wednesday Afternoon


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