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.
|Intensity||LAC (n=60)||Metastatic LAC involving pleura (n=23)||Pleural MM (n=76)|
|Absent||0 (0%)||0 (0%)||76 (100%)|
|Weak||0 (0%)||0 (0%)||0 (0%)|
|Moderate||5 (8%)||6 (26%)||0 (0%)|
|Strong||55 (92%)||17 (73%)||0 (0%)|