Desmoglein 3 (DSG3) is a calcium-binding transmembrane glycoprotein component of desmosomes in vertebrate epithelial cells. Currently, three desmoglein subfamily members have been identified and all are members of the cadherin cell adhesion molecule superfamily (1,2). Desmogleins exhibit membranous expression and connect with cytokeratins through desmoplakins and plakoglobin. DSG3 is particularly important in the cellular adhesion of squamous epithelium, and as a result, it is often highly expressed in various squamous cell carcinomas (SqCC) (3). In lung squamous cell carcinoma specifically, DSG3 has demonstrated a sensitivity of 85-100%, and an ability to discriminate lung adenocarcinoma with a specificity of 98-100% (3-6).
The mouse monoclonal antibody p40 [BC28] recognizes an epitope unique to the p40 protein and may have applications in cases where p63 has traditionally been used. To date, p63 [4A4] has been a frequently used marker for lung SqCC, as well as for bladder,and p40 proteins (7). As a result, p63 [4A4] has proven to be a sensitive marker for lung SqCC; however, it suffers from specificity limitations due to reactivity in a subset of lung adenocarcinomas (ADC). In contrast, p40 is selectively expressed in lung SqCC, offering an opportunity for improved specificity (5,7,8). p40 (M) [BC28] recognizes an epitope unique to p40, which may result in diminished reactivity in lung ADC and increased specificity.
In several studies, staining with a rabbit polyclonal anti-p40 antibody was equivalent to p63 [4A4] in sensitivity for lung SqCC, but p40 exhibited markedly superior specificity due to staining in fewer cases of lung ADC compared to p63 (5,7-9). In an in-house study, Biocare’s mouse monoclonal anti-p40 [BC28] demonstrated similar sensitivity and specificity as the rabbit polyclonal antibody, staining 97% (65/67) of lung SqCC cases and 0% (0/71) of lung ADC cases; however, p40 expression may be observed with either antibody in select cases of lung ADC. The combination of both membrane and nuclear staining of DSG3 and p40, respectively, may increase overall sensitivity for lung SqCC, and in some cases, may aid the pathologist with difficult cytology and surgical specimens (5).