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 SqCC specifically, DSG3 has demonstrated a sensitivity of 85-100%, and an ability to discriminate lung adenocarcinoma (ADC) 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, breast, prostate, and head and neck cancers. p63 [4A4] recognizes both the p63 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 ADC. In contrast, p40 is selectively expressed in lung SqCC, offering an opportunity for improved specificity (5-8). p40 (M) [BC28] recognizes an epitope unique to p40, which may result in diminished reactivity in lung ADC and increased specificity (8).
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 specimens (4,5).
Napsin A is a pepsin-like aspartic proteinase. It is expressed in most lung adenocarcinomas and some renal cell carcinomas, as well as in type II pneumocytes (4-6). Studies have shown that Napsin A is a more sensitive and specific marker than TTF-1 and is extremely specific for lung ADC versus lung SqCC (4-6).