p40 is a more specific marker than p63 for cutaneous poorly differentiated squamous cell carcinoma.

Poorly differentiated squamous cell carcinoma (SCC) of the skin may pose a diagnostic challenge for pathologists. p40 is a recently introduced antibody that recognizes specific p63 protein isoforms and has shown superior results labeling non-cutaneous SCC. We hypothesize that p40 may improve diagnostic accuracy of poorly differentiated SCC. Twelve cases of poorly differentiated SCC were stained with p63, p40 and cytokeratin MNF116. Control cases included nine atypical fibroxanthoma (AFX), five cutaneous leiomyosarcoma (LMS) and three giant cell tumors of soft tissue (GCTST). All 12 cases labeled with p63 and p40 and 11/12 were positive with MNF116. Whereas p40 labeled fewer cells, it showed exclusive nuclear staining, with no staining of cytoplasm or of background cells, in contrast to p63. Six of nine AFX and 2 of 3 GCTST showed scattered nuclear staining with p63 but were negative with p40. Additionally, one LMS showed focal staining with MNF116 but was negative with p40. For the diagnosis of cutaneous poorly differentiated SCC, p40 appears equally sensitive to MNF116 and p63. While labeling fewer cells, p40 labels without confounding staining of tumor cytoplasm or background cells. More importantly, p40 appears to be more specific for SCC than p63 and MNF116, each of which occasionally labels non-squamous tumors.