IMMUNOHISTOCHEMICAL STAINING FOR DESMOGLEINS-1 AND DESMOGLEIN-2 IN KERATINOCYTIC NEOPLASMS WITH SQUAMOUS PHENOTYPE - ACTINIC KERATOSIS, KERATOACANTHOMA AND SQUAMOUS-CELL CARCINOMA OF THE SKIN

Desmosomes are intercellular junctions that have been shown to be down -regulated in certain types of carcinoma and that may play a role in s uppression of invasion and metastasis. This paper describes an immunoh istochemical study of three types of epidermal neoplasms with monoclon al antibody to desmoglein in order to determine how desmosomal stainin g correlates with the clinical, biological and histopathological featu res of these neoplasms. Actinic keratosis (AK) is the most common kera tinocytic premalignant neoplasm that was reported to have a 10-20% rat e of malignant transformation into squamous cell carcinoma (SCC). Kera toacanthoma (KA) is a benign neoplasm that involutes spontaneously aft er a few months of rapid growth. SCC is a malignant tumour capable of metastasis. Electron microscope studies of KA and SCC showed significa ntly reduced staining for desmosomes in SCC but not in KA. We have exa mined staining for desmoglein using the monoclonal antibody 33-3D, a m ouse IgM monoclonal antibody, that recognizes the cytoplasmic domains of desmoglein (Dsg)1 and Dsg2 on frozen sections. Immunohistochemical staining of normal skin with this antibody revealed strong pericellula r localization of the antigen, outlining the cell membranes of the ker atinocytes. A series of 30 AKs, 12 KAs and 24 SCCs was stained immunoh istochemically with 33-3D monoclonal antibody. All examined KAs showed extensive pericellular staining for Dsg. By contrast, juxtanuclear st aining for Dsg was noted in 12 SCCs, and completely negative staining in seven SCCs. The five remaining SCCs showed focal pericellular stain ing for the Dsg marker. The most common finding in AK was focal perice llular staining for Dsg, with complete absence of staining in dysplast ic areas (25 cases). in five cases negative pericellular staining in d ysplastic areas was associated with juxtanuclear accumulation of the D sg marker. A strong negative correlation between Dsg staining and degr ee of dysplasia was obtained. The Dsg pattern in KA is similar to norm al epidermis and shows a clear difference between KA and SCC. AK has a limited loss of Dsg expression in a SCC-like pattern that is congruen t with its premalignant nature. As the stain works on frozen tissue, i t may be helpful for rapid differentiation in selected cases in cutane ous oncology and Mohs micrographic surgery. This antibody may also hav e great potential for the detection of the effects of chemopreventive agents in skin cancer.