Epithelioid sarcoma: New insights based on an extended immunohistochemical analysis

Archives of Pathology & Laboratory Medicine, Sep 2003 by Laskin, William B, Miettinen, Markku

The p63 gene found on chromosome 3q27 has structural homology with p53 and as a result is considered a putative tumor suppressor gene.46 The gene encodes a number of isoforms that are divided into those that share transactivating functions with p53 and those that suppress these functions. The latter group of p63 molecules is thought to help maintain the stem/basal cell population and is found in basal (stem) cells of stratified epithelia, hair follicles, skin, and prostate, and in myoepithelial cells of the salivary gland and breast.46 Because p63 is expressed in squamous cell carcinoma of the skin,47 we wondered if nuclear expression of this molecule could assist in differentiating ES from the latter. We found focal expression of p63 in 2 classic and 1 angiomatoid ES, whereas diffuse, strong expression was identified in all 9 examples of invasive cutaneous squamous cell carcinoma evaluated for comparison. Our results indicate that an immunohistochemical panel of p63 and CK 5/6 will successfully separate ES (usually negative) from invasive cutaneous squamous cell carcinoma (strongly positive).

Mesothelin and epithelial-specific antigen are 40-kD differential cell surface glycoproteins for which a number of antibodies have been developed for immunohistochemistry. Epithelial-specific antigen probably functions in cell-to-matrix adhesion.48 Antiepithelial-specific antigen reacts strongly with virtually all epithelial cells and in a wide range of carcinomas, but weakly with mesothelial cells, making it a useful addition to an immunohistochemical battery for distinguishing mesothelioma from carcinoma.49 In our study, epithelial-specific antigen was variably expressed in 14% of the 74 tumors evaluated. However, because 3 of the 5 large cell/rhabdoid variants were positive, we warn against using this antibody alone in attempting to differentiate this ES variant from carcinoma. Mesothelin is a highly sensitive marker for epithelial mesothelioma, but is also expressed in most surface ovarian carcinomas, ductal adenocarcinoma of the pancreas, and squamous cell carcinoma.50-53 Its function to date is unknown. In our study, only rare tumor cells were positive for mesothelin in 2 of the 64 cases tested. As immunohistochemical expression of this protein was reported in all 44 epithelial mesotheliomas tested in 1 study,53 antimesothelin could potentially assist in separating large cell/rhabdoid ES from the latter.

CD10, also known as the common acute lymphoblastic lymphoma antigen (cALLa), is a cell surface neutral endopeptidase that is a well-recognized marker used in the evaluation of acute lymphoblastic leukemia. The molecule has also been identified in nonhematopoietic tumors, including carcinomas, melanomas, and a number of mesenchymal neoplasms.54 In the normal dermis, CD10 is expressed in a population of periadnexal dendritic fibroblast-like cells.55 Immunoexpression of CD10 has been observed in the dermal-based tumor, dermatofibroma (fibrous histiocytoma), and to a lesser extent in dermatofibrosarcoma protuberans, neurofibroma, and primary melanoma.55 We explored the potential use of using CD10 in distinguishing ES (especially those tumors with a significant spindle cell component) from dermatofibroma (fibrous histiocytoma). Except for 1 classic ES, in which a rare cell was positive, the remaining 40 cases, including 3 examples of the fibroma-like variant, were negative. These results support the use of CD10 (along with keratin and CD34) to help separate ES from dermatofibroma (fibrous histiocytoma).