Epithelioid sarcoma: New insights based on an extended immunohistochemical analysis

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

Gamma-Catenin

Gamma-catenin was expressed in 35 of 74 tumors (47%) in a membranous and/or cytoplasmic pattern (Figure 3, D). No nuclear staining was identified. Expression was observed in 53% of the classic ESs, 3 of 7 angiomatoid ESs, and 1 of 5 examples each of the fibroma-like and large cell/rhabdoid variants. The incidence of positivity was variable, but 20 of the 35 positive cases exhibited reaction in over 25% of lesional cells.

Stem Cell Markers

Reaction with antibodies to the tyrosine kinase receptor, Kit, was observed in 5 of 37 cases of ES (14%) and was limited to the classic variants. Although staining was observed in only rare cells in 4 tumors, diffuse cytoplasmic reactivity, albeit weak, was noted in 1 case.

Epithelial stem cell marker, p63, was focally expressed in nuclei of cells in 2 classic ESs and 1 angiomatoid ES, whereas the remaining 17 cases were negative (Figure 3, E). In comparison, all 9 examples of invasive squamous cell carcinoma of the skin showed strong and widespread expression of the molecule (Figure 3, F).

Other Surface Membrane Markers

Epithelial specific antigen was expressed in 10 of 74 (14%) tumors evaluated (Figure 3, G). In 6 of the cases, 10% or less of cells reacted, whereas in 2 classic variants and 1 large cell/rhabdoid ES, over 25% of tumor cells were positive. Membrane expression of this surface molecule was found in 5 classic variants, 3 of 5 examples of large cell/rhabdoid ESs, 1 of 5 fibroma-like ESs, and 1 of 7 angiomatoid variants. Two tumors (both classic ESs) of the 64 tumors tested showed rare cells immunoreactive for mesothelin. Expression of CD10 was observed in rare tumor cells in 1 classic ES, while the remaining 40 tumors tested were negative.

Calretinin

The calcium-binding protein, calretinin, was expressed in nuclei and cytoplasm of 8 of the 40 tumors (20%) evaluated. In 6 of these cases, including the 3 positive large cell/rhabdoid ESs, 10% or less of cells were positive. Strong expression of calretinin was observed in 1 classic ES (Figure 3, H).

COMMENTS

ES is one of only a handful of soft-tissue neoplasms that characteristically shows convincing immunohistochemical expression of keratin. As a vital cytoskeletal protein, keratin is found as a heterodimer consisting of a smaller and acidic (type I) unit and a larger and basic (type II) unit.33 The pairing of the two-keratin subunits results in a heterodimer that is relatively specific for a given epithelial cell line and usually exhibits lineage fidelity in malignantly transformed epithelial cells.34 This principle serves as the basis for the current diagnostic practice of evaluating the immunoexpression of specific keratins when determining site of origin of a carcinoma.

Previous studies have documented immunohistochemical expression of a number of specific keratin subunits in ES. In common with most carcinomas derived from simple epithelia or parenchymal cells and a number of mesenchymal neoplasms, ES has been shown to express simple epithelial keratins 8 and 18 either by positive reactivity for separate monoclonal antibodies18,23,24,25 or for the antibody CAM5.2.8,15,20,22,23 Although K 19 expression has been reported in cases of ES,8,23 expression of K 7, which is typically paired with K 19, has been documented in only scattered cells in less than 20% of tumors tested.8,24,25,35 Immunohistochemical expression of other keratin subunits including lower-molecular-weight keratins K 16 and 17,8,25 intermediate-sized keratins K 13 and 14,8,24,25 and higher-molecular-weight keratins K 4, 6, and 10,25 has also been described in ES.