*3.3.2.3 Methylthioadenosine phosphorylase (MTAP)*

MTAP is located in the 9p21.3 locus and is often deleted with p16. Detection of homozygous deletion of the 9p21.3 region by p16-fluorescence in situ hybridization is a reliable marker for malignancy in mesothelial effusions. MTAP IC has been suggested as a good surrogate marker for 9p21.3 deletion in surgical and cytology specimens [48]. The association of MTAP and BAP1 IC staining loss can reportedly detect mesothelioma with 78% sensitivity [49]. Only cytoplasmic loss of MTAP should be interpreted as a true loss of expression [48, 49].

### *3.3.2.4 Desmin*

Since benign mesothelial cells express desmin, reactive proliferative mesothelial cells also express desmin in 84%−92% cases, whereas mesothelioma cells only in 0%−6% [30, 50]. Mesothelial cells tend to lose their cytoplasmic desmin expression as they transition to malignancy [22]. Attention has to be paid that any malignant effusion with mesothelioma still has few background reactive mesothelial cells which still are expressing desmin.

### *3.3.2.5 Epithelial membrane antigen (EMA)*

EMA is expressed in adenocarcinoma with a very high sensitivity 91%−100% and a specificity of 86%−100% in differentiating adenocarcinoma from reactive mesothelial cells in effusions [51, 52]. EMA has distinctive staining of the cytoplasmic membrane brush border in mesothelioma, while it exhibits a diffuse cytoplasmic staining pattern in carcinomas [53].

### *3.3.3 Carcinoma markers*

Due to close morphological resemblance, mesothelioma most often has to be differentiated from adenocarcinoma, but depending on location, many other types of carcinoma may be considered diagnostically important. The IC markers are serving two purposes: 1) distinguish broadly carcinoma cells from mesothelial malignancy and 2) differentiate carcinomas of a specific type or location.
