Utility of a Highly Specific and Sensitive Podoplanin/D2-40, Calretinin, Thyroid Transcription Factor-1, and Carcinoembryonic Antigen/CD66e Immunohistochemical Panel in Differentiating Malignant Pleural Mesothelioma from Metastatic Adenocarcinoma: An Egyptian Experience.

Background and objective: Considering plentiful immunohistochemical (IHC) antibodies, a selection of highly sensitive and specific targeted panels is necessary to differentiate malignant pleural mesothelioma (MPM) from metastatic adenocarcinoma. We aimed to examine the sensitivity and specificity of four markers (podoplanin [PDPN]/D2-40, calretinin, thyroid transcription factor-1 [TTF-1], and carcinoembryonic antigen [CEA]/CD66e) as an initial IHC panel of Egyptian patients with malignant pleural biopsies.

Materials and methods: Forty Egyptian malignant pleural biopsies with histomorphological features of mesothelioma versus adenocarcinoma were immunohistochemically stained by PDPN/D2-40, calretinin, TTF-1, and CEA/CD66e.

Results: PDPN/D2-40 and calretinin were positive in 27/27, 100% of mesothelioma cases with 100% sensitivity, 96.4% specificity for PDPN/D2-40, and 100% sensitivity and specificity for calretinin. Membranous PDPN/D2-40 expression was strong in 14 cases (53.85%), moderate in eight cases (30.77%), and weak in four cases (15.38%), while pure cytoplasmic staining was reported in one case. Calretinin was predominantly nuclear in all mesothelioma cases. TTF1 and CEA/CD66e were negative in all mesothelioma cases. In adenocarcinomas, PDPN/D2-40 was only expressed as weak cytoplasmic staining in 1/13 cases, while calretinin was negative in all 13 cases. Nuclear TTF1 and cytoplasmic CEA/CD66e immunostaining positivity were reported in all adenocarcinoma cases (13/13) with 100% sensitivity and specificity for both markers.

Conclusion: The combination of PDPN/D2-40, calretinin together with CEA/CD66e, and TTF1 may be highly valuable in differentiating MPM from metastatic adenocarcinoma.