MUC4, a novel immunohistochemical marker identified by gene expression profiling, differentiates pleural sarcomatoid mesothelioma from lung sarcomatoid carcinoma

Abstract

Sarcomatoid mesothelioma, a histological subtype of malignant pleural mesothelioma, is a very aggressive tumor with a poor prognosis. Histological diagnosis of sarcomatoid mesothelioma largely depends on the histomorphological feature of spindled tumor cells with immunohistochemical reactivity to cytokeratins. Diagnosis also requires clinico-radiological and/or macroscopic evidence of an extrapulmonary location to differentiate it from lung sarcomatoid carcinoma. Although there are promising immunohistochemical antibody panels to differentiate mesothelioma from lung carcinoma, a consensus on the immunohistochemical markers that distinguish sarcomatoid mesothelioma from lung sarcomatoid carcinoma has not been reached and requires further study. We performed whole gene expression analysis of formalin-fixed paraffin-embedded tissue from sarcomatoid mesothelioma and lung sarcomatoid carcinoma and observed significant differences in the expression of MUC4 and other genes between sarcomatoid mesothelioma and lung sarcomatoid carcinoma. Immunohistochemistry demonstrated that MUC4 was expressed in the spindled tumor cells of lung sarcomatoid carcinoma (21/29, 72%) but was not expressed in any sarcomatoid mesothelioma (0/31, 0%). To differentiate sarcomatoid mesothelioma from lung sarcomatoid carcinoma, negative MUC4 expression showed 100% sensitivity and 72% specificity and accuracy rate of 87%, which is higher than immunohistochemical markers such as calretinin, D2-40 and Claudin-4. Therefore, we recommend to include MUC4 as a novel and useful negative immunohistochemical marker for differentiating sarcomatoid mesothelioma from lung sarcomatoid carcinoma.

MUC4 immunohistochemistry is useful in distinguishing epithelioid mesothelioma from adenocarcinoma and squamous cell carcinoma of the lung

“…MUC4 plays a role in cell differentiation rather than cell proliferation of the normal goblet cells, the stratified squamous epithelial cells, and malignant epithelial tumor cells 19 . We previously reported the MUC4 expression in sarcomatoid carcinoma of the lung and its utility to differentiate from sarcomatoid mesothelioma 20 .…”

“…In this study, we analyzed the utility of MUC4 to distinguish epithelioid mesothelioma from lung adenocarcinoma and squamous cell carcinoma. We have previously reported the MUC4 expression in sarcomatoid carcinoma of the lung and its utility to differentiate from sarcomatoid mesothelioma 20 . In our previous report, we emphasized the MUC4 expression in spindled cells of sarcomatoid carcinoma of lung.…”

Diagnostic value of D2-40 immunostaining for malignant mesothelioma: a meta-analysis

“…However, interpretation should be with caution when differentiating pleural MM from lung small cell carcinomas (SCC), because it was reported that D2-40 can stained 77% of lung SCC [ 5 ]. Recently, novel markers, such as BAP1 [ 5 ], MUC4 [ 35 ], fibulin-3 [ 41 ], have been used to improve the diagnostic accuracy of D2-40 for pleural MM.…”

A case of cytokeratin–negative sarcomatoid malignant pleural mesothelioma

“…Cytokeratin and other positive markers of MPM were negative, and no specific tendency for differentiation was noted. For differentiation from lung sarcomatoid carcinoma, we performed MUC4 and GATA binding protein 3 (GATA3) staining . MUC4 was negative and GATA3 was partially positive (Fig.…”

“…Recently, however, it was reported that MUC4 and GATA3 are useful for such differentiation. Amatya et al . found that MUC4 was expressed in 0 of the 31 sarcomatoid MPM and in 21 of the 29 lung sarcomatoid carcinoma (5 cases of spindle cell carcinoma and 24 of pleomorphic carcinoma).…”