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

Abstract

The differential diagnosis of epithelioid mesothelioma from lung adenocarcinoma and squamous cell carcinoma requires the positive and negative immunohistochemical markers of mesothelioma. The IMIG guideline has suggested the use of Calretinin, D2-40, WT1, and CK5/6 as mesothelial markers, TTF-1, Napsin-A, Claudin 4, CEA as lung adenocarcinoma markers p40, p63, CK5/6, MOC-31 as squamous cell markers. However, use of other immunohistochemical markers is still necessary. We evaluated 65 epithelioid mesotheliomas, 60 adenocarcinomas, and 57 squamous cell carcinomas of the lung for MUC4 expression by immunohistochemistry and compared with the previously known immunohistochemical markers. MUC4 expression was not found in any of 65 cases of epithelioid mesothelioma. In contrast, MUC4 expression was observed in 50/60(83.3%) cases of lung adenocarcinoma and 50/56(89.3%) cases of lung squamous cell carcinoma. The negative MUC4 expression showed 100% sensitivity, 86.2% specificity and accuracy rate of 91.2% to differentiate epithelioid mesothelioma from lung carcinoma. The sensitivity, specificity, and accuracy of MUC4 are comparable to that of previously known markers of lung adenocarcinoma and squamous cell carcinoma, namely CEA, Claudin 4 and better than that of MOC-31. In conclusion, MUC4 immunohistochemistry is useful for differentiation of epithelioid mesothelioma from lung carcinoma, either adenocarcinoma or squamous cell carcinoma.

Mucin 21 is a novel, negative immunohistochemical marker for epithelioid mesothelioma for its differentiation from lung adenocarcinoma

“…CEACAM6 and NAPSA are known to encode CEA and napsin-A, respectively, and we recently reported the efficacy of MUC4 as a negative immunohistochemical marker for the differentiation of epithelioid mesothelioma from non-small-cell lung carcinoma, either adenocarcinoma or squamous cell carcinoma. 15 Reanalysis of the microarray data from a previous study 13 was performed to generate the scatter plot, line graph and hierarchical clustering of statistically significant genes with more than a two-fold change between epithelioid mesothelioma and lung adenocarcinoma. MUC21 was identified as a novel gene of interest for further study of its utility as a basis for a negative immunohistochemical marker of epithelioid mesothelioma to differentiate it from lung adenocarcinoma.…”

“…Sections were incubated with the primary antibody for 2 h at room temperature, and this was followed by amplification with an Amplification Kit (Ventana). CEA, claudin‐4, TTF‐1, napsin‐A and mucin 4 (MUC4) immunohistochemistry was performed as previously described …”

“…CEA, claudin-4, TTF-1, napsin-A and mucin 4 (MUC4) immunohistochemistry was performed as previously described. 15 Immunoreactivity was evaluated as negative or positive. Nuclear staining with TTF-1, cytoplasmic staining with CEA, napsin-A and MUC4 and membranous staining with claudin-4 and MUC21 were considered to indicate positivity.…”

Ancillary studies in pleural, pericardial, and peritoneal effusion cytology

“…[13][14][15] Although Ber-EP4 and MOC-31 are reasonably sensitive as adenocarcinoma markers, both demonstrate positive staining in a subset of epithelioid mesotheliomas, which represents a potential diagnostic pitfall in effusion specimens. 14,15 A study found no membranous staining in 75 malignant mesotheliomas, although 11% (8 of 75 cases) had weak cytoplasmic staining, which is considered nonspecific. 12 In our practice, we no longer routinely use Ber-EP4 or MOC-31 because we have found claudin 4 to be more useful.…”

“…Claudin 4 shows improved sensitivity and specificity over Ber‐EP4 and MOC‐31 for distinguishing adenocarcinoma from cells of mesothelial origin . Although Ber‐EP4 and MOC‐31 are reasonably sensitive as adenocarcinoma markers, both demonstrate positive staining in a subset of epithelioid mesotheliomas, which represents a potential diagnostic pitfall in effusion specimens . A study found no membranous staining in 75 malignant mesotheliomas, although 11% (8 of 75 cases) had weak cytoplasmic staining, which is considered nonspecific .…”