Diagnostic value of MUC4 immunostaining in distinguishing epithelial mesothelioma and lung adenocarcinoma

Abstract

The distinction between pleural malignant mesothelioma and pleural infiltration by adenocarcinomas has complex therapeutic and medicolegal implications. Although the panel of adenocarcinoma-associated antibodies and one or two mesothelioma markers is useful in this purpose, most of these antibodies are not totally specific. We determined the diagnostic value of MUC4 immunostaining in this issue. MUC4 gene expression was also studied by in situ hybridization and RT-PCR. MUC4 is a membrane-bound mucin that has been suggested to be implicated in malignant progression in humans and rats. The MUC4 gene is expressed in various normal epithelial tissues of endodermic origin and carcinomas. In the respiratory tract, MUC4 transcripts have been detected in normal respiratory epithelium and lung carcinomas. MUC4 protein was expressed in 32 of 35 (91.4%) lung adenocarcinomas on paraffin-embedded tissue. None of the 41 malignant mesotheliomas nor the 32 cases of benign mesothelial cells expressed MUC4 at the protein and mRNA levels. We conclude that MUC4 is a very specific (100%) and sensitive (91.4%) marker of lung adenocarcinomas on paraffin-embedded tissue that could be useful in diagnostic practice in the distinction between malignant mesothelioma and adenocarcinoma.

Gene Expression Signatures Differentiate Ovarian/Peritoneal Serous Carcinoma from Diffuse Malignant Peritoneal Mesothelioma

“…Further research is, therefore, necessary to establish the clinical role of MUC4 in ovarian cancer. The significantly higher expression level of MUC4 in OC/PPC compared with DMPM is in agreement with the role of this molecule in differentiating lung adenocarcinoma from pleural mesothelioma (30). It is noteworthy that MUC4 is transactivated by PEA3 (31), a member of the Ets transcription factor family whose expression levels correlate with poor survival in patients with OC/PPC effusions (32).…”

Emerging Roles of MUC4 in Cancer: A Novel Target for Diagnosis and Therapy

“…4), in others (invasive ductal carcinoma of the pancreas, intrahepatic cholangiocarcinoma, and extrahepatic bile duct carcinoma), it was related to a poor clinical outcome (5-7). Another important aspect of MUC4 was recognized in distinguishing epithelial mesothelioma from invading lung adenocarcinoma (8). The distinction between the two malignancies is complicated due to the wide range of growth pattern of mesothelioma, a mesenchymally derived cancer with epithelial, fibrous, or mixed morphologic features.…”

“…The distinction between the two malignancies is complicated due to the wide range of growth pattern of mesothelioma, a mesenchymally derived cancer with epithelial, fibrous, or mixed morphologic features. Immunohistochemical analysis showed that MUC4 is overexpressed in lung adenocarcinoma and is useful in distinguishing lung adenocarcinoma from malignant mesothelioma, with 91.4% sensitivity and 100% specificity (8).…”

MUC4 potentiates invasion and metastasis of pancreatic cancer cells through stabilization of fibroblast growth factor receptor 1

“…MUC4 is a large membrane-anchored glycoprotein that is aberrantly expressed in many cancers (12)(13)(14)(15)(16)(17)(18). Its expression is undetectable in the normal pancreas but increases progressively in pancreatic intraepithelial neoplasia (19,20) and is strongly expressed in PC (20)(21)(22)(23).…”