The Use of Immunohistochemical Detection of Carbonic Anhydrase lX, M2A Oncofetal Antigen, and lnhibitor of Apoptosis Proteins for the Histological Diagnosis of Malignant Pleural Mesothelioma

Abstract

Malignant pleural mesothelioma is an aggressive neoplasm arising the pleural lining of the lungs. Diagnosis of this condition can sometimes be difficult from cytological and histological appearance alone, as it can be found to resemble benign, reactive or hyperplastic mesothelial cells, or metastatic adenocarcinoma. In difficult cases immunohistochemistry is used to stain markers that can differentiate between these conditions. Correct diagnosis of mesothelioma is important to treatment of the disease and can have legal implications due to its link with industry. In this study pleural biopsies containing malignant mesothelioma, metastatic adenocarcinoma or benign mesothelial cells were examined for the production of the proteins M2A Oncofetal Antigen, Carbonic Anhydrase lX (CA lX), and the lnhibitor of Apoptosis Proteins XIAP and IAP-L. M2A Oncofetal Antigen was assessed for use in differentiating between mesothelial cells and adenocarcinoma, while CA lX, XIAP and IAPL were all assessed to see if they were suitable for differentiating between benign and malignant cells. L41 pleural biopsies (46 containing benign mesothelial cells, 42 containing malignant mesothelioma, and 43 containing metastatic adenoca rcinoma) were selected from archived formalin fixed, paraffin wax processed surgical tissue blocks. Sections from these blocks were stained immunohistochemically using antibodies against human M2A oncofetal antigen, CA lX, XIAP and IAP-I. The staining intensity in tumour cells was graded from g(negative) to 3+ and the percentage of each cell population staining at these levels was recorded. From these results, the sensitivity and specificity of each marker was calculated. This study found that M2A oncofetal antigen staining using the D2-40 antibody was positive in a high proportion of cells of mesothelial origin, but negative in a high proportion of adenocarcinomas, making it a very good marker of mesothelial cells. However, caution is advised due to background connective tissue staining and it is advised that M2A oncofetal antigen staining is used as part of a panel of antibodies' The three antibodies assessed with regard to differentiating between benign and malignant cells were shown to be neither sensitive nor specific enough to be of any use in this task. XlAp and CA lX, however, may possibly have a role to play in determining the prognosis of a patient, due to stronger and more frequent staining in epithelioid mesothelioma than in the sarcomatoid form.