The biopsy diagnosis of pleural malignant mesothelioma (MM) can be problematic and requires the use of ancillary techniques more frequently than most other epithelioid tumors. In most laboratories, immunohistochemistry is today the mainstay for the pathological diagnosis of MM. 1-4 Because no single antibody has been identified with 100% sensitivity and 100% specificity for a diagnosis of MM, panels of antibodies that include both positive and negative markers are routinely employed: yet even the most recent and comprehensive of the published studies focus on the sensitivity and specificity of single antibodies investigated independently of the others 4, and numerous recent reviews suggesting various panels of antibodies 5-13 are based on this type of analysis.5, 6, 14 A recent attempt at meta-analysis has been made to provide guidance,9 but because of heterogeneity in the raw data in the individual studies on which the meta-analysis was carried out, the validity of this approach is limited. The same principle applies to the website STATdxPathIq (formerly known as 'Immunoquery'),15 which provides sensitivities and specificities of antibodies, based on published studies, and suggests IHC panels for differential diagnosis based on those data. Only a handful of studies have attempted to use more advanced statistical methods, including logistic regression 1, 2, 16, but the only study attempting to include stepwise logistic regression employed pleural effusion fluids and used a panel of antibodies that included predominantly positive carcinoma markers, relying on lack of labelling for a diagnosis of mesothelioma.
In this current study, a panel of mesothelial-related antibodies and carcinoma-related antibodies, as well as two general epithelial antibodies was used (Table 1) and a multivariate statistical analysis—which involves observation and analysis of more than one variable at a time while taking simultaneously into account the effects of all variates on the endpoint of interest—was carried out.
Therefore, the present study investigated a comprehensive antibody panel jointly. Constructing regression trees may be seen as a type of variate selection procedure. The aim is to differentiate reliably between pleural epithelial MM and secondary adenocarcinoma affecting the pleura. The objective was to ascertain which specific minimal set of markers proved most reliable in making the distinction between these two malignancies and correlating with a diagnosis of MM. This approach allows a rational decision for a minimal set of antibodies as primary line of investigation, which is known to maximize the diagnostic yield. This may reduce the cost of the investigation and the time required for the pathologist to assess the sections—an inconvenient but important rational consideration in a climate of ever increasing pressures associated with time constraints and cost savings. In other words, this approach aims to maximize the number of definitive diagnoses that can be made based on a specific limited panel of antibodies. If no definite diagnosis is reached after using the specified antibody panel, further immunohistochemical studies or other ancillary studies including electron microscopy may then be carried out as necessary.
