Differentiation of adenocarcinoma of the lung and malignant mesothelioma: predictive value and reproducibility of immunoreactive antibodies

Abstract

A panel of antibodies against keratins, epithelial membrane antigen (EMA), epithelial antigen (Ber-EP4), carcinoembryonic antigen (CEA), tumour-associated glycoprotein (B72.3), vimentin and LeuM1 was applied to sections of adenocarcinoma of the lung and malignant mesothelioma in a randomized design. The proportion of stained tumour cells within each section was estimated independently in five categories by three pathologists (no positive tumour cells, 1-10%, 11-33%, 34-66% and more than 67% positive tumour cells). The kappa values representing the chance corrected interobserver agreement for the different antibodies in such a five group assessment were between 0.38 and 0.72. In two group assessment the kappa values were between 0.53 and 0.94. Nosological sensitivity and nosological specificity were calculated for all antibodies, and diagnostic sensitivity and diagnostic specificity (predictive values) were calculated for the Ber-EP4, CEA, B72.3, LeuM1 and vimentin. The difference between nosological sensitivity and nosologic specificity and the clinically relevant predictive values of positive and negative tests were demonstrated. In respect of the reproducibility and the diagnostic power defined by the predictive values, we demonstrated that a panel of antibodies, including CEA, Ber-EP4 and B72.3 and, to a lesser degree, LeuM1 and vimentin is applicable for the histopathological distinction between adenocarcinoma of the lung and malignant mesotheliomas. Before introduction of new diagnostic tests, including new antibodies, the prevalence of the tested tumours should be estimated. Nosological sensitivity and nosological specificity should be converted to predictive values.

Immunohistochemistry in the distinction between malignant mesothelioma and pulmonary adenocarcinoma: a critical evaluation of new antibodies

“…Our current study supports the findings of previous series and shows that no single antibody is entirely satisfactory in this regard. [20][21][22][23][24] Although it seems that LeuM1 may be most specific because it did not stain mesotheliomas, it also failed to stain six of the 11 adenocarcinomas and is therefore less sensitive than the other antibodies. BerEP4 is the most sensitive of the three but at the same time is the least specific.…”

A comparative evaluation of immunohistochemical markers for the differential diagnosis of malignant pleural tumours

“…p (diagnosis) refers to the prevalence of the diagnosis in the material which is being tested (in this case, proportion of carcinoma and mesothelioma in pleural biopsies in which immunohistochemistry is necessary). The prevalence varies from one centre to the other 33 . In our laboratory, the proportion of carcinoma to mesothelioma was 9:1.…”

Comparison of DNA copy number changes in malignant mesothelioma, adenocarcinoma and large-cell anaplastic carcinoma of the lung

“…The differential diagnosis is currently based on various morphological analyses, including a combination of histological and immunohistochemical stains as well as electron microscopy (Brown et al, 1993;Weiss and Battifora, 1993). Generally, a panel of several diagnostic markers is used, the most common being carcinoembryonic antigen (CEA), epithelial antigen (Ber-EP4) and Leu-M1 (Brown et al, 1993;Skov et al, 1994). These markers recognize molecules expressed by epithelial but not by mesothelial cells, and therefore the diagnosis of mesothelioma is based on negative immunohistochemical results.…”