Immunocytochemistry in the differential diagnosis of serous effusions

Abstract

BACKGROUND The distinction between pleural mesothelioma (MS), reactive mesothelium (RM), and adenocarcinoma (AC) in serous effusions continues as a diagnostic problem in pathology. Immunohistochemistry can help, especially in surgical samples, but the optimum panel of antibodies has yet to be reported. The application of these antibodies to serous effusions has displayed variable results. The aim of this study was to evaluate the usefulness of eight monoclonal antibodies in the differential diagnosis of MS, RM, and AC in serous effusions. METHODS A total of 44 cytologic specimens of serous effusions (26 pleural, 15 peritoneal, and 3 pericardial) from 30 ACs, 3 MSs, and 11 RMs, previously stained with Papanicolaou stain, were selected retrospectively from our files and stained with HBME‐1, thrombomodulin, calretinin, MOC‐31, Ber‐EP4, E‐cadherin, CEA, and CD‐15. The immunoreactions were evaluated independently by two pathologists. A stepwise logistic regression analysis was applied to the data to select an appropriate panel of antibodies. RESULTS Statistical significance was found with HBME‐1, thrombomodulin, MOC‐31, Ber‐EP4, and CD‐15, when comparing both AC versus MS, and AC versus any type of mesothelial proliferation (MS or RM). Using HBME‐1, 80% of ACs were negative whereas all three MSs reacted strongly with P = 0.003. A P = 0.02 was reached with thrombomodulin with 76.5% of ACs showing no immunoreactivity. Ber‐EP4 and MOC‐31 displayed good results with a P < 0.001 and 0.01, respectively. CD‐15 reached a P = 0.034. No differences were found using the other antibodies. Ten ACs, all 3 MSs, and 10 RMs were double immunostained with HBME‐1 and/or MOC‐31 and Ber‐EP4 successfully. CONCLUSIONS Immunohistochemical studies performed on Papanicolaou stained cytologic smears proved to be useful in the differentiation between metastatic AC and mesothelial proliferation. HBME‐1, thrombomodulin, MOC‐31, Ber‐EP4, and CD‐15 were the most useful. In selected cases, it appeared that double immunostaining aided the differential diagnosis. Cancer (Cancer Cytopathol) 2001;93:68–72. © 2001 American Cancer Society.

Snail, Slug, and Smad‐interacting protein 1 as novel parameters of disease aggressiveness in metastatic ovarian and breast carcinoma

“…Analysis of E‐cadherin expression in malignant effusions from patients with gastric and pancreatic carcinoma showed reduced expression of this adhesion molecule in the majority of specimens 53. In contrast, three recent studies showed frequent expression of this molecule in carcinoma cells of various origins (breast, lung, ovary, gastrointestinal tract) in effusions 15, 54, 55. It is interesting to note that an analysis of 4 breast carcinoma effusions showed staining in < 10% of cells in all specimens 54.…”

Ber-EP4 and Anti-Calretinin Antibodies: A Useful Combination for Differential Diagnosis of Various Histological Types of Ovarian Cancer Cells and Mesothelial Cells

“…Although ovarian cancer patients have the highest percentage of malignant peritoneal cytology, which represents the clinical stage, intraperitoneal metastasis and patient survival, the number of the patient specimens was small and insufficient (Khoury 1990;Ordoñez 1998a;Lozano et al 2001;Attanoos et al 2002). Furthermore, these studies examined only serous type but not other histological types of ovarian carcinoma cases.…”

“…Many studies have attempted to apply immunocytochemical staining in the differentiation of these two types of cells. However, large differences exist in the results of these published studies, regarding both the value of some of the markers and which markers should be included in the routine diagnostic panel for differentiating them (Delahaye et al 1997;Fetsch et al 1998;Ordoñez 1998;Lozano et al 2001;Attanoos et al 2002). In addition, previous studies examined only serous type but not other histological types of ovarian carcinoma cases.…”

Diagnostic Accuracy of Ber-EP4 for Metastatic Adenocarcinoma in Serous Effusions: A Meta-Analysis

“…Ber-EP4 is a monoclonal antibody that identifies 34-kD and 39-kD cell surface glycoproteins present on the membrane of human epithelial cells but not on reactive or malignant mesothelial cells [9]. An increasing number of studies have shown the ability of this antibody to be a marker in the differential diagnosis of MAC from MM/RM [1], [10]–[37].…”