Evaluation of a Panel of Molecular Markers for the Diagnosis of Malignant Serous Effusions

Abstract

Purpose: Our main goal was to evaluate a panel of molecular markers for the detection of cancer cells in serous effusions and to determine their value as an adjunctive reverse transcription-PCR (RT-PCR) test to cytologic examination. Experimental Design: One hundred fourteen serous effusions from 71patients with tumors and 43 patients with benign diseases were subjected to RT-PCR for expression of carcinoembryonic antigen (CEA), epithelial cell adhesion molecule (Ep-CAM), E-cadherin, mammaglobin, mucin 1 (MUC1) isoforms MUC1/REP, MUC1/Y, and MUC1/Z, calretinin, and Wilms' tumor 1susceptibility gene. Results: CEA, Ep-CAM, E-cadherin, and mammaglobin were specifically expressed in malignant effusions. The sensitivity of RT-PCR in cytologically negative malignant effusions was 63.1% combining CEA and Ep-CAM (with 100% specificity) and reached 78.9% adding MUC1/Y or MUC1/Z (with 93% specificity). In the whole population of effusions, the combination of cytology with RT-PCR of CEA and Ep-CAM yielded a 90.1% sensitivity, a specificity and a positive predictive value of 100%, and a 86% negative predictive value for malignancy. Adding MUC1/Y or MUC1/Z to the panel, the sensitivity was 94.5% with 93% specificity, 95.7% PPV, and 90.9% negative predictive value. Moreover, CEA and mammaglobin were specifically expressed in epithelial malignancies, and mammaglobin was mainly expressed in effusions from breast carcinoma (97.3% of specificity). Conclusions: A combination of cytology and RT-PCR analysis of CEA and Ep-CAM significantly improved the detection sensitivity of tumor cells in serous effusions. RT-PCR analysis of CEA, Ep-CAM, and mammaglobin in serous effusions could be a beneficial adjunct to cytology for the diagnosis of malignancy.

Diagnostic Utility of MOC-31, HBME-1 and MOC-31mRNA in Distinguishing Between Carcinoma Cells and Reactive Mesothelial Cells in Pleural Effusions

“…7 It has been reported that immunocytochemistry (ICC) and reverse transcriptase polymerase chain reaction (RT-PCR) technique were used to make the distinction between cancer cells and reactive mesothelial cells. 5,8 However, RT-PCR was less intensively used in serous effusions, although it provides excellent material for molecular analysis. In the present study, we combined ICC with RT-PCR for distinguishing between carcinoma cells and reactive mesothelial cells in pleural effusion specimens.…”

Diagnostic Usefulness of MUC1 and MUC4 for Distinguishing between Metastatic Adenocarcinoma Cells and Reactive Mesothelial Cells in Effusion Cell Blocks

“…In previous studies, MUC1 was also detected in benign effusions including RMC. MUC1 mRNAs were expressed in the serous effusions of patients with benign diseases [13,15]. Using the same clone of MUC1 as that used in our study, Creaney et al [17] detected weak or equivocal staining of MUC1 on two thirds of benign RMC from nonmalignant effusions.…”

“…Because MUC1 and MUC4 are expressed mainly by the epithelial cells and are frequently overexpressed in carcinoma cells, it would be reasonable to anticipate its applicability in discriminating MAC from both benign and malignant mesothelial cells. However, studies on the expression of these mucins in body cavity fluids are limited [13,14,15,16,17,18]. Using immunocytochemistry, Han et al [18] analyzed expression of MUC1 in formalin-fixed paraffin-embedded cell blocks prepared from effusion specimens with evidence of metastatic carcinoma.…”

“…However, studies on the expression of these mucins in body cavity fluids are limited [13,14,15,16,17,18]. Using immunocytochemistry, Han et al [18] analyzed expression of MUC1 in 25 effusion specimens with evidence of metastatic carcinoma including 14 ovarian serous carcinomas, 9 pancreatic carcinomas and 2 unknown primaries, and demonstrated that MUC1 immunoreactivity was detected in all cases of pancreatic and ovarian carcinoma.…”

Detection of mRNAs of GA733 Genes by RT-PCR in Exfoliated Cells of Pleural and Peritoneal Effusions and Its Clinical Values

“…Local treatments, such as pleurodesis (2), intraperitoneal chemotherapy (3) and intraperitoneal immunotherapy (4) (15). The criteria for the results were dichotomized: the specific band which appeared in the gel was positive, otherwise negative (16). T a b l e 1 .…”