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Monoclonal antibody (MCA) 44-3A6 detects a cell-surface transmembrane phosphoprotein frequently expressed by pulmonary adenocarcinoma (AC) and associated with glandular differentiation. This antibody has been found to have utility in assessing routine formalin fixed paraffin-embedded pulmonary neoplasms, as well as the cytopathological evaluation of sputum and bronchial brushings. Recently, it has been shown to be useful in cytological diagnosis of pleural effusions. This study is directed at evaluating its effectiveness in detecting immunoreactive neoplastic cells in body fluids (BF) arising in other tissues. A retrospective cohort of 57 cases was studied, consisting of 36 pleural, 19 ascitic, and 2 pericardial BF. After evaluation of Papanicolaou-stained slides, the BF specimens were immunostained with MCA 44-3A6 using the avidin-biotin-peroxidase complex (ABC) method. In 29 cases, tissue sections of the primary tumors, were also available for immunostaining with MCA 44-3A6. Results showed that 39/42 (93%) of AC BF cases were positive and 28/42 (66%) stained intensely (3-4+) with 75-100% of the AC cells staining in each case. All of the 18 benign and non-AC malignant BF were negative. The staining patterns in the tissue sections of the 29 cases that had corresponding BF samples were similar. We conclude from this study that the MCA 44-3A6 (1) is useful in detecting cells consistent with AC in BF; (2) does not stain inflammatory cells or reactive mesothelial cells, thus helping distinguish reactive from malignant BF; and (3) frequency and pattern of expression in BF parallels its expression in tissue specimens. This study confirms that this MCA is a useful adjunct tool in the cytopathological evaluation of BF.

In this report we describe the expression of the adenocarcinoma associated antigen recognized by the monoclonal antibody 44-3A6, in various tissues during normal human fetal development. Conventional, formalin-fixed and paraffin-embedded sections of normal organs were examined from fetuses ranging from 9 to 42 weeks of gestation. Immunohistochemical localization of antigen-antibody complexes was accomplished using the avidin-biotin complex (ABC) method using horseradish peroxidase. The monoclonal antibody (MAb) 44-3A6 detects a cell surface 40 kD protein which is frequently expressed by adenocarcinomas and by select normal glandular tissues. Detectable expression of this protein was seen at different time periods during fetal development depending on the tissue. This expression was confined to a relatively small range of cell types and tissues; immunostaining was noted in select epithelial cells of the aerodigestive tract, exocrine pancreas, neural tissues, renal tubules, and transitional urothelium, as well as in other tissues. This immunostaining generally, but not invariably, corresponded with patterns previously reported in benign and/or malignant neoplasms of adult tissues. In most instances, once expression occurred within a tissue, it continued through gestation. These data show that this tumor associated gene product is differentially expressed in a broad range of normal developing human fetal tissues.

The IgG1 monoclonal antibody, 44-3A6, was raised against the human lung adenocarcinoma cell line, A549. It has been shown to react with a 40,000 MW protein found on the cell surface, which is preserved in formalin-fixed paraffin-embedded tissues. A recent study of pulmonary carcinomas utilizing immunohistochemical methods showed exclusive binding to lung adenocarcinomas, subsets of neuroendocrine tumors, some carcinoids and a subset of large cell carcinomas. Reactivity was not seen in squamous cell carcinomas and small cell neuroendocrine carcinomas. In addition, melanomas, sarcomas and hematologic malignancies do not express this antigen. We now report on the reactivity pattern of 44-3A6 in adenocarcinomas of nonpulmonary primary sites and in normal adults organs. Strong diffuse staining of neoplastic cells in adenocarcinomas of the stomach, colon, pancreas, gallbladder and breast was noted. Adenocarcinomas arising in the endometrium, ovary, kidney, prostate, thyroid and liver were either negative or showed weak and/or focal reactivity. Strong staining patterns were even noted in adenocarcinomas which had an 'undifferentiated' component; i.e., lacking well-defined glandular elements. Immunoreactivity was noted in epithelial cells in several tissues from which these adenocarcinomas arose including the bronchial tract, stomach, small intestine, pancreas and colon, whereas epithelial cells from the endometrium, kidney, ovary, prostate and thyroid were negative or showed diffuse weak immunoreactivity. Our finding indicate that monoclonal antibody 44-3A6 recognizes an epithelial antigen on subsets of normal as well as transformed glandular epithelia. The differential pattern of expression of its target antigen probably reflects differences in tumor genesis and/or differentiation.

This article describes a case of pleomorphic adenocarcinoma of the pancreas, metastatic to the adrenal glands and liver, that has unique cytological and histological features. Cytology demonstrated numerous mononuclear and multinucleated tumor giant cells as well as numerous osteoclast-like giant cells. These features were also seen in the histological sections, as were numerous clear cells. Electron microscopy demonstrated features suggesting an epithelial origin of the epulis cells. Prominent immunoreactivity with the monoclonal antibody (MCA) 44-3A6 of these cellular constituents was seen in the aspirate and in the tissue sections. These data provide further evidence to support the epithelial origin of these cellular components.