AbstractThis article reviews the recent studies reporting the applications of immunocytochemistry to diagnostic problems in clinical cytology. A series of studies with monoclonal antibody (MAb) B72.3 is discussed in detail. MA6 B72.3, reactive with a high molecular weight, glycoprotein, tumor-Associated antigen, designated TAG-72, has been shown previously to be reactive with formalin-fixed, parafin-embedded tissue sections of adenocarcinomas of the ovary, colon, and breast, but not a variety of normal adult tissues. It has demonstrated utility as an immunocytochemical adjunct to diagnose carcinoma in cell block and cytocentrifuge preparations of human serous effusions, with selective reactivity for tumor cells (particularly adenocarcinomu) over reactive mesothelium. Using the avidin-biotin complex (ABC) method of immuno-peroxidase staining and formalin-fixed, paraffin-embedded cell suspensions, MAb B72.3 detected tumor cells in effusions from the majority of patients with adenocarcinoma of the breast. No reactivity was demonstrated in any cell type in benign effisions. In conrrast, MAb 872.3 showed no reactivity to leukemic or lymphomutous effusions, or to mesothelial cells from malignant effusions. MAb B72.3 also detected tumor cells in emion specimens from most of the patients with“non-small cell”carcinoma of the lung and with carcinoma of the ovary. MA6 B72.3 was also used with fine-needle aspiration biopsies (FNABs) and corresponding surgically excised tumors to determine cellular reactivity. Positive staining with MA6 B72.3 was observed in needle aspirates of the great majority of“non-small cell”carcinomas of the lung, adenocarcinomas of the breast, adenocarcinomas of the colon, and carcinomas from other body sites. In contrast, small cell carcinomas of the lung, malignant melanomas, lymphomas, sarcomas, and glial tumors stained negatively with the antibody. Most benign lesions from the breast, lung, pancreas, parotid, and thyroid also showed no staining. In many patients, tumor-bearing tissue had also been resected and was available for comparative examination with MAb 8723. In more than 90% of these patients, the staining patterns of tumor cells in the aspirates were found to be predictive of the patterns of antibody reactivity in the comparable surgically resected tumors. From these studies it is concluded that MAb B72.3 defines a tumor-Associated antigen that is expressed in neoplastic cells versus benign cells, is most selectively expressed in carcinomas, and may be used as a novel adjunct for the diagnosis of neoplasms in effusions and in FNABs.