The immunohistochemical distribution and concentrations of tumor-antigen 4 (TA-4) in tissues and serum were determined in patients with benign and malignant diseases, including 27 patients with squamous cell carcinoma (SCC; 15 in the lung and 12 in the esophagus). Tumor-antigen 4 immunoreactivity was present in the cytoplasm of many SCC tissues, especially in the hyperparakeratotic region, and in the cytoplasm of differentiated squamous cells of the intermediate layer of normal epithelia of various organs, but not in those of other types of lung cancers or benign pulmonary diseases. Consistent with the results of immunostaining, the TA-4 concentrations in SCC tissues of the lung, esophagus, and normal squamous epithelia were much higher than in those of lung cancer other than SCC, benign pulmonary diseases, normal lung, and submandibular gland tissues. The TA-4 concentration in SCC tissue tended to increase with increasing grades of differentiation. Serum TA-4 was elevated in 15 of 27 patients with SCC but in no patients with other types of lung cancer or benign diseases. These results indicate that TA-4 is an antigen related to the differentiation of squamous cells and that tumor cells of SCC can release a large amount of TA-4 into circulation whereas normal squamous epithelia cannot.

Summary The serum level of tumour-antigen 4 (TA-4) was measured in 181 patients with squamous cell carcinoma (SCC) of various organs (71 lung, 24 uterus, 16 oesophagus, 64 head and neck and six skin), 34 patients with other types of lung cancer and 35 patients with benign diseases. To compare the results with those obtained by the conventional competitive radioimmunoassay (RIA) using a polyclonal antibody, a new immunoradiometric assay (IRMA) method was used which has recently been developed using two monoclonal antibodies raised to different epitopes of TA-4. Both methods provided essentially the same results: the serum TA-4 levels were high in patients with SCC of various organs when compared with those of healthy controls and patients with other types of lung cancer or benign diseases. However, the positive ratios assessed as the percentage of patients with elevated serum TA-4 levels were higher with the IRMA method than with the RIA method in SCC of all organs, as much as 2-3 times higher in SCC of the larynx, tongue and pharynx. In contrast, in patients with benign diseases or other types of lung cancer, there was no difference in the positive ratios between the two methods. This was largely due to the improvement in sensitivity and accuracy of assay with the new method, which resulted in a decrease in the normal value in healthy controls. It was concluded that with the new IRMA method using monoclonal antibodies, the diagnostic detectability of serum TA-4 is enhanced in SCC of all organs.Since the initial report of Kato and Torigoe (1977), it has been established that tumour-antigen 4 (TA-4), a protein fraction purified from squamous cell carcinoma (SCC) tissue of the uterine cervix, is a useful marker for uterine cervical SCC (Kato et al., 1979(Kato et al., , 1982(Kato et al., , 1983 Maruo et al., 1985). Previously, we measured serum TA-4 in patients with SCC of various organs including the lung, oesophagus, maxillary sinus and oral cavity and demonstrated that TA-4 is a useful marker for SCC not only of the uterine cervix but also of these organs, especially in evaluating therapeutic effects and monitoring recurrence (Mino et al., 1988). In the previous study, however, we also found that the serum TA-4 level and the positive ratio (the percentage of patients with serum TA-4 levels higher than the normal range) were not so high in the early stages of these diseases and even in the advanced stages in SCC of the tongue, larynx and pharynx, suggesting that its use in these cases was limited. This limitation may be due to, in part at least, the sensitivity and accuracy of the assay method used: the competitive conventional radioimmunoassay (RIA) method using a polyclonal antibody.Recently, monoclonal antibodies for TA-4 were obtained and an immunoradiometric sandwich assay (IRMA) method using two monoclonal antibodies was developed (Dainabot Co. Ltd, Tokyo, Japan) (Ikeda, 1987). Using the newly developed IRMA method, in the present study, we measured the serum TA-4 levels in healthy controls and in patients...