Tissue polypeptide specific antigen (TPS) and objective response to treatment in solid tumors

CR =comp! ete response or post-surgical disease-free status; PR=partial remission; MR = minor regression; NC = no change: PD = progressive discase TABLE 1PERCENTAGE OF ELEVATED VALUES (HIGHER THAN 40 U/L) AND MEAN LEVELS OF TPS IN PATIENTS GROUPED ACCORDING TO TREATMENT RESPONSE In order to find a means of correlating proliferation rates with the state of tumor activity (growth), the new concept of clinical objectivity criteria was introduced. Patients were divided into three categories: STABLE, SLOW, and RAPID. In particular, CR and PR were defined as stable disease (STABLE); MR and NC (No Change) were merged into the slow disease category (SLOW) and progressive disease was allocated to the rapid disease category (RAPID). TPS measurements were performed on stored serum samples using a commercial Kit (BEKI Diagnostic, Bromma, Sweden) according to the manufacturer's instructions. The reference value of TPS for our laboratory was 35 U/L. As preliminary statistical analysis revealed that the distribution ofTPS values was not Gaussian, we adopted only non-parametric tests. The Kruskall-Wallis analysis of variance, the Mann-Whitney U-test or the Kendall rank correlation were used as appropriate, A total of 154 serum assays were evaluated. One hundred and seven were performed to evaluate objective response to treatment; forty seven were performed in healthy control subjects, Median TPS values were significantly higher (p=O.OOOI) in patients (69 U/L) than in controls (20 U/L). Sixty-two patients (57,9%) had TPS levels exceeding 35 U/L (95th percentile of the healthy subjects) (Tab, I), TPS varied considerably in patients with different objective responses to treatment (Tab. I). In particular, higher values were asDear Sir, In recent years several tumor products, including hormones, fetal proteins, and enzymes have been used as biological markers in the follow-up of patients with cancer. Among the numerous biological markers available, tissue polypeptide antigen (TPA) was used as a prognostic parameter in lung cancer and in other solid tumors (1-3), TPA was first isolated from various types of human cancers by Bjorklund (4). It is a chemically well-defined substance produced and released by proliferating cells (5). Clinical investigations have established that the level of TPA is a useful indicator of the proliferative activity of cancer cells (6,7). Extensive monoclonal mapping of TPA (8,9) revealed that it contained 35 different epitopes, only two of which are essential for the original TPA specificity as related to proliferative activity and common human tumor antigenicity (the pertinent activity is related to one epitope, tissue polypeptide specific antigen (TPS), in an arrayal' more than 30 others). The corresponding monoclonal antibody, M3, is used in the present assay. In our study we have assayed serum levels ofTPS in 107 patients with various solid tumors and in 47 healthy subjects in order to define the correlation of TPS with the objective response in treated patients. One hundred and seven patients, (79% males, median age 66 years, range 32-87), 27 with small cell lung cancer, 37 with non-small cell lung cancer (most sq uamous cell carcinoma), 21 with breast adenocarcinoma, 12 with colorcctal carcinoma, 4 with pancreas or gastric adenocarcinoma and 6 with other solid tumors, were assayed for TPS during the evaluation of the objective response to treatment. All patients were treated with chemotherapy, radiotherapy, hormone therapy or supportive care, as appropriate. Standard criteria for objective response were used, Minor regression (MR) was defined as any unequivocal tumor volume reduction which did not fulfill the criteria of at least partial remission (PR). Surgical patients were allotted to complete response (CR) or PR categories in the case of complete or partial resection, respectively. STABLE (CR. PRJ SLOW (NC. MR) RAPID (PD) N.ofpts % X SD