Assessment of urinary β‐core fragment of human chorionic gonadotropin as a new tumor marker of lung cancer

Abstract

Background. Some patients with lung cancer have been found to have elevated levels of serum immunore‐active human chorionic gonadotropin (hCG)/hCGß (IR‐β), but it is uncertain whether it would be valuable as a tumor marker. Recently, IR‐β has been demonstrated to consist of at least three different molecules, intact hCG, free hCGβ, and hCGβ‐core fragment (β‐CF), in body fluids. In this study, the authors qualitatively analyzed IR‐β in the serum and urine of patients with lung cancer and assessed its clinical usefulness as a tumor marker. Methods. Highly sensitive and specific enzyme immunoassays were established to measure intact hCG, free hCGβ, and β‐CF in the serum and urine of patients with lung cancer. Results. Of 99 patients with lung cancer, almost half of the patients achieved positive values of IR‐β in the urine, although only 12 had elevated values of IR‐β in the serum. The greater part of the elevated urinary IR‐β was identified to be β‐CF by gel chromatography on Sephadex G‐100 (Pharmacia LKB Biotechnology, Tokyo, Japan), leading the authors to assess its usefulness as a tumor marker for lung cancer. Based on the cutoff value (0.2 ng/mg of creatinine) from healthy subjects, the overall positive rate of urinary β‐CF for lung cancer was 48.5% (48 of 99 patients). The incidence of the marker increased with stage of disease, from 35.7% (15 of 42) in Stage I and 35.7% (5 of 14) in Stage II to 62.5% (20 of 32) in Stage III and 72.7% (8 of 11) in Stage IV. These positive rates exceeded or equaled those of the serum tumor markers, carcinoembryonic antigen, and squamous cell carcinoma (SCC)‐related antigen, measured simultaneously in the same patients. The author were encouraged that there was no significant difference in the positive rates of urinary β‐CF between two major types of lung cancer: adenocarcinoma (49.2%) and SCC (45.2%). Immunohistochemical study revealed positive staining of IR‐β in the cancer tissues from 5 of 12 patients with elevated levels of IR‐β, in which most of the positive cases had the elevated levels of serum free hCGβ (>0.5 ng/ml) and/or urinary β‐CF (>1.0 ng/mg of creatinine). Conclusions. Ectopic production of IR‐β by lung cancer is not rare, and urinary β‐CF might be a potential tumor marker of lung cancer. Cancer 1994; 73:2745–52. Copyright © 1994 American Cancer Society