Assessment of urinary beta-core fragment of human chorionic gonadotropin as a new tumor marker of lung cancer

Cancer. 1994 Jun 1;73(11):2745-52. doi: 10.1002/1097-0142(19940601)73:11<2745::aid-cncr2820731116>3.0.co;2-v.

Abstract

Background: Some patients with lung cancer have been found to have elevated levels of serum immunoreactive human chorionic gonadotropin (hCG)/hCG beta (IR-beta), but it is uncertain whether it would be valuable as a tumor marker. Recently, IR-beta has been demonstrated to consist of at least three different molecules, intact hCG, free hCG beta, and hCG beta-core fragment (beta-CF), in body fluids. In this study, the authors qualitatively analyzed IR-beta 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 hCG beta, and beta-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-beta in the urine, although only 12 had elevated values of IR-beta in the serum. The greater part of the elevated urinary IR-beta was identified to be beta-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 beta-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 beta-CF between two major types of lung cancer: adenocarcinoma (49.2%) and SCC (45.2%). Immunohistochemical study revealed positive staining of IR-beta in the cancer tissues from 5 of 12 patients with elevated levels of IR-beta, in which most of the positive cases had the elevated levels of serum free hCG beta (> 0.5 ng/ml) and/or urinary beta-CF (> 1.0 ng/mg of creatinine).

Conclusions: Ectopic production of IR-beta by lung cancer is not rare, and urinary beta-CF might be a potential tumor marker of lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / diagnosis
  • Adult
  • Aged
  • Biomarkers, Tumor / urine*
  • Carcinoma, Squamous Cell / diagnosis
  • Chorionic Gonadotropin / blood
  • Chorionic Gonadotropin / urine*
  • Chorionic Gonadotropin, beta Subunit, Human
  • Chromatography, Gel
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Immunohistochemistry
  • Lung Neoplasms / diagnosis*
  • Male
  • Middle Aged
  • Peptide Fragments / blood
  • Peptide Fragments / urine*
  • Radioligand Assay

Substances

  • Biomarkers, Tumor
  • Chorionic Gonadotropin
  • Chorionic Gonadotropin, beta Subunit, Human
  • Peptide Fragments
  • urinary gonadotropin fragment