Assessment of urinary beta-core fragment of human chorionic gonadotropin as a new tumor marker of lung cancer.
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.
Yoshimura
M
M
Department of General Thoracic Surgery, Hyogo Medical Center for Adults, Japan.
Nishimura
R
R
Murotani
A
A
Miyamoto
Y
Y
Nakagawa
T
T
Hasegawa
K
K
Koizumi
T
T
Shii
K
K
Baba
S
S
Tsubota
N
N
D000230:Adenocarcinoma / Q000175:diagnosis; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000652:urine*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis; D006063:Chorionic Gonadotropin / Q000097:blood / Q000652:urine*; D018997:Chorionic Gonadotropin, beta Subunit, Human; D002850:Chromatography, Gel; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood / Q000652:urine*; D011869:Radioligand Assay
D014408:Biomarkers, Tumor; D006063:Chorionic Gonadotropin; D018997:Chorionic Gonadotropin, beta Subunit, Human; D010446:Peptide Fragments; C063554:urinary gonadotropin fragment