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CC/NUMBER 43
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Week’s Citation classic
Brannatein G D, Vahukaith I L, Casbone p p & Ross C T. Ectopic production of
human chorionic gonadotrophin by neoplasins. Ann. Intern. Med. 78:39-45, 1973.
(Reproduction Research Branch, Nat!. Inst. Child Health and Human Development,
and Clinical Oncology Area, Nat!. Cancer Inst., Nat!. mats. Health, Bethesda, MD)
Using a sensitive and specific radioimmunoassay
to measure serum concentrations of human chorionic gonadotrophin (hCG), 59 percent of patients
with testicular tumors and over seven percent of
patients with a wide variety of non-testicular
cancers were found to5have immunoreactive hCC
in their sera. [The Sd indicates that this paper
has been cited in over 330 publications since
1973.)
was proved correct when we found that the
antibodies raised against the beta subunit of
hCG had relatively little cross-reactivity
with ISLH. We immediately recognized the
potential clinical application of a radioimmunoassay using these antibodies for
diagnosis of early pregnancy and for monitoring the therapy of gestational trophoblastic disease. Our paper describing this radioimmunoassay (beta hCG RIA) has recently
2
been featured as a Citation Classic.’.
“In initiating our clinical studies of hCG
measurements with this assay, we found that
we had numerous blood samples from womGlenn D. Braunstein
en with gestational trophoblastic disease,
Department of Medicine
but relatively few samples from men with
Cedars-Sinai Medical Center
trophoblastic testicular tumors. We learned
University of California School of Medicine that Paul Carbone of the National Cancer InLos Angeles, CA 90048
stitute had established a tumor serum bank
which contained blood samples obtained
from patients with testicular tumors. The
June 1, 1983 serum bank contained hundreds of samples
from patients with a wide variety of malig“In 1970, I had the good fortune of joining nancies as well as some samples from paGruff Ross in his laboratory at the National tients with non-neoplastic disorders. We
Institutes of Health. Griff had received measured the immunoreactive hCG in the
highly purified preparations of human chori- sera from 918 patients with cancer and 443
onic gonadotrophin (hCG) and its alpha and control patients and found that 59 percent
beta subunits prepared by Robert Canfield of the patients with testicular tumors and
at Columbia University College of Physi- 7.~
percent of the patients with non-trophocians & Surgeons. Griff and Judy Vaitukaitis blastic neoplasms had immunoreactive hCG
immunized a number of rabbits with these in their circulation while only 0.7 percent of
materials in order to develop antisera that the control patients had detectable hCG. Pawould be useful in defining the immunolog- tients with carcinomas of the stomach, liver,
ic characteristics of hCG and the other gly- pancreas, and breast, and with myeloma and
coprotein hormones. It was known that the melanoma had the highest frequency of posintact hCG molecule shared some structural itive responses. This was a higher frequency
characteristics with human thyroid stimulat- of hCG production by non-trophoblastic
ing hormone, follicle stimulating hormone, cancers than had been previously recogand especially lutelnizing hormone (hLH). nized.
Indeed, the biologic and immunologic ac“I feel that this study became a Citation
tivity of native IICG and hLH were so similar Classic because it was one of the first systhat only elaborate chromatographic or tematic investigations of ectopic production
electrophoretic methods were capable of of a hormone by tumors. The unexpectedly
separating these two hormones.
high frequency of hCG production by non“Griff had predicted that antibodies gen. trophoblastic cancers stimulated a number
orated against the purified subunits of hCG of laboratories to study the ectopic produc3
might have a greater affinity for intact hCG
tion of hCG and other hormones bytumers.
than hLH, and therefore would allow the de- Furthermore, our study suggested that horvelopment of a radioimmunoassay that mones may be useful as objective markers
cou!d be used to distinguish serum levels of for the diagnosis of cancer and for monitorhCG from circulating hLH. His prediction ing the effects of therapy.”
1. Ve1t.kak~JL. &ante~ G D a Rois G T. A rsdioimmunoassay which specilicafly measures human chononic
gonadot opin in the presence of human luteinlzlng hormone. Amer. I. Obstet. Gyn.ecoL 113:751-8. 1972.
2. VabüaltI IL, Citation Classic. Commcntaiy on Amer I. Obstet. GynecoL 113:751-8, 1972.
Current Contenul ClinIcal Practice 1l(I0):24, 7 March 1983.
3.~BiauasteM G D. hCG expression introphoblastic and non.uophoblastic tumors. (Fislsmats W H, ad.)
Oncodevelopmenioi mar*err: biologic, diabetic and monitonng aspectt, polum. II.
New York: Academic Press. In press, 1983.
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