American Association for Clinical Chemistry
Better health through laboratory medicine
Laurence Cole, PhD
2000 Sigi Ziering Award for Outstanding Contribution for a Publication in the Journal Clinical Chemistry

Laurence Cole, PhD, will receive the first publication award, sponsored by Diagnostics Products Corporation (DPC). Laurence Cole was born in the United Kingdom and came to the United States in 1977. He obtained a PhD in Biochemistry in 1982 at the Medical College of Wisconsin, in Milwaukee. His mentor, Robert Hussa, PhD, was working on the structure and synthesis of the hormone human chorionic gonadotropin (hCG) in cancer cells. Laurence Cole was studying in the laboratories of Roland Pattillo, MD, in the Department of Obstetrics and Gynecology, whose principal interest was trophoblastic diseases and the establishment and testing of choriocarcinoma cell lines (Jar, BeWo, JEG3, and others). It was this environment that set Laurence Cole into a lifetime dedicated to the physiology, immunochemistry, and biochemistry of hCG, and to the study of trophoblastic diseases.

In 1982, Dr. Cole started working on a postdoctoral fellowship in the field of hCG and cancer and hCG and trophoblastic diseases in the Department of Pharmacology at University of Michigan in Ann Arbor, Michigan. In 1985, he moved to Yale University. For 14 years, Dr. Cole led a laboratory specializing in hCG biochemistry and immunoassay, conducting basic structural and physiological experiments and translation studies evaluating clinical applications. For most of the period, Dr. Cole was principal investigator on two consecutive National Institutes of Health grants. In response to demand, in January 1998 Dr. Cole started the USA hCG Reference Service, a consulting service running specialized hCG/hCG-related molecule tests, aiding physicians and clinical laboratories with interpretation of confusing commercial hCG assay results. In October 1999, Dr. Cole, his laboratory, and the hCG Reference Service moved to Albuquerque, New Mexico. Dr. Cole currently is Professor of Obstetrics and Gynecology, and of Biochemistry and Molecular Biology at the University of New Mexico, and Chief of the new Division of Women’s Health Research. His newest challenge is the expansion of a new women’s health research facility with a hallway of laboratories.

Dr. Cole has personally written (as first author or senior author) more than 100 articles on hCG structure, physiology, and immunoassay or on clinical applications of hCG or hCG-related molecules. He also has four active hCG-related patents. Dr. Cole’s early research included the original demonstration of the free ß-subunit of hCG in pregnancy serum (Cole et al., Endocrinology 1983;113:1176–8). hCG free ß-subunit is measured in serum today as a marker of Down syndrome. His early research also included the initial demonstration that free ß-subunit and ß-core fragment were useful as tumor markers in following cervical and other gynecological cancers (Cole et al., Cancer Res 1988;48:1356–60). Urinary ß-core fragment is now used, particularly in Japan, as a marker for managing advanced cervical cancer. Dr. Cole’s other research includes the first identification of abnormal O-linked sugar side chains on hCG produced by cancer cells (Cole LA. J Clin Endocrinol Metab 1987;65:811–3). A specific hCG assay that measures hCG with abnormal O-linked sugar side chains is used by the USA hCG Reference Service in identifying hCG of cancer origin.

In the 1990s, Dr. Cole’s team examined the structures of the various degradation products of hCG in serum and urine in normal pregnancy, abnormal pregnancy, and trophoblastic diseases. Specific degradation pathways were identified for hCG (Cole et al. J Clin Endocrinol Metab 1993;76:704–10); Dr. Cole’s team also studied the recognition, or lack of recognition of the different forms of hCG by various commercial hCG/hCGß immunoassays (Cole LA. Clin Chem 1997;43:2233–43). Other important works by Dr. Cole include the establishment of the complete peptide and N- and O-linked carbohydrate structures of hCG and its subunits from normal and abnormal pregnancies and trophoblastic diseases (Elliott et al. Endocr J 1977;7:15–32).

Dr. Cole’s recent work includes the identification of a unique hCG variant, hyperglycosylated hCG, in pregnancies with a Down syndrome fetus. Multiple translational studies were carried out. These showed that this single test can detect 80% of Down syndrome pregnancies (at a 5% false-positive rate) and that this test combined with other markers can detect >90% of Down syndrome cases at a 3% false-positive rate. The efficiency of this test and the combination of this test and others surpasses any previous marker or markers. This test currently is undergoing clinical evaluation for screening for Down syndrome in the state of California (Cole et al. Clin Chem 1999;45:2109–19). Other recent publications include the observation by the USA hCG Reference Service of 12 women with false-positive hCG test results. Seven of the 12 women underwent therapy, chemotherapy, hysterectomy, or other major surgery because of a false diagnosis of choriocarcinoma, based solely on multiple false-positive hCG results (Rotmensch and Cole. Lancet 2000;355:712–5).

Dr. Cole continues to carry out grant-funded research based around hCG. Currently, he is examining the structure of hCG in hyperemesis gravidarum in pregnancy and evaluating screening tests for preeclampsia. The team is also investigating the role of hCG in malignancy or invasion by trophoblastic cells.

Dr. Cole's award winning article is entitled:

“Hyperglycosylated Human Chorionic Gonadotropin (Invasive Trophoblastic Antigen) Immunoassay: A New Basis for Gestational Down Syndrome Screening.” Co-authors were S. Shahabi, U.A. Oz, R.O. Bahado-Singh, and M.J. Mahoney,

1999 Dec;45(12):2109-19.

Dr. Cole'saward winning article can be read in its entirety