USA HCG REFERENCE SERVICE
DETAILED PROTOCOL

DESCRIPTION

The USA hCG Reference Service is a specialized consulting service. A referral includes the initial laboratory tests, specialized test as needed, and a careful review of the patient's history. Recommendations are then made regarding treatment and management. A formal clinical report is prepared for the patient's records by Laurence A. Cole PhD. The report is scrutinized and further comments made by Carolyn Muller MD, Gynecologic Oncologist.
The USA hCG Reference Service is certified by the Department of Heath and Human Services for running clinical tests for patient records (CLIA certification 32D0972561). The laboratory is monitored by the College of American Pathologists (CAP certification 7176750-01).
If you need to see our CLIA certification or print it click here. Printing requires Adobe Acrobat.

INITIAL LABORATORY TESTS

Initial tests are run to first show that the hCG result is real and not false positive, and then to initially differentiate potential diagnoses. The initial tests are-

1. Test total hCG in serum and in urine using the DPC Immulite automated hCG test on the Immulite platform. The DPC Immulite is chosen, because multiple blind trials with multiple centers throughout the world, show that this total hCG tests detects more hCG variants, on an equimolar basis, than any other commercial test (see list below and references). It also has no reported incidence of yielding a false positive hCG result. The DPC total hCG detects -
   regular hCG
   hyperglycosylated hCG
   nicked hCG
   nicked hCG missing ßCTP
   free ß-subunit
   hyperglycosylated free ß-subunit
   nicked free ß-subunit
   nicked free ß-subunit mising ßCTP
   hCG ß-subunit core fragment

   1a. test unidluted serum
   1b. test 1/2 diluted serum
   1c. test 1/10 diluted serum (if possible)
   1e. test undiluted urine
   1f. test undiluted serum treated with Scantibodies HBR heterophilic antibody blocking agent

Cole, L.A., Shahabi, S., Butler, S., Mitchell, H., Newlands, E.S., Behrman, H.R., Verrill, H.L. Utility of commonly used commercial hCG immunoassays in the diagnosis and management of trophoblastic diseases. Clin Chem 47:308-315, 2001.

Cole LA ,Sutton JM, Higgins TN. Higgins, Cembrowski GS. Between-Method Variation in hCG Test Results, Clin Chem, 50:874-882, 2004.

2. Test hCG free ß-subunit, DPC Immulite automated hCG free ß-subunit test, in serum and urine. A high proportion of free ß-subunit in serum and urine is indicative of placental site trophoblastic tumor (PSTT) or non-trophoblastic malignancy.

Cole LA, Khanlian SA, Muller CY, Giddings A, Kohorn EI, Berkowitz R. Gestational trophoblastic diseases: 3 . Human Chorionic Gonadotropin Free ß-subunit a Reliable Marker of Placental Site Trophoblastic Tumors. Gyn Oncol, in press 2006.

3. Test hyperglycosylated hCG in serum and urine. This is the Nichols Advantage hyperglycosylated hCG test. This is performed on the Nichols Advantage automated platform. The presence of hyperglycosylated hCG marks the presence of active or invasive cytotrophoblast cells. Measurement of hyperglycosylated hCG can differentiate active and inactive (quiescent GTD) trophoblast disease as well as the presence of recurrent trophoblastic disease prior to rising hCG levels or the appearance of tumor.

Cole LA, Dai D, Leslie KK, Butler SA, Kohorn EI. Gestational trophoblastic diseases: 1. Pathophysiology of hyperglycosylated hCG-regulated neoplasia. Gynecologic Oncology, in press, 2006

Cole LA, Dai D, Leslie KK, Butler SA, Kohorn EI. Gestational trophoblastic diseases: 2. Hyperglycosylated hCG as a Reliable Marker of Active Neoplasia. Gynecologic Oncology, in press, 2006

SPECIALIZED LABORATORY TESTS

a. Intact hCG only (microtiter plate test), this test detects only whole hCG dimer

b. Hyperglycosylated hCG confirm (microtiter plate test), an equilibrium incubation test to confirm the presence of hyperglycosylated hCG

c. hCG free ß-subunit confirm (microtiterplate) to confirm the presence of free ß-subunit

d. hCG ß-core fragment test (microtiter plate test), to detect the urinary breakdown product of hCG free ß-subunit

e. Nicked hCG test (microtiter plate test) to detect presence of nicked or degraded hCG

f. Luteinizing hormone (LH) test on DPC Immulite automated platform. To investigate a pituitary source of hCG

INDICATORS

1. False positive hCG
a. Persistent low levels of hCG, <1000 mIU/ml
b. hCG in serum but not urine
c. serum hCG blocked by HBR heterophilic antibody blocking agent
d. Widely varying hCG result in multiple hCG tests

2. Active invasive gestational trophoblastic disease, Choriocarcinoma and GTN
a. Presence of hyperglycosylated hCG

3. Quiescent (inactive) gestational trophoblastic disease
a. Persistent low levels of hCG, <200 mIU/ml
b. Absence of hyperglycosylated hCG

4. Active testicular germ cell malignancies
a. Presence of hyperglycosylated hCG

5. PSTT (Placental site trophoblastic tumor)
a. Presence of major proportion of hCG due to hCG free ß-subunit
b. Presence of major proportion of hCG due to hCG ß-core fragment in urine

6. Ovarian germ cell and other non-trophoblastic hCG-producing
malignancies
a. Presence of >80% of hCG due to hCG free ß-subunit
b. Presence of >80% of hCG due to hCG ß-core fragment in urine

7. Pituitary origin hCG in peri- or post-menopausal women
a. Persistent low levels of regular hCG <25 mIU/ml
b. Women peri- and postmenopause women, or during ovulation

8. Ectopic pregnancy or spontaneously-aborting pregnancy
a. Presence of regular hCG
b. Absence of significant hyperglycosylated hCG

Laurence A. Cole PhD
The Howard & Friedman Distinguished Professor of Obstetrics & Gynecology.
Director, USA hCG Reference Service
Professor and Chief, Women's Health Research
University of New Mexico
Secretary, International Society for Study of Trophoblastic Diseases

Dr. Laurence Cole is expert on hCG tests and on Gestational Trophoblastic Diseases with over 200 first author publications about these fields.

Carolyn Y. Muller MD
Professor and Chief, Division of Gynecologic Oncology
Department of Obstetrics and Gynecology
University of New Mexico

Dr. Carolyn Muller is a board certified Gynecologic Oncologist and expert in the treatment and management of all woman's reproductive tract malignancies. She directs the Gynecologic Oncology expert group at University of New Mexico.

Sarah A. Khanlian MPH
Laboratory Director, USA hCG Reference Service
University of New Mexico

Sarah Khanlian is an hCG test specialist. She has been organizing, performing, managing, and teaching others how to perform and set-up hCG and hCG-related molecule tests for over 5 years. This includes all types of tests ranging from automated and manual tests with old and new technologies, to POC and OTC tests, to designing special tests for unique situations.

Links to other pages on the USA hCG Reference Service Website

A. hCG Reference Service HOME PAGE

B. hyperglycosylated hCG

C. pituitary hCG

D. synthesis

E. heterophilic antibodies

F. For further information on Gestational Trophoblastic Disease (GTD) and on the worlds GTD experts

G. For the USA hCG Reference Service detailed protocol

1. False positive hCG

2. Active invasive gestational trophoblastic disease, Choriocarcinoma and GTN

3. Quiescent (inactive) gestational trophoblastic disease

4. Active testicular germ cell malignancies

5. PSTT (Placental site trophoblastic tumor)

6. Ovarian germ cell and other non-trophoblastic hCG-producing
malignancies

7. Pituitary origin hCG in peri- or post-menopausal women

8. Ectopic pregnancy or spontaneously-aborting pregnancy


USA HCG REFERENCE SERVICE DETAILED PROTOCOL DESCRIPTION The USA hCG Reference Service is a specialized consulting service. A referral includes the initial laboratory tests, specialized test as needed, and a careful review of the patient's history. Recommendations are then made regarding treatment and management. A formal clinical report is prepared for the patient's records by Laurence A. Cole PhD. The report is scrutinized and further comments made by Carolyn Muller MD, Gynecologic Oncologist. The USA hCG Reference Service is certified by the Department of Heath and Human Services for running clinical tests for patient records (CLIA certification 32D0972561). The laboratory is monitored by the College of American Pathologists (CAP certification 7176750-01). If you need to see our CLIA certification or print it click here. Printing requires Adobe Acrobat. INITIAL LABORATORY TESTS Initial tests are run to first show that the hCG result is real and not false positive, and then to initially differentiate potential diagnoses. The initial tests are- 1. Test total hCG in serum and in urine using the DPC Immulite automated hCG test on the Immulite platform. The DPC Immulite is chosen, because multiple blind trials with multiple centers throughout the world, show that this total hCG tests detects more hCG variants, on an equimolar basis, than any other commercial test (see list below and references). It also has no reported incidence of yielding a false positive hCG result. The DPC total hCG detects - regular hCG hyperglycosylated hCG nicked hCG nicked hCG missing ßCTP free ß-subunit hyperglycosylated free ß-subunit nicked free ß-subunit nicked free ß-subunit mising ßCTP hCG ß-subunit core fragment 1a. test unidluted serum 1b. test 1/2 diluted serum 1c. test 1/10 diluted serum (if possible) 1e. test undiluted urine 1f. test undiluted serum treated with Scantibodies HBR heterophilic antibody blocking agent Cole, L.A., Shahabi, S., Butler, S., Mitchell, H., Newlands, E.S., Behrman, H.R., Verrill, H.L. Utility of commonly used commercial hCG immunoassays in the diagnosis and management of trophoblastic diseases. Clin Chem 47:308-315, 2001. Cole LA ,Sutton JM, Higgins TN. Higgins, Cembrowski GS. Between-Method Variation in hCG Test Results, Clin Chem, 50:874-882, 2004. 2. Test hCG free ß-subunit, DPC Immulite automated hCG free ß-subunit test, in serum and urine. A high proportion of free ß-subunit in serum and urine is indicative of placental site trophoblastic tumor (PSTT) or non-trophoblastic malignancy. Cole LA, Khanlian SA, Muller CY, Giddings A, Kohorn EI, Berkowitz R. Gestational trophoblastic diseases: 3 . Human Chorionic Gonadotropin Free ß-subunit a Reliable Marker of Placental Site Trophoblastic Tumors. Gyn Oncol, in press 2006. 3. Test hyperglycosylated hCG in serum and urine. This is the Nichols Advantage hyperglycosylated hCG test. This is performed on the Nichols Advantage automated platform. The presence of hyperglycosylated hCG marks the presence of active or invasive cytotrophoblast cells. Measurement of hyperglycosylated hCG can differentiate active and inactive (quiescent GTD) trophoblast disease as well as the presence of recurrent trophoblastic disease prior to rising hCG levels or the appearance of tumor. Cole LA, Dai D, Leslie KK, Butler SA, Kohorn EI. Gestational trophoblastic diseases: 1. Pathophysiology of hyperglycosylated hCG-regulated neoplasia. Gynecologic Oncology, in press, 2006 Cole LA, Dai D, Leslie KK, Butler SA, Kohorn EI. Gestational trophoblastic diseases: 2. Hyperglycosylated hCG as a Reliable Marker of Active Neoplasia. Gynecologic Oncology, in press, 2006 SPECIALIZED LABORATORY TESTS a. Intact hCG only (microtiter plate test), this test detects only whole hCG dimer b. Hyperglycosylated hCG confirm (microtiter plate test), an equilibrium incubation test to confirm the presence of hyperglycosylated hCG c. hCG free ß-subunit confirm (microtiterplate) to confirm the presence of free ß-subunit d. hCG ß-core fragment test (microtiter plate test), to detect the urinary breakdown product of hCG free ß-subunit e. Nicked hCG test (microtiter plate test) to detect presence of nicked or degraded hCG f. Luteinizing hormone (LH) test on DPC Immulite automated platform. To investigate a pituitary source of hCG INDICATORS 1. False positive hCG a. Persistent low levels of hCG, <1000 mIU/ml b. hCG in serum but not urine c. serum hCG blocked by HBR heterophilic antibody blocking agent d. Widely varying hCG result in multiple hCG tests 2. Active invasive gestational trophoblastic disease, Choriocarcinoma and GTN a. Presence of hyperglycosylated hCG 3. Quiescent (inactive) gestational trophoblastic disease a. Persistent low levels of hCG, <200 mIU/ml b. Absence of hyperglycosylated hCG 4. Active testicular germ cell malignancies a. Presence of hyperglycosylated hCG 5. PSTT (Placental site trophoblastic tumor) a. Presence of major proportion of hCG due to hCG free ß-subunit b. Presence of major proportion of hCG due to hCG ß-core fragment in urine 6. Ovarian germ cell and other non-trophoblastic hCG-producing malignancies a. Presence of >80% of hCG due to hCG free ß-subunit b. Presence of >80% of hCG due to hCG ß-core fragment in urine 7. Pituitary origin hCG in peri- or post-menopausal women a. Persistent low levels of regular hCG <25 mIU/ml b. Women peri- and postmenopause women, or during ovulation 8. Ectopic pregnancy or spontaneously-aborting pregnancy a. Presence of regular hCG b. Absence of significant hyperglycosylated hCG Laurence A. Cole PhD The Howard & Friedman Distinguished Professor of Obstetrics & Gynecology. Director, USA hCG Reference Service Professor and Chief, Women's Health Research University of New Mexico Secretary, International Society for Study of Trophoblastic Diseases Dr. Laurence Cole is expert on hCG tests and on Gestational Trophoblastic Diseases with over 200 first author publications about these fields. Carolyn Y. Muller MD Professor and Chief, Division of Gynecologic Oncology Department of Obstetrics and Gynecology University of New Mexico Dr. Carolyn Muller is a board certified Gynecologic Oncologist and expert in the treatment and management of all woman's reproductive tract malignancies. She directs the Gynecologic Oncology expert group at University of New Mexico. Sarah A. Khanlian MPH Laboratory Director, USA hCG Reference Service University of New Mexico Sarah Khanlian is an hCG test specialist. She has been organizing, performing, managing, and teaching others how to perform and set-up hCG and hCG-related molecule tests for over 5 years. This includes all types of tests ranging from automated and manual tests with old and new technologies, to POC and OTC tests, to designing special tests for unique situations. Links to other pages on the USA hCG Reference Service Website A. hCG Reference Service HOME PAGE B. hyperglycosylated hCG C. pituitary hCG D. synthesis E. heterophilic antibodies F. For further information on Gestational Trophoblastic Disease (GTD) and on the worlds GTD experts G. For the USA hCG Reference Service detailed protocol 1. False positive hCG 2. Active invasive gestational trophoblastic disease, Choriocarcinoma and GTN 3. Quiescent (inactive) gestational trophoblastic disease 4. Active testicular germ cell malignancies 5. PSTT (Placental site trophoblastic tumor) 6. Ovarian germ cell and other non-trophoblastic hCG-producing malignancies 7. Pituitary origin hCG in peri- or post-menopausal women 8. Ectopic pregnancy or spontaneously-aborting pregnancy
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USA HCG REFERENCE SERVICE DETAILED PROTOCOL

USA HCG REFERENCE SERVICE
DETAILED PROTOCOL