MINISTRY OF EDUCATION MINISTRY OF HEALTH
HANOI MEDICAL UNIVERSITY
PHAM THI DIEU HA
RESEARCH ON THE VALUE OF TUMOR
MARKER CA125 AND HE4 IN DIAGNOSIS
STAGE AND TREATMENT OVARIAN CANCER
Specialization: Oncology
Code: 62720149
SUMMARY OF MEDICAL DOCTORAL THESIS
HA NOI – 2021
The study was completed at:
HANOI MEDICAL UNIVERSITY
The scientific instructor:
Assoc. Prof. Dr. Nguyen Van Tuyen
Assoc. Prof. Dr. Nguyen Thi Ha
Reviewer 1:
Reviewer 2:
Reviewer 3:
The dissertation will be defended in front of the University
Thesis Evaluation CouncilMeeting at: Hanoi Medical University
At: day 2021
Thesis can be learned at library
1. The National Library
2. Library of Hanoi Medical University
LIST OF PUBLISHED ARTICLES RELATED TO THE STUDY
1. Pham Thi Dieu Ha (2019). Comment on values of CA125,
HE4 and Test ROMA in monitoring ovarian cancer treatment.
Vietnam Journal of Oncology, No. 2, 2019, 403-410.
2. Pham Thi Dieu Ha, Nguyen Van Tuyen (2020). Comment on
CA125, HE4 values in recurrent ovarian cancer. Journal of
Vietnamese Medicine, April 2, 2020, 205-208.
1
INTRODUCTION
Ovarian cancer is the leading cause of death in gynecological cancers
and ranks seventh in cancer in general in women. In Vietnam, in
2020, the number of new cases of ovarian cancer is 1 404 cases and
923 deaths. This is a burden of disease for individuals and society
because the disease is difficult to prevent, difficult to diagnose at an
early stage, and difficult to monitor for early detection of recurrence
to decide on early treatment.
Tumor markers CA125 (carcinoma antigen 125) and HE4 (human
epididymal protein 4) are used in ovarian cancer to help diagnose,
monitor treatment and monitor recurrence. The CA125 tumor marker
has high sensitivity but low specificity, while HE4 is the opposite.
The tumor marker HE4 is slightly increased in benign ovarian
tumors, with high specificity in ovarian cancer. In the past decade,
HE4 has emerged as an additional tumor marker for CA125,
promising to solve the inadequacies in ovarian cancer, early
diagnosis and early recurrence monitoring. The ROMA test
regression algorithm is an algorithm that combines two markers
CA125 and HE4 to increase the sensitivity and specificity in the
diagnosis and monitoring of ovarian cancer treatment. In Vietnam
and around the world, the CA125, HE4, ROMA test is applied in the
diagnosis of ovarian cancer, but there is no research using the
CA125, HE4, ROMA test to assess and monitor the response in the
treatment of ovarian cancer, in order to increase efficiency in
diagnosis, monitoring and management of ovarian cancer
CA125 and HE4 tumor markers have been applied at K hospital in
the diagnosis and monitoring of ovarian cancer, so the topic: "Study
on the value of CA125 and HE4 tumor markers in stage diagnosis.
Ovarian cancer staging and follow-up" was conducted with 2
objectives:
1. Understanding the correlation between tumor markers CA125 and
HE4 in ovarian cancer diagnosis.
2. Evaluation of the role of tumor markers CA125 and HE4 in
monitoring and treating ovarian cancer.
NEW CONTRIBUTIONS OF THE THESIS
This is the first study in Vietnam with a large enough sample
2
size to evaluate the role of tumor markers CA125, HE4 and ROMA
test algorithm in the diagnosis and monitoring of ovarian cancer.
Research results show that:
- The concentration of CA125, HE4, ROMA increased gradually
according to the disease stage, the later the disease stage, the higher
the concentration of CA125, HE4, ROMA, the mean concentration of
serum CA125: 1259,9±1551,96 U/ml, HE4: 634,1±578,45 pmol/l,
ROMA test: 89,7±14,0%.
- Levels of CA125, HE4, ROMA were the highest in high-grade
serous adenocarcinoma. The concentration of CA125 was
1733,2±1841,92 UI/ml, HE4 was 833,2±656,16 pmol/l, ROMA test
was 94,3±8,64%. The concentration of CA125, HE4, ROMA were
different between the histopathological types (p<0,01).
- The concentrations of CA125, HE4, ROMA are valuable in
monitoring the treatment process, specifically as follows: The
concentrations of CA125, HE4, ROMA were different between the
groups before surgery, after surgery, after 3 cycles of chemotherapy
and chemical finish with p value < 0,01.
- CA125, HE4, ROMA levels can predict poor response to treatment
when they rise between treatment courses.
- The concentration of CA125, HE4 decreased in all of stages and the
histopathological types, especially after surgery.
CHAPTER 1: OVERVIEW
1.1. Tumor marker CA125.
Role of CA125 in ovarian cancer diagnosis: CA125 has low
sensitivity especially for early stage disease. Specificity is lower for
premenopausal women. A meta-analysis of 77 studies showed a
sensitivity of CA125 of 78% and specificity of 78%. Another study
found that about 85% of epithelial ovarian cancers had CA125 levels
above 35 U/mL. CA125 levels are usually higher in the serosal than
in mucinous, clear cell, and borderline tumours. CA125 may be
elevated in other malignancies (pancreatic, breast, colon, and lung
cancers) and in benign, physiological states such as pregnancy,
endometriosis, and menstruation. CA125 also plays an important role
in ovarian cancer screening strategies. Four large ovarian cancer
screening trials have been reported in the past decade, including: The
Kentucky Study, the Shizuoka Japan Prospective Study on Breast