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Cara Hitung ROMA
Cara Hitung ROMA
Ovarian cancer
Back ground
Ovarian cancer is estimated to be the second most common gynaecological cancer and considered
to be the fifth most common cause of cancer related deaths 1. It is characterised by an incident rate
that increases with age and post-menopausal status among women, although it can develop in
woman as young as 15 and up to 65 years of age.
Different types of ovarian cancer exist and are classified based on the cell type of origin through
histopathological determination. The three cell types associated with cancerous ovarian tumours
include[9,10]:
Surface epithelium
Germ cells
Stromal cells
Epithelial ovarian tumours are the most common type of ovarian cancers 2. They develop from the
cells covering the outer surface of the ovaries. Several histological subtypes of epithelial ovarian
cancer have been identified, and can be further described as benign, malignant or borderline [5, 9].
Epithelial ovarian cancer has a poor prognosis. In most cases the disease will not be diagnosed until
the cancerous tumour has spread to other organs and has reached an advanced stage. The
symptoms are vague and non-specific, especially in the early stages2, 5.
Figure 1
Pathological specimen of ovarian carcinoma [3]
Figure 2
A benign tumor of the ovary, discovered during a C-section; this is a 4 cm teratoma[3]
Risk factors
Risk factors for the development of ovarian cancer include2, 10, 11 :
Signs and symptoms associated with ovarian cancer include 2, 8:
Bloating
Pelvic or abdominal pain and discomfort
Difficulty in eating, feeling satiated quickly or loss of appetite
Urgent or frequent urination
Subtle but continuous gastrointestinal problems such as flatulence, nausea and indigestion and
changes in bowel movement habits
Unexplained fatigue
Diagnosis
The detection of ovarian cancer in the early stages is mostly miss-diagnosed because the symptoms
are vague and only diagnosed in the later stages when the cancer has spread to other organs1.
As a work-up to making a diagnosis, the general health of the patient must be determined. In order
to do so, a doctor may request a full blood count, kidney - and liver function tests. The patient’s
clinical history should be determined and a physical examination performed to detect signs of
ovarian cancer. If a growth in the pelvic region is detected and associated symptoms are noticed,
further tests may be done, including imaging testing, laparoscopy, CA-125 and HE4 tumour marker
tests2, 7, 8].
Biopsies are not preferred in cases where ovarian cancer is suspected, since this creates a risk of
spreading the cancerous cells to other organs. The only way to determine for certain if a growth is
cancerous, however, includes removing it for microscopic histopathological examination by a
histopathologist [2]. Either one or both ovaries may be removed. In the case of the latter, it will
result in a pre-menopausal woman experiencing “sudden” menopause [16].
Figure 3 Figure 4
Staging
When the diagnosis of ovarian cancer has been made, a doctor will have to stage the progression of
the cancer, which is done through a surgical procedure. It is important to know the stage of ovarian
cancer development as it is essential in determining the way the treatment is approached.
Ovarian tumour markers such as CA-125 and HE4 are soluble glycoproteins which are detected in
blood samples. They are typically produced by tumour cells in the body in response to a malignancy
or to certain benign conditions. Ovarian tumour markers might not be elevated in the early stages of
the disease. It therefore is essential that tumour markers have a great sensitivity and specificity for
the type of cancerous cells that they detect.
CA-125
In previous years the tumour marker of choice for the diagnosis and monitoring for recurrence of
ovarian tumours after chemotherapy has been Carbohydrate Antigen 125, more commonly known
as CA-125.
CA-125 is not only elevated in ovarian tumours, but also in other non-cancerous conditions such as
endometriosis, menstruation, pregnancy and benign cysts. It was clear that CA-125 was not specific
to tumour of the ovaries and therefore a poor diagnostic test for the detection of the disease [5, 6, 12].
HE4
Human epididymis protein 4 (HE4), also known as WAP-type four disulphide Core 2 (WFDC2) is
normally expressed in the reproductive system and the respiratory tract, but is also commonly found
in patients with epithelial ovarian cancer, and may reach high concentrations in serous and
endometrioid-ovarian carcinomas [5]. It may also be elevated in conditions such as ovarian cysts,
hypertension, congestive heart failure, renal- and liver disease [4].
Neither CA-125 nor HE4 can be considered a diagnostic test for ovarian cancer on their own or
combined. In a comprehensive meta-analysis conducted by Li, Tie, Chang, Wang et. al, 2012) [13], the
following statistics were published on the predictive value of HE4 and CA-125 for the development
of ovarian cancer (OC) and, more specifically, epithelial ovarian cancer (EOC):
OC EOC
HE4 Sensitivity: 0.77 Sensitivity: 0.79
Specificity: 0.88 Specificity: 0.93
CA-125 Sensitivity: 0.73 Sensitivity: 0.77
Specificity: 0.86 Specificity: 0.88
Storage and handle requirements should be noted for reagent, calibrator and quality control
material to ensure stability. Maintaining the correct storage and handling temperature plays an
important role in the stability of these materials.
The preferred sample type for CA-125 and HE4 is serum or EDTA plasma.
The results that are obtained are determined through a calibration curve which is instrument
generated, using a 2-point calibration and a master curve provided with the reagent information.
ROMA is useful in classifying women into high or low risk groups for the development of epithelial
ovarian cancer or finding the latter upon surgery. Since the patient’s menopausal status must be
taken into account, a predictive index (PI) is separately calculated for premenopausal and
postmenopausal patients using two calculations. To calculate the PI, the test values for the CA-125
and HE4 must be entered in the following equation [14, 15]:
PREMENOPAUSAL POSTMENOPAUSAL
Calculation 1: Calculation 2:
PI = -12.0 + (2.38 X LN [HE4]) + (0.0626 X LN [CA-125]) PI = -8.09 + (1.04 X LN [HE4]) + (0.732 X LN [CA -125])
To calculate the ROMA value, the calculated value for the predictive index is inserted into following
equation [14, 15]:
The percentage value obtained from the ROMA calculation indicates the patient’s risk estimation of
having epithelial ovarian cancer presenting with a pelvic mass and related symptoms. The ROMA
index thus allows for patients to be stratified into low- and high risk groups for ovarian cancer pre-
operatively [14, 15].
The percentage risk estimation of epithelial ovarian cancer is indicated in the following table [14]:
Pre-menopausal: Post-menopausal:
LOW RISK of finding < 11.4 % LOW RISK of finding < 29.9 %
epithelial ovarian epithelial ovarian
cancer cancer
HIGH RISK of finding ≥ 11.4 % HIGH RISK of finding ≥ 29.9 %
epithelial ovarian epithelial ovarian
cancer cancer
Treatment
Treatment of the patient diagnosed with ovarian cancer is more focused on improving the quality of
life rather the treatment of the cancer, with the following 3 main goals aimed for [14]:
The average disease-free period for patients with stage III and IV disease is about 18 months. Only
20-30% of stage III and IV cases are long-term survivors [10].
References
[1]. http://www.clinchem.org/content/57/11/1534.full
[2]. http://www.uptodate.com/contents/ovarian-cancer-diagnosis-and-staging-beyond-the-basics
[3]. http://en.wikipedia.org/wiki/Ovarian_cancer
[4]. http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/62137
[5]. http://www.diagnosticpathology.org/content/8/1/11
[6]. http://www.ogscience.org/Synapse/Data/PDFData/3021OGS/ogs-56-234.pdf
[7]. http://www.cancer.net/cancer-types/ovarian-cancer/diagnosis
[8]. http://www.nhs.uk/Conditions/Cancer-of-the-ovary/Pages/Diagnosis.aspx
[9]. http://www.ovarian.org/types_and_stages.php
[10]. http://atlasgeneticsoncology.org/Tumors/OvaryEpithTumID5230.html
[11]. http://ovariancancer.jhmi.edu/ca125qa.cfm
[12]. http://en.wikipedia.org/wiki/CA-125
[13]. http://www.biomedcentral.com/1471-2407/12/258
[14]. http://www.he4test.com/row/patients/monitoring_he4.html
[15]. Roche Cobas Package Insert. HE4 – Human Eipdidymal Protein 4. 2013-11, V7, English
[16]. www.webmd.com/woman/sugical-menopause-estorigen-after-hysterectomy
[17]. Roche Cobas Package Insert.CA 125 II – Cancer Antigen 125. 2014-03, V 17.0, English