New hope for ovarian cancer

Xchange newsletter – May 2009

Cancer Research UK lists ovarian cancer as 14th in the table of most commonly diagnosed cancers, and a close second to uterine cancer in all of the gynaecological cancers. It makes up around 4% of all cancers found in women. If detected and treated at an early stage, there is an excellent prognosis. Advanced stage ovarian cancer, the group in which the majority of cases are diagnosed, has a very poor prognosis with a survival rate not much more than 10% [1]. Early diagnosis of this type of cancer is paramount and a new biomarker, human epididymal protein 4 (HE4) could make this a reality.

Assessing the masses

One of the key findings in ovarian cancer is a pelvic mass, which may be malignant or benign [2]. To date, CA125 has been the marker of choice to discriminate between malignant and benign pelvic masses, but by the time a CA125 measurement is of value, the disease is often in an advanced stage. Studies carried out to evaluate CA125 alone as a screening method for early ovarian cancer have been inconclusive. The marker has limited sensitivity and specificity for early stage disease [3]. CA125 is valuable in the differentiation of benign and malignant tumours in postmenopausal women, however, in premenopausal women and in certain other gynaecological conditions (endometriosis, PID, fibroids) there are often elevated levels with no malignancy [2,3,5].

Introducing HE4

There is a recognised need for another marker [4] and one such candidate is HE4. Initially expressed at a cellular level in the developing tumour, HE4 is quickly secreted into the serum. High circulating serum levels of HE4 can be detected at an early stage of the disease.

HE4 can be used to detect epithelial ovarian cancer at both early and late stages. A published study by Moore et al [5] suggests the specificity of HE4 to be 96%, and to have a sensitivity of 64% alone when comparing healthy subjects and cancer patients. This can be compared with the sensitivity of CA125 alone in matched conditions, which is only 24%. Using HE4 and CA125 in combination as paired biomarkers increases the sensitivity of the screening test to 72% [5,6]. Analysis of the pathology of benign tumours linked with serum levels of HE4 and CA125 indicates that the two biomarkers may be of use in identifying the risk of developing a malignant tumour.

The power of two

There is mounting evidence that the use of a dual screening test, utilising both CA125 and HE4 will be able to detect ovarian cancers at an earlier stage, with a greater sensitivity and specificity than previously seen with a single biomarker [3,5,6,7]. The Abbott ARCHITECT HE4 assay* is intended for use in conjunction with the existing ovarian cancer screening marker assay ARCHITECT CA125 II™. The calibration range of the ARCHITECT HE4 assay extends to 1500 pmol/L and sample throughput can reach a maximum of 200/hr [6].

*Currently in development
CA125 II is trademark of Fujirebio Diagnostics, Inc., Malvern PA, USA

[1] www.info.cancerresearchuk.org
[2] www.labtestsonline.org.uk
[3] Havrilesky LJ et al, Gynecol. Oncol (2008), doi: 10.1016/j.ygyno.2008.04.041
[4] Coukos G et al, Ovarian Cancer (2008), doi: 10.1007/978-0-387-68969-2_2
[5] Moore RG et al, Gynecol. Oncol (2008); 108: 402-408
[6] Brochure AN2103/uk Novel Markers “ARCHITECT HE4” 03/09/17
[7] Bast R, Transactions of the American Clinical and Climatological Association
(2004); 115

Cancer cells of ovary. Coloured Scanning Electron Micrograph (SEM)
Two types of cells are seen: some ciliated cells with tufts of cilia (yellow);
abundant secretory cells with microvilli (purple). © Science Photo Library

Ovarian cancer. Coloured computed tomography (CT) scan showing a
huge ovarian cancer (round and green at top centre). The cancer is also
invading the region of the kidneys, which are the bean- shaped areas
(black and yellow) at bottom left and right separated by the spinal column (pink). © Science Photo Library