**1. Introduction**

Ovarian cancer is one of the most common gynaecologic malignancies that have the highest mortality rate. Ovarian cancer is the third most common [after cervical and corpus uteri] gynaecological malignancy worldwide and it is the most deadly gynaecological malignancy [1]. The disease produces few and nonspecific symptoms early in the course of illness. Consequently about 70% of the cases are diagnosed in the advanced stage [stage 3 and 4] with a 5 year survival of less than 30%. The disease has a good prognosis if diagnosed in the early stages, with a 5 year survival rate in stage 1 disease being 83.4–89.6% [2].

Therefore it is imperative to diagnose the disease early to improve prognosis and reduce mortality.

Diagnosis is usually based on clinical examination followed by transvaginal ultrasonography. Both these methods suffer from low specificity and subjectivity and are thus not recommended for screening.

The differentiation between benign and malignant ovarian disease is often only possible after histological examination of the resected ovarian tissue. It subjects the women to unnecessary surgical procedures which could be avoided if reliable, accurate, noninvasive tests were to become available as a majority of ovarian masses in both premenopausal and postmenopausal women are benign.

This is followed by measurement of serum biomarker levels the most common being CA125, and HE4. Though CA125 is an established biomarker, it has a low specificity and can be elevated in other benign gynaecological conditions and malignancies. 40–50% patients with epithelial ovarian cancer [EOC's] have normal CA125 levels [3].

HE4 is the only other biomarker approved by FDA for monitoring response to treatment and recurrence of disease in EOC. HE4 is a secretory protein of the whey acidic protein [WAP] family. The expression of HE4 is restricted to reproductive tract and respiratory epithelium in normal individuals. HE4 levels are over expressed in EOC tissues and serves as a sensitive and specific serum marker for diagnosis, prognosis and disease recurrence. It is also less likely to be elevated in benign conditions. HE4 levels may also be elevated in other malignancies such as endometrial cancer and pulmonary neoplasms and has been proposed as a biomarker for these conditions [4].
