SMRP and HE4 as Biomarkers for Ovarian Carcinoma When Used Alone and in Combination with CA125 and/or Each Other

Assays measuring tumor antigens in serum have the advantage that they are noninvasive, quick, and relatively inexpensive. Early detection as well as monitoring of disease in treated patients requires high specificity and sensitivity and constant levels of circulating marker unless there is a change in the patient’s clinical status.

CA125 is the present “gold standard” for diagnosis of ovarian carcinoma using serum samples (1–4). However, it is elevated in several nonmalignant conditions, which can lead to false-positive results (5). There is a need for additional markers to improve sensitivity with retained or better specificity, and many new biomarkers have been introduced and continue to be evaluated. Our group has focused on soluble mesothelin-related proteins (SMRP) and on HE4, a protease that is secreted into serum. In immunohistological studies of ovarian cancer samples with little or no detectable CA125 expression, mesothelin and HE4 stood out as the most promising markers, when reactivity with normal tissues was taken into account (6). Other biomarkers in this study included HK4, HK6, OPN, claudin 3, DF3, VEGF, MUC1, and CA19-9.