Table I

Tumor markers that may have a role in ovarian carcinoma

Tumor markerDescription
CA72-4 or TAG 72Cancer antigen 72 (CA72-4) or tumor-associated glycoprotein 72 (TAG 72) is a glycoprotein surface antigen found in colon, gastric, and ovarian cancer. It is more frequently elevated in mucinous tumors. There are conflicting reports regarding additional sensitivity for detection of ovarian cancer when combined with CA125 compared to CA125 alone (5–7).
M-CSFSerum macrophage colony-stimulating factor (M-CSF) is a cytokine produced constitutively by normal as well as neoplastic ovarian epithelium. Levels are elevated in 68% of patients with ovarian cancer compared to 2.5% of apparently, healthy controls (8). Elevated levels have been found in ovarian cancer patients with normal levels of CA125 (8). While CA125 alone was elevated in 67% of 46 patients with stage I ovarian cancer, CA125 or M-CSF was elevated in 91% (9).
OVX1Monoclonal antibody OVX1 recognizes an antigenic determinant present in ovarian and breast cancer cells (9). A combination of OVX1, M-CSF, and CA125 can detect a greater fraction of patients with stage 1 ovarian cancer than CA125 alone, but this is accompanied by an additive effect on false positives (9). However, the OVX1 radioimmunoassay is highly dependent on sample handling (11).
LPALysophosphatidic acid (LPA) is a bioactive phospholipid with mitogenic and growth factor-like activities that stimulates the proliferation of cancer cells. Plasma LPA may represent a potential biomarker for ovarian and other gynecologic cancers. Elevated plasma LPA levels were detected in 9 of 10 patients with stage I ovarian cancer and all 24 patients with stage II–IV ovarian cancer. In comparison, only 28 of 47 had elevated CA125 levels, including 2 of 9 patients with stage I disease. LPA levels were also elevated in patients with other gynecologic cancers (12).
ProstasinProstasin is a serine protease normally secreted by the prostate gland. It was identified as a biomarker following identification of overexpression of the gene using microarray technology on RNA pooled from ovarian cancer and normal human ovarian surface epithelial cell lines. The combination of CA125 and prostasin in 37 patients with nonmucinous ovarian cancer and 100 control subjects resulted in a sensitivity of 92% (95% CI = 78.1–98.3%) and a specificity of 94% (95% CI = 87.4–97.7%) for detection of ovarian cancer (13).
OsteopontinOsteopontin is another biomarker that has been identified by exploiting gene expression profiling techniques. Plasma levels of osteopontin were significantly higher in 51 patients with epithelial ovarian cancer compared with 107 healthy controls, 46 patients with benign ovarian disease, and 47 patients with other gynecologic cancers (14).
InhibinSerum inhibin is an ovarian product that decreases to nondetectable levels after menopause. However, certain ovarian cancers (mucinous carcinomas and sex cord stromal tumors such as granulosa cell tumors) continue to produce inhibin, which provides a basis for a serum diagnostic test. Available data show that inhibin assays that detect all inhibin forms, i.e. assays that detect the α subunit both as the free form and as an αβ subunit dimer provide the highest sensitivity/specificity characteristics as an ovarian cancer diagnostic test (15).
KallikreinThe human kallikrein gene family currently consists of 15 members that includes prostate-specific antigen (hK3). Preliminary reports indicate that two kallikreins (hK6 and hK10) may be useful serum biomarkers for diagnosis of ovarian (16–18).