LPA as a Potential Biomarker for Ovarian and Other Gynecologic Cancers

Abstract & Commentary

Synopsis: Plasma LPA levels may represent a potential biomarker for ovarian cancer and other gynecologic cancers. However, these findings are preliminary and require confirmation in larger studies.

Source: Xu Y, et al. JAMA 1998;280:719-723.

Lysophosphatidic acid (lpa) has been shown to stimulate proliferation of ovarian cancer cells and is present in the ascitic fluid of patients with ovarian cancer. Xu and colleagues at the Cleveland Clinic measured total LPA levels in plasma samples from 48 patients with ovarian cancer, 36 women with other gynecologic cancers, 17 women with benign gynecologic diseases, 11 women with breast cancer, five women with leukemias, and 48 healthy controls. Patients in the ovarian cancer group had significantly higher plasma LPA levels (mean, 8.6 mmol/L; range, 1.0-43.1 mmol/L) compared with the healthy control group (mean, 0.6 mmol/L; range, < 0.1-6.3 mmol/L) (P < 0.001). Elevated plasma LPA levels were detected in nine of 10 patients with stage I ovarian cancer, 24 of 25 patients with stages II-IV ovarian cancer, and 14 of 14 patients with recurrent ovarian cancer. Of 36 patients with other gynecologic malignancies, 33 also showed higher LPA levels (mean, 14.9 mmol/L; range, < 0.1-63.2 mmol/L), compared with healthy controls (P < 0.001). Elevated plasma LPA levels were detected in five of 48 controls, in four of 17 patients with benign gynecologic diseases, and in no women with breast cancer or leukemia. In comparison, among a subset of patients with ovarian cancer, 28 of 47 had elevated CA 125 levels, including two of nine patients with stage I disease. Xu et al conclude that plasma LPA levels might represent a potential biomarker for ovarian cancer and other gynecologic cancers. However, these findings are preliminary and require confirmation in larger studies.

Comment by David M. Gershenson, MD

Epithelial ovarian cancer remains the most lethal gynecologic malignancy. There is no effective screening test for ovarian cancer, as evidenced by the fact that more than 70% of cases are diagnosed after the tumor has already spread beyond the ovary. Although serum CA 125 has been studied, its sensitivity and specificity are suboptimal. In addition, ultrasound lacks specificity—an estimated 40-100 surgeries are required to diagnose one ovarian cancer. Current strategies in the area of screening include algorithms that use both modalities, the use of multiple serum tumor markers, or the longitudinal study of serum CA 125. The findings of this preliminary report suggest that LPA may offer hope as a new marker that may be more sensitive than serum CA 125. The fact that nine of 10 patients with stage I ovarian cancer had elevated LPA levels is most impressive, considering that serum CA 125 is abnormal in only about 50% of stage I ovarian cancers. LPA also appears to have potential as a biomarker in other gynecologic malignancies. However, five of 48 healthy controls and four of 17 patients with benign gynecologic conditions also had elevated LPA levels. The reason for these false-positive findings is obscure. LPA appears to be one of the most promising markers to emerge in a long while. As Xu et al point out, much larger studies are needed to firmly establish its use and role, if any, in early detection of ovarian cancer, monitoring of therapy effects in women with gynecologic malignancies, and in post-treatment surveillance.