VCAM-1 Expression Linked to Poor Survival in Epithelial Ovarian Cancer

Expression of mesothelium vascular cell adhesion molecule-1 (VCAM-1) is associated with poorer overall and progression-free survival in patients with epithelial ovarian cancer, according to a retrospective analysis. VCAM-1 may be related to development of platinum-resistance in this setting.

Most women with epithelial ovarian cancer achieve a remission with a combination of surgical resection and platinum-based chemotherapy, though approximately 80% will experience a recurrence within 24 months of primary therapy’s completion. The time to recurrence has a major impact on prognosis, but “currently no reliable method or biomarker exists to identify patients most likely to recur in short order or those unlikely to respond to primary therapy from the outset,” wrote study authors led by Jill K. Slack-Davis, PhD, of the University of Virginia in Charlottesville.

VCAM-1 is induced by epithelial ovarian tumors and mediates tumor cell invasion, according to earlier research. The new analysis was a retrospective review of 50 advanced-stage epithelial ovarian cancer patients, 30 deemed VCAM-1–positive and 20 VCAM-1–negative. The results were published online ahead of print in Cancer.

After a minimum of 5 years follow-up, patients expressing mesothelium VCAM-1 had a median overall survival of 44 months, compared with 79 months in VCAM-1–negative patients (P = .035). Five-year survival was 55% in negative patients and 37% in VCAM-1–positive patients.

Progression-free survival was also worse in those expressing VCAM-1, at 18 months compared to 67 months in VCAM-1–negative patients (P < .01); this analysis was done in 41 patients for whom progression information was known.

Expression also seemed related to platinum resistance. The median time to develop resistance was 36 months in VCAM-1–positive patients, and it was not yet reached in negative patients (P = .052). “Together, these observations support the notion that mesothelium expression of VCAM-1 at the time of debulking surgery identifies patients who are less likely to respond favorably to standard-of-care treatment and have an unfavorable prognosis,” the authors wrote.

They also conducted a prospective pilot study to test if soluble VCAM-1 levels differ between malignant and benign conditions and whether the soluble form is reflective of mesothelium expression; assessing soluble VCAM-1 could represent a less invasive way to follow this marker. However, the pilot study was small, and was unable to come to a conclusion on the use of soluble VCAM-1. “Moreover, the data indicate a high level of variability in [soluble] VCAM-1 measurements over time that should be considered in the design of future studies,” the authors wrote.

Still, the results of the retrospective analysis present an opportunity to affect management of this malignancy, they wrote. With new agents including VEGF and PARP inhibitors recently approved and others including immunotherapeutics under development, “it would be interesting to know whether VCAM-1–expression patients respond to these classes of drugs,” the authors wrote.